Engineered Guide RNAs and Polynucleotides

SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 19, 2022, is named 199235-733601_SL.txt and is 508,120 bytes in size.

BACKGROUND

Payloads that mediate RNA editing can be viable therapies for genetic diseases. However, highly efficacious payloads that can maximize on-target RNA editing while minimizing off-target RNA editing are needed. Moreover, payloads that are capable of facilitating RNA editing for protein knockdown are also needed.

SUMMARY

Disclosed herein are compositions comprising an engineered guide RNA or an engineered polynucleotide encoding the engineered guide RNA. In some embodiments, the engineered guide RNA, upon hybridization to a sequence of a DUX4 target RNA, can form a guide-target RNA scaffold with the sequence of the DUX4 target RNA; formation of the guide-target RNA scaffold substantially forms one or more structural features selected from the group consisting of: a bulge, an internal loop, a hairpin, and a mismatch formed by a base in the engineered guide RNA to a G, a C, or a U in the DUX4 target RNA; and the structural feature may not be present within the engineered guide RNA prior to the hybridization of the engineered guide RNA to the DUX4 target RNA; and upon hybridization of the engineered guide RNA to the sequence of the DUX4 target RNA, the engineered guide RNA can facilitate RNA editing of one or more target adenosines in the sequence of the DUX4 target RNA by an RNA editing entity. In some embodiments, the sequence of the DUX4 target RNA can comprise a translation initiation site, a polyA signal sequence, a splice site, or any combination thereof. In some embodiments, the sequence of the DUX4 target RNA can comprise the polyA signal sequence. In some embodiments, the one or more features can further comprise a mismatch formed by a base in the engineered guide RNA to an A in the DUX4 target RNA. In some embodiments, the DUX4 can be DUX4-FL. In some embodiments, the sequence of the DUX4 target RNA can comprise the polyA signal sequence. In some embodiments, the polyA signal sequence can be in DUX4-FL. In some embodiments, polyA signal sequence can comprise ATTAAA. In some embodiments, any A of the ATTAAA polyA signal sequence can be the target adenosine. In some embodiments, position 0 of ATTAAA can be the target adenosine, wherein position 0 is the first A of ATTAAA at the 5′ end. In some embodiments, the one or more structural features can comprise: a first 6/6 symmetric internal loop at a position selected from the group consisting of: −3, −4, −5, −6, −7, −8, −9, −10, and −11, relative to position 0 of ATTAAA. In some embodiments, the first 6/6 symmetric internal loop can be at position −5 relative to position 0. In some embodiments, the one or more structural features can further comprise a second 6/6 symmetric internal loop at position 33 relative to position 0. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054.In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1054. In some embodiments, the first 6/6 symmetric internal loop is at position −6 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 977. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 977.In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 934. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 934. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1575.In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 internal loop at position 47 relative to position 0, a 5/5 internal loop at position 60 relative to position 0, a 5/5 internal loop at position 73 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1573. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 internal loop at position 45 relative to position 0, a 5/5 internal loop at position 56 relative to position 0, a 5/5 internal loop at position 67 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1569. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1567. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1588. In some embodiments, the first 6/6 symmetric internal loop is at position −9 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 593. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 593. In some embodiments, position 3 of ATTAAA is the target adenosine, wherein position 3 is the second A of ATTAAA from the 5′ end. In some embodiments, the one or more structural features can comprise: a first 6/6 symmetric internal loop at a position selected from the group consisting of: 22, 21, 20, −2, −4, −5, −6, −7, −8, −9, and −10 relative to position 0 of ATTAAA. In some embodiments, the first 6/6 symmetric internal loop is at position 20 relative to position 0. In some embodiments, the one or more structural features can further comprise an A/C mismatch at position 3 relative to position 0. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 8. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 8. In some embodiments, the first 6/6 symmetric internal loop is at position −5 relative to position 0. In some embodiments, the one or more structural features can further comprise a second 6/6 symmetric internal loop at position 33 relative to position 0. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1054. In some embodiments, the first 6/6 symmetric internal loop is at position −6 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 977. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 977. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 45 relative to position 0, a 5/5 symmetric internal loop at position 56 relative to position 0, a 5/5 symmetric internal loop at position 67 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1569. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1567. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 47 relative to position 0, a 5/5 symmetric internal loop at position 60 relative to position 0, a 5/5 symmetric internal loop at position 73 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1573. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1588. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: A/C mismatch at position 3, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1575. In some embodiments, the first 6/6 symmetric internal loop is at position −9 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 593. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 593. In some embodiments, the one or more structural features can comprise: a first 2/2 symmetric bulge at a position selected from the group consisting of: −3, −5, and −7 relative to position 0 of ATTAAA. In some embodiments, the first 2/2 symmetric bulge is at position −5 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: a 2/2 symmetric bulge at position 26 relative to position 0, a 2/2 symmetric bulge at position 42 relative to position 0, a 2/2 symmetric bulge at position 58 relative to position 0, a 2/2 symmetric bulge at position 74 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1545. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1545.In some embodiments, position 4 of ATTAAA is the target adenosine, wherein position 4 is the third A of ATTAAA from the 5′ end. In some embodiments, the one or more structural features can comprise: a first 6/6 symmetric internal loop at a position selected from the group consisting of: 33, −1, −2, −3, −4, −5, −6, −7, −8, −9, −11, and −12 relative to position 0 of ATTAAA. In some embodiments, the first 6/6 symmetric internal loop is at position −1 relative to position 0.

In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1463. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1463. In some embodiments, the first 6/6 symmetric internal loop is at position −3 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1294. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1294. In some embodiments, the first 6/6 symmetric internal loop is at position −5 relative to position 0. In some embodiments, the one or more structural features can further comprise a second 6/6 symmetric internal loop at position 33 relative to position 0. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1054. In some embodiments, the first 6/6 symmetric internal loop is at position −6 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 934. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 934. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 47 relative to position 0, a 5/5 symmetric internal loop at position 60 relative to position 0, a 5/5 symmetric internal loop at position 73 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1573. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1575. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1567. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 45 relative to position 0, a 5/5 symmetric internal loop at position 56 relative to position 0, a 5/5 symmetric internal loop at position 67 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1569. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1588. In some embodiments, the first 6/6 symmetric internal loop is at position −9 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 593. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 593. In some embodiments, position 5 of ATTAAA is the target adenosine, wherein position 5 is the forth A of ATTAAA from the 5′ end. In some embodiments, the one or more structural features can comprise:a first 6/6 symmetric internal loop at a position selected from the group consisting of: 33, 23, −1, −2, −3, −4, −5, −6, −7, −8, −9, −10, and −12 relative to position 0 of ATTAAA. In some embodiments, the first 6/6 symmetric internal loop is at position −1 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1463. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1463. In some embodiments, the first 6/6 symmetric internal loop is at position −5 relative to position 0. In some embodiments, the one or more structural features can further comprise a second 6/6 symmetric internal loop at position 33 relative to position 0. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1054. In some embodiments, the first 6/6 symmetric internal loop is at position −6 relative to position 0. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1575. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1567. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 47 relative to position 0, a 5/5 symmetric internal loop at position 60 relative to position 0, a 5/5 symmetric internal loop at position 73 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1573. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 45 relative to position 0, a 5/5 symmetric internal loop at position 56 relative to position 0, a 5/5 symmetric internal loop at position 67 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1569. In some embodiments, the one or more structural features can further comprise at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. In some embodiments, the engineered guide RNA can comprise at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. In some embodiments, the engineered guide RNA can comprise SEQ ID NO: 1588. In some embodiments, the method can further comprise editing at any A of ATTAAA. In some embodiments, the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 8. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 593. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 934. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 977. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1054. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1294. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1463. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1545. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1567. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1569. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1573. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1575. In some embodiments, the one or more structural features can comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some embodiments, the engineered guide RNA can have at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1588. In some embodiments, the one or more structural features can comprise: a first 6/6 symmetric internal loop, and at least one additional structural feature selected from the group consisting of: a second 6/6 symmetric internal loop, a 5/5 symmetric internal loop, a 4/4 symmetric bulge, a 3/3 symmetric bulge, and a 2/2 symmetric bulge. In some embodiments, the guide-target RNA scaffold can further comprise an A/C mismatch, wherein the cytosine of the A/C mismatch is present in the engineered guide RNA opposite the one or more target adenosines; and wherein the one or more structural features comprise: the first 6/6 symmetric internal loop positioned from position −4 to −8, relative to the A/C mismatch; the second 6/6 symmetric internal loop positioned from position+31 to +35, relative to the A/C mismatch.

In some embodiments, the guide-target RNA scaffold can further comprise an A/C mismatch, wherein the cytosine of the A/C mismatch is present in the engineered guide RNA opposite the one or more target adenosines; and wherein the one or more structural features comprise: the first 6/6 symmetric internal loop at position −6, relative to the A/C mismatch; the second 6/6 symmetric internal loop at position+33, relative to the A/C mismatch. In some embodiments, the first 6/6 symmetric internal loop can comprise the sequence GGAACU on the engineered guide RNA side, and the sequence UUCAGA on the target RNA side.In some embodiments, the second 6/6 symmetric internal loop can comprise the sequence CUGACC on the engineered guide RNA side, and the sequence AGAUUU on the target RNA side. In some embodiments, the one or more structural features can comprise a first 6/6 symmetric internal loop and a second 6/6 symmetric internal loop and wherein each A in the target RNA is base paired to a U in the engineered guide RNA. In some embodiments, the one or more structural features can comprise the bulge. In some embodiments, the bulge can be a symmetric bulge. In some embodiments, the one or more structural features can comprise the bulge. In some embodiments, the bulge can be an asymmetric bulge. In some embodiments, the one or more structural features can comprise the internal loop, wherein the internal loop is a symmetric internal loop. In some embodiments, the one or more structural features can comprise the internal loop. In some embodiments, the internal loop can be an asymmetric internal loop. In some embodiments, the one or more structural features can comprise the mismatch formed by a base in the engineered guide RNA to a G, a C, or a U in the DUX4 target RNA. In some embodiments, the RNA editing entity can comprise ADAR1, ADAR2, ADAR3, or any combination thereof. In some embodiments, the RNA editing of one or more target adenosines can comprise hyper-editing. In some embodiments, the hyper-editing can comprise editing of more than one A in the polyA signal sequence of the DUX4 target RNA. In some embodiments, the internal loop of the engineered guide RNA can comprise any nucleotide in any positional order. In some embodiments, the nucleotide in any positional order is not complementary to their positional counterpart in the DUX 4 target RNA. In some embodiments, the engineered guide RNA or the engineered polynucleotide encoding the engineered guide RNA can be circular. In some embodiments, the engineered guide RNA or the engineered polynucleotide encoding the engineered guide RNA can comprise a U7 hairpin sequence, a SmOPT sequence, or a combination thereof and optionally wherein the U7 hairpin sequence can comprise SEQ ID NO 1591 or 1593 and wherein the SmOPT sequence can comprise SEQ ID NO: 1595. In some embodiments, the DUX4 target RNA can comprise a pre-mRNA transcript of DUX4. In some embodiments, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the pre-mRNA transcripts of DUX4 can have at least one edit in the polyA signal sequence. In some embodiments, at least 80% of the pre-mRNA transcripts of DUX4 can have at least one edit in the polyA signal sequence. In some embodiments, the editing of one or more adenosines can facilitate a mRNA knockdown. In some embodiments, the mRNA knockdown can comprise a knockdown of DUX4 mRNA. In some embodiments, the mRNA knockdown can comprise a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of a mRNA level after RNA editing as compared to a mRNA level before RNA editing. In some embodiments, the mRNA knockdown can be at least 50% of the mRNA level as compared to the mRNA level before RNA editing. In some embodiments, the mRNA knockdown can be at least 70% of the mRNA level as compared to the mRNA level before RNA editing. In some embodiments, the editing of one or more adenosines can facilitate a protein knockdown. In some embodiments, the protein knockdown can comprise a knockdown of DUX4. In some embodiments, the protein knockdown can comprise a knockdown of a protein downstream of DUX4. In some embodiments, the protein downstream of DUX4 can comprise SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2, or any combination thereof. In some embodiments, the protein knockdown can comprise a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein level after RNA editing as compared to the protein level before RNA editing. In some embodiments, the protein knockdown can comprise a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein level in an ADAR expressing cell as compared to a cell comprising an nonfunctional ADAR gene. In some embodiments, the protein knockdown can comprise ADAR-dependent protein knockdown. In some embodiments, the ADAR-dependent protein knockdown can comprise a reduction of at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein level as compared to the protein level before RNA editing. In some embodiments, the engineered guide RNA is an in vitro transcribed (IVT) engineered guide RNA. In some embodiments, the composition can comprise the engineered polynucleotide. In some embodiments, the engineered polynucleotide can be comprised in or on a vector. In some embodiments, the vector can be a viral vector. In some embodiments, the engineered polynucleotide can be encapsidated in the viral vector. In some embodiments, the viral vector can be an adeno-associated viral (AAV) vector or a derivative thereof. In some embodiments, the vector can be a non-viral vector. In some embodiments, the non-viral vector can be a lipid nanoparticle (LNP), a liposome, or a polymer nanoparticle. In some embodiments, the engineered polynucleotide can be a DNA polynucleotide encoding the engineered guide RNA. In some embodiments, the engineered guide RNA can comprise at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 2-SEQ ID NO: 1589. In some embodiments, the engineered guide RNA can comprise a sequence of any one of SEQ ID NO: 2-SEQ ID NO: 1589.

Also described herein are pharmaceutical compositions comprising: a) any of the compositions described above; and b) a pharmaceutically acceptable: excipient, carrier, or diluent.

Also described herein are methods of treating a disease or a condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of any of the compositions described above or the pharmaceutical composition described above.

In some embodiments, the disease or condition can comprise facioscapulohumeral muscular dystrophy (FSHD). In some embodiments, FSHD can comprise Type I FSHD. In some embodiments, FSHD can comprise Type II FSHD. In some embodiments, the administering can comprise parenteral administration, intravenous administration, subcutaneous administration, intrathecal administration, intraperitoneal administration, intramuscular administration, intravascular administration, infusion administration, topical administration, oral administration, inhalation administration, intraduodenal administration, rectal administration, or a combination thereof. In some embodiments, the administration can be oral administration. In some embodiments, the administering can comprise systemic administration.

Also described herein are methods of editing a DUX4 RNA. In some embodiments, the method can comprise contacting the DUX4 RNA with any one of the compositions described above and an RNA editing entity, thereby editing the DUX4 RNA. In some embodiments, the editing can comprise editing at any A position of a polyA tail of the DUX4 RNA. In some embodiments, the DUX4 RNA can comprise a pre-mRNA transcript of DUX4. In some embodiments, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence. In some embodiments, the editing of DUX4 RNA can facilitate a protein knockdown. In some embodiments, the protein knockdown can comprise a knockdown of DUX4.

Also described herein are the compositions described above and the pharmaceutical compositions described above for use as a medicament. In some embodiments, a composition described above or a pharmaceutical composition described above can be for use in the treatment of facioscapulohumeral muscular dystrophy (FSHD). In some embodiments, FSHD can comprise Type I FSHD. In some embodiments, FSHD can comprise Type II FSHD.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

Novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which exemplary principles of the present disclosure are utilized, and the accompanying drawings of which:

FIG. 1 shows a schematic of the double homeobox 4 (DUX4) target, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure.

FIG. 2 shows a schematic of the DMPK target, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure.

FIG. 3 shows a schematic of the PMP22 target, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure.

FIG. 4 shows a schematic of the SOD1 target, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure.

FIG. 6 is a plot showing, on the x-axis, the sequence similarity of the DUX4-targeting engineered guide RNA sequences of the present disclosure to a canonical guide RNA design and, on the y-axis, the edited fraction by an ADAR2 enzyme. These data highlight the diverse sequence space represented by the DUX4-targeting engineered guide RNA sequences of the present disclosure, which have a range of different structural features that drive sequence diversity and which exhibit high on-target editing efficiency.

FIG. 7 shows a schematic of the luciferase and GFP reporter constructs designed to determine expression changes of the reporters fused to mutated DUX4-FL polyA site adenosines.

FIG. 8A shows the viability and transfection efficiencies of LHCN cells after transfection with the luciferase reporters.

FIG. 8B shows the mCherry median fluorescent intensity (MFI) of luciferase reporter transfected LHCN cells.

FIG. 8C shows the luciferase signal normalized to mCherry MFI of the luciferase constructs carrying the mutated or wild type DUX4-FL polyA site adenosines.

FIG. 9A shows the viability and transfection efficiencies of LHCN cells after transfection with the GFP reporters.

FIG. 9B shows the mCherry median fluorescent intensity (MFI) of GFP reporter transfected LHCN cells.

FIG. 9C shows the GFP MFI signal normalized to mCherry MFI of the GFP constructs carrying the mutated or wild type DUX4-FL polyA site adenosines.

FIG. 10 shows editing of an integrated DUX4-luciferase reporter in HEK cells with different guide RNAs.

FIG. 11 shows editing of an integrated DUX4-luciferase reporter in ADAR ½ (1 and 2) knockout HEK cells with different guide RNAs.

DETAILED DESCRIPTION
RNA Editing

RNA editing can refer to a process by which RNA can be enzymatically modified post synthesis at specific nucleosides. RNA editing can comprise any one of an insertion, deletion, or substitution of a nucleotide(s). Examples of RNA editing include chemical modifications, such as pseudouridylation (the isomerization of uridine residues) and deamination (removal of an amine group from cytidine to give rise to uridine, or C-to-U editing or from adenosine to inosine, or A-to-I editing). RNA editing can be used to introduce mutations, correct missense mutations, or edit coding or non-coding regions of RNA to inhibit RNA translation and effect protein knockdown.

Described herein are engineered guide RNAs that facilitate RNA editing by an RNA editing entity (e.g., an adenosine Deaminase Acting on RNA (ADAR)) or biologically active fragments thereof. In some instances, ADARs can be enzymes that catalyze the chemical conversion of adenosines to inosines in RNA. Because the properties of inosine mimic those of guanosine (inosine will form two hydrogen bonds with cytosine, for example), inosine can be recognized as guanosine by the translational cellular machinery. “Adenosine-to-inosine (A-to-I) RNA editing”, therefore, effectively changes the primary sequence of RNA targets. In general, ADAR enzymes share a common domain architecture comprising a variable number of amino-terminal dsRNA binding domains (dsRBDs) and a single carboxy-terminal catalytic deaminase domain. Human ADARs possess two or three dsRBDs. Evidence suggests that ADARs can form homodimer as well as heterodimer with other ADARs when bound to double-stranded RNA, however it can be currently inconclusive if dimerization is needed for editing to occur. The engineered guide RNAs disclosed herein can facilitate RNA editing by any of or any combination of the three human ADAR genes that have been identified (ADARs 1-3). ADARs have a typical modular domain organization that includes at least two copies of a dsRNA binding domain (dsRBD; ADAR1 with three dsRBDs; ADAR2 and ADAR3 each with two dsRBDs) in their N-terminal region followed by a C-terminal deaminase domain. The engineered guide RNAs of the present disclosure facilitate RNA editing by endogenous ADAR enzymes. In some embodiments, exogenous ADAR can be delivered alongside the engineered guide RNAs disclosed herein.

The present disclosure, in some embodiments, provides engineered guide RNAs that facilitate edits at particular regions in a target RNA (e.g., mRNA or pre-mRNA). For example, the engineered guide RNAs disclosed herein can target a coding sequence of an RNA. A target region in a coding sequence of an RNA can be a translation initiation site (TIS). The engineered guide RNAs disclosed herein can target a non-coding sequence of an RNA, for example, a polyadenylation (polyA) signal sequence in the 3′UTR. The engineered guide RNAs disclosed herein can target a splice site. In some cases, a splice site can be present pre-mRNA (prior to processing to remove introns).

The present disclosure, in some embodiments, provides engineered guide RNAs that facilitate edits at multiple adenosines. Hydrolytic deamination of multiple adenosines in an RNA can be referred to as hyper-editing. In some cases, hyper-editing can occur in cis (e.g. in an Alu element) or in trans (e.g. in a target RNA by an engineered guide RNA). In some cases, hyper-editing can comprise editing in the polyA signal sequence of the DUX4-FL target RNA. In some cases, hyper-editing can introduce edits in at least 2 or more nucleotides of a subject target RNA. In some cases, hyper-editing can introduce at least or at most about 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, or at least or at most about 100 edits in a region of a target RNA. In an embodiment, hyper-editing can occur in an untranslated region, translated region, 3′UTR, 5′UTR, or any combinations thereof.

TIS. In some embodiments, the engineered guide RNAs of the present disclosure target the adenosine at a translation initiation site (TIS). The engineered guide RNAs facilitate ADAR-mediated RNA editing of the TIS (AUG) to GUG. This results in inhibition of RNA translation and, thereby, protein knockdown.

Splice site. In some embodiments, the engineered guide RNAs of the present disclosure target an adenosine at a splice site. The engineered guide RNAs facilitate ADAR-mediated RNA editing of an A at a splice site. This can result in mistranslation and/or truncation of a protein encoded by the pre-mRNA molecule and, thereby, protein knockdown.

PolyA Signal Sequence. In some embodiments, the engineered guide RNAs of the present disclosure target one or more adenosines in the polyA signal sequence. In some embodiments, an engineered guide RNA facilitates ADAR-mediated RNA editing of the one or more adenosines in the polyA signal sequence, thereby resulting in disruption of RNA processing and degradation of the target mRNA and, thereby, protein knockdown. In some embodiments, a target can have one or more polyA signal sequences. In these instances, one or more engineered guide RNAs, varying in their respective sequences, of the present disclosure can be multiplexed to target adenosines in the one or more polyA signal sequences. In both cases, the engineered guide RNAs of the present disclosure facilitated ADAR-mediated RNA editing of adenosines to inosines (read as guanosines by cellular machinery) in the polyA signal sequence, resulting in protein knockdown.

Engineered Guide RNAs

Disclosed herein are engineered guide RNAs and engineered polynucleotides encoding the same for site-specific, selective editing of a target RNA via an RNA editing entity or a biologically active fragment thereof. An engineered guide RNA of the present disclosure can comprise latent structures, such that when the engineered guide RNA is hybridized to the target RNA to form a guide-target RNA scaffold, at least a portion of the latent structure manifests as at least a portion of a structural feature as described herein.

An engineered guide RNA as described herein comprises a targeting domain with complementarity to a target RNA described herein. As such, a guide RNA can be engineered to site-specifically/selectively target and hybridize to a particular target RNA, thus facilitating editing of specific nucleotide in the target RNA via an RNA editing entity or a biologically active fragment thereof. The targeting domain can include a nucleotide that is positioned such that, when the guide RNA is hybridized to the target RNA, the nucleotide opposes a base to be edited by the RNA editing entity or biologically active fragment thereof and does not base pair, or does not fully base pair, with the base to be edited. This mismatch can help to localize editing of the RNA editing entity to the desired base of the target RNA. However, in some instances there can be some, and in some cases significant, off target editing in addition to the desired edit.

Hybridization of the target RNA and the targeting domain of the guide RNA produces specific secondary structures in the guide-target RNA scaffold that manifest upon hybridization, which are referred to herein as “latent structures.” Latent structures when manifested become structural features described herein, including mismatches, bulges, internal loops, and hairpins. Without wishing to be bound by theory, the presence of structural features described herein that are produced upon hybridization of the guide RNA with the target RNA configure the guide RNA to facilitate a specific, or selective, targeted edit of the target RNA via the RNA editing entity or biologically active fragment thereof. Further, the structural features in combination with the mismatch described above generally facilitate an increased amount of editing of a target adenosine, fewer off target edits, or both, as compared to a construct comprising the mismatch alone or a construct having perfect complementarity to a target RNA. Accordingly, rational design of latent structures in engineered guide RNAs of the present disclosure to produce specific structural features in a guide-target RNA scaffold can be a powerful tool to promote editing of the target RNA with high specificity, selectivity, and robust activity. FIG. 5 illustrates a target RNA scaffold with exemplary structural features.

Provided herein are engineered guides and polynucleotides encoding the same; as well as compositions comprising said engineered guide RNAs or said polynucleotides. As used herein, the term “engineered” in reference to a guide RNA or polynucleotide encoding the same refers to a non-naturally occurring guide RNA or polynucleotide encoding the same. For example, the present disclosure provides for engineered polynucleotides encoding engineered guide RNAs. In some embodiments, the engineered guide comprises RNA. In some embodiments, the engineered guide comprises DNA. In some examples, the engineered guide comprises modified RNA bases or unmodified RNA bases. In some embodiments, the engineered guide comprises modified DNA bases or unmodified DNA bases. In some examples, the engineered guide comprises both DNA and RNA bases.

In some examples, the engineered guides provided herein comprise an engineered guide that can be configured, upon hybridization to a target RNA molecule, to form, at least in part, a guide-target RNA scaffold with at least a portion of the target RNA molecule, wherein the guide-target RNA scaffold comprises at least one structural feature, and wherein the guide-target RNA scaffold recruits an RNA editing entity and facilitates a chemical modification of a base of a nucleotide in the target RNA molecule by the RNA editing entity.

In some examples, a target RNA of an engineered guide RNA of the present disclosure can be a pre-mRNA or mRNA. In some embodiments, the engineered guide RNA of the present disclosure hybridizes to a sequence of the target RNA. In some embodiments, part of the engineered guide RNA (e.g., a targeting domain) hybridizes to the sequence of the target RNA. The part of the engineered guide RNA that hybridizes to the target RNA is of sufficient complementary to the sequence of the target RNA for hybridization to occur.

A. Targeting Domain

Engineered guide RNAs disclosed herein can be engineered in any way suitable for RNA editing. In some examples, an engineered guide RNA generally comprises at least a targeting sequence that allows it to hybridize to a region of a target RNA molecule. A targeting sequence can also be referred to as a “targeting domain” or a “targeting region”.

In some cases, a targeting domain of an engineered guide allows the engineered guide to target an RNA sequence through base pairing, such as Watson Crick base pairing. In some examples, the targeting sequence can be located at either the N-terminus or C-terminus of the engineered guide. In some cases, the targeting sequence can be located at both termini. The targeting sequence can be of any length. In some cases, the targeting sequence can be at least about: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, or up to about 200 nucleotides in length. In some cases, the targeting sequence can be no greater than about: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, or 200 nucleotides in length. In some examples, an engineered guide comprises a targeting sequence that can be from about 60 to about 500, from about 60 to about 200, from about 75 to about 100, from about 80 to about 200, from about 90 to about 120, or from about 95 to about 115 nucleotides in length. In some examples, an engineered guide RNA comprises a targeting sequence that can be about 100 nucleotides in length.

In some cases, a targeting domain comprises 95%, 96%, 97%, 98%, 99%, or 100% sequence complementarity to a target RNA. In some cases, a targeting sequence comprises less than 100% complementarity to a target RNA sequence. For example, a targeting sequence and a region of a target RNA that can be bound by the targeting sequence can have a single base mismatch.

B. Engineered Guide RNAs Having a Recruiting Domain

In some examples, a subject engineered guide RNA comprises a recruiting domain that recruits an RNA editing entity (e.g., ADAR), where in some instances, the recruiting domain is formed and present in the absence of binding to the target RNA. A “recruiting domain” can be referred to herein as a “recruiting sequence” or a “recruiting region”. In some examples, a subject engineered guide can be configured to facilitate editing of a base of a nucleotide of a polynucleotide of a region of a subject target RNA, modulation expression of a polypeptide encoded by the subject target RNA, or both. In some cases, an engineered guide can be configured to facilitate an editing of a base of a nucleotide or polynucleotide of a region of an RNA by a subject RNA editing entity. In order to facilitate editing, an engineered guide RNA of the disclosure can recruit an RNA editing entity. Various RNA editing entity recruiting domains can be utilized. In some examples, a recruiting domain comprises: Glutamate ionotropic receptor AMPA type subunit 2 (GluR2), APOBEC, or Alu.

In some examples, more than one recruiting domain can be included in an engineered guide of the disclosure. In examples where a recruiting domain can be present, the recruiting domain can be utilized to position the RNA editing entity to effectively react with a subject target RNA after the targeting sequence, for example an antisense sequence, hybridizes to a target RNA. In some cases, a recruiting domain can allow for transient binding of the RNA editing entity to the engineered guide. In some examples, the recruiting domain allows for permanent binding of the RNA editing entity to the engineered guide. A recruiting domain can be of any length. In some cases, a recruiting domain can be from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, up to about 80 nucleotides in length. In some cases, a recruiting domain can be no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, or 80 nucleotides in length. In some cases, a recruiting domain can be about 45 nucleotides in length. In some cases, at least a portion of a recruiting domain comprises at least 1 to about 75 nucleotides. In some cases, at least a portion of a recruiting domain comprises about 45 nucleotides to about 60 nucleotides.

In an embodiments, a recruiting domain comprises a GluR2 sequence or functional fragment thereof. In some cases, a GluR2 sequence can be recognized by an RNA editing entity, such as an ADAR or biologically active fragment thereof. In some embodiments, a GluR2 sequence can be a non-naturally occurring sequence. In some cases, a GluR2 sequence can be modified, for example for enhanced recruitment. In some embodiments, a GluR2 sequence can comprise a portion of a naturally occurring GluR2 sequence and a synthetic sequence.

In some examples, a recruiting domain comprises a GluR2 sequence, or a sequence having at least about 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identity and/or length to: GUGGAAUAGUAUAACAAUAUGCUAAAUGUUGUUAUAGUAUCCCAC (SEQ ID NO: 1). In some cases, a recruiting domain can comprise at least about 80% sequence homology to at least about 10, 15, 20, 25, or 30 nucleotides of SEQ ID NO: 1. In some examples, a recruiting domain can comprise at least about 90%, 95%, 96%, 97%, 98%, or 99% sequence homology and/or length to SEQ ID NO: 1.

Additional, RNA editing entity recruiting domains are also contemplated. In an embodiment, a recruiting domain comprises an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) domain. In some cases, an APOBEC domain can comprise a non-naturally occurring sequence or naturally occurring sequence. In some embodiments, an APOBEC-domain-encoding sequence can comprise a modified portion. In some cases, an APOBEC-domain-encoding sequence can comprise a portion of a naturally occurring APOBEC-domain-encoding-sequence. In another embodiment, a recruiting domain can be from an Alu domain.

Any number of recruiting domains can be found in an engineered guide of the present disclosure. In some examples, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to about 10 recruiting domains can be included in an engineered guide. Recruiting domains can be located at any position of subject guides. In some cases, a recruiting domain can be on an N-terminus, middle, or C-terminus of a polynucleotide. A recruiting domain can be upstream or downstream of a targeting sequence. In some cases, a recruiting domain flanks a targeting sequence of a subject guide. A recruiting sequence can comprise all ribonucleotides or deoxyribonucleotides, although a recruiting domain comprising both ribo- and deoxyribonucleotides can in some cases not be excluded.

C. Engineered Guide RNAs with Latent Structure

In some examples, an engineered guide disclosed herein useful for facilitating editing of a target RNA by an RNA editing entity can be an engineered latent guide RNA. An “engineered latent guide RNA” refers to an engineered guide RNA that comprises latent structure. “Latent structure” refers to a structural feature that substantially forms upon hybridization of a guide RNA to a target RNA. For example, the sequence of a guide RNA provides one or more structural features, but these structural features substantially form only upon hybridization to the target RNA, and thus the one or more latent structural features manifest as structural features upon hybridization to the target RNA. Upon hybridization of the guide RNA to the target RNA, the structural feature is formed and the latent structure provided in the guide RNA is, thus, unmasked.

A double stranded RNA (dsRNA) substrate is formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA. The resulting dsRNA substrate is also referred to herein as a “guide-target RNA scaffold.”

FIG. 5 shows a legend of various exemplary structural features present in guide-target RNA scaffolds formed upon hybridization of a latent guide RNA of the present disclosure to a target RNA. Example structural features shown include an 8/7 asymmetric loop (8 nucleotides on the target RNA side and 7 nucleotides on the guide RNA side), a 2/2 symmetric bulge (2 nucleotides on the target RNA side and 2 nucleotides on the guide RNA side), a 1/1 mismatch (1 nucleotide on the target RNA side and 1 nucleotide on the guide RNA side), a 5/5 symmetric internal loop (5 nucleotides on the target RNA side and 5 nucleotides on the guide RNA side), a 24 bp region (24 nucleotides on the target RNA side base paired to 24 nucleotides on the guide RNA side), and a ⅔ asymmetric bulge (2 nucleotides on the target RNA side and 3 nucleotides on the guide RNA side). Unless otherwise noted, the number of participating nucleotides in a given structural feature is indicated as the nucleotides on the target RNA side over nucleotides on the guide RNA side. Also shown in this legend is a key to the positional annotation of each figure. For example, the target nucleotide to be edited is designated as the 0 position. Downstream (3′) of the target nucleotide to be edited, each nucleotide is counted in increments of +1. Upstream (5′) of the target nucleotide to be edited, each nucleotide is counted in increments of −1. Thus, the example 2/2 symmetric bulge in this legend is at the +12 to +13 position in the guide-target RNA scaffold. Similarly, the ⅔ asymmetric bulge in this legend is at the −36 to −37 position in the guide-target RNA scaffold. As used herein, positional annotation is provided with respect to the target nucleotide to be edited and on the target RNA side of the guide-target RNA scaffold. As used herein, if a single position is annotated, the structural feature extends from that position away from position 0 (target nucleotide to be edited). For example, if a latent guide RNA is annotated herein as forming a ⅔ asymmetric bulge at position −36, then the ⅔ asymmetric bulge forms from −36 position to the −37 position with respect to the target nucleotide to be edited (position 0) on the target RNA side of the guide-target RNA scaffold. As another example, if a latent guide RNA is annotated herein as forming a 2/2 symmetric bulge at position+12, then the 2/2 symmetric bulge forms from the +12 to the +13 position with respect to the target nucleotide to be edited (position 0) on the target RNA side of the guide-target RNA scaffold.

In some examples, the engineered guides disclosed herein lack a recruiting region and recruitment of the RNA editing entity can be effectuated by structural features of the guide-target RNA scaffold formed by hybridization of the engineered guide RNA and the target RNA. In some examples, the engineered guide, when present in an aqueous solution and not bound to the target RNA molecule, does not comprise structural features that recruit the RNA editing entity (e.g., ADAR). The engineered guide RNA, upon hybridization to a target RNA, form with the target RNA molecule, one or more structural features that recruits an RNA editing entity (e.g., ADAR).

In cases where a recruiting sequence can be absent, an engineered guide RNA can be still capable of associating with a subject RNA editing entity (e.g., ADAR) to facilitate editing of a target RNA and/or modulate expression of a polypeptide encoded by a subject target RNA. This can be achieved through structural features formed in the guide-target RNA scaffold formed upon hybridization of the engineered guide RNA and the target RNA. Structural features can comprise any one of a: mismatch, symmetrical bulge, asymmetrical bulge, symmetrical internal loop, asymmetrical internal loop, hairpins, wobble base pairs, or any combination thereof.

Described herein are structural features which can be present in a guide-target RNA scaffold of the present disclosure. Examples of features include a mismatch, a bulge (symmetrical bulge or asymmetrical bulge), an internal loop (symmetrical internal loop or asymmetrical internal loop), or a hairpin (a recruiting hairpin or a non-recruiting hairpin). Engineered guide RNAs of the present disclosure can have from 1 to 50 features. Engineered guide RNAs of the present disclosure can have from 1 to 5, from 5 to 10, from 10 to 15, from 15 to 20, from 20 to 25, from 25 to 30, from 30 to 35, from 35 to 40, from 40 to 45, from 45 to 50, from 5 to 20, from 1 to 3, from 4 to 5, from 2 to 10, from 20 to 40, from 10 to 40, from 20 to 50, from 30 to 50, from 4 to 7, or from 8 to 10 features. In some embodiments, structural features (e.g., mismatches, bulges, internal loops) can be formed from latent structure in an engineered latent guide RNA upon hybridization of the engineered latent guide RNA to a target RNA and, thus, formation of a guide-target RNA scaffold. In some embodiments, structural features are not formed from latent structures and are, instead, pre-formed structures (e.g., a GluR2 recruitment hairpin or a hairpin from U7 snRNA).

A guide-target RNA scaffold is formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA. As disclosed herein, a mismatch refers to a single nucleotide in a guide RNA that is unpaired to an opposing single nucleotide in a target RNA within the guide-target RNA scaffold. A mismatch can comprise any two single nucleotides that do not base pair. Where the number of participating nucleotides on the guide RNA side and the target RNA side exceeds 1, the resulting structure is no longer considered a mismatch, but rather, is considered a bulge or an internal loop, depending on the size of the structural feature. In some embodiments, a mismatch in a guide RNA is to a G, a C, or a U in the DUX4 target RNA. For example, a G in the DUX4 target RNA can mismatch with a G, an A or a U in the guide RNA. In another example, a C in the DUX4 target RNA can mismatch with a C, an A, or a U in the guide RNA. In another example, a U in the DUX4 target RNA can mismatch with a U, a G, or a C in the guide RNA. In some embodiments, a mismatch in a guide RNA is to an A in the DUX4 target RNA. For example, an A in the DUX4 target RNA can mismatch with an A, a G, or a C in the guide RNA. In some embodiments, a mismatch is an A/C mismatch. An A/C mismatch can comprise a C in an engineered guide RNA of the present disclosure opposite an A in a target RNA. An A/C mismatch can comprise an A in an engineered guide RNA of the present disclosure opposite a C in a target RNA. A G/G mismatch can comprise a G in an engineered guide RNA of the present disclosure opposite a G in a target RNA. In some embodiments, a guide RNA of the present disclosure may not have an A/C mismatch and each A of the target RNA is base paired to a U in the engineered guide RNA.

In some embodiments, a mismatch positioned 5′ of the edit site can facilitate base-flipping of the target A to be edited. A mismatch can also help confer sequence specificity. Thus, a mismatch can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

In another aspect, a structural feature comprises a wobble base. A wobble base pair refers to two bases that weakly base pair. For example, a wobble base pair of the present disclosure can refer to a G paired with a U. Thus, a wobble base pair can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

In some cases, a structural feature can be a hairpin. As disclosed herein, a hairpin includes an RNA duplex wherein a portion of a single RNA strand has folded in upon itself to form the RNA duplex. The portion of the single RNA strand folds upon itself due to having nucleotide sequences that base pair to each other, where the nucleotide sequences are separated by an intervening sequence that does not base pair with itself, thus forming a base-paired portion and non-base paired, intervening loop portion. A hairpin can have from 10 to 500 nucleotides in length of the entire duplex structure. The loop portion of a hairpin can be from 3 to 15 nucleotides long. A hairpin can be present in any of the engineered guide RNAs disclosed herein. The engineered guide RNAs disclosed herein can have from 1 to 10 hairpins. In some embodiments, the engineered guide RNAs disclosed herein have 1 hairpin. In some embodiments, the engineered guide RNAs disclosed herein have 2 hairpins. As disclosed herein, a hairpin can include a recruitment hairpin or a non-recruitment hairpin. A hairpin can be located anywhere within the engineered guide RNAs of the present disclosure. In some embodiments, one or more hairpins is proximal to or present at the 3′ end of an engineered guide RNA of the present disclosure, proximal to or at the 5′ end of an engineered guide RNA of the present disclosure, proximal to or within the targeting domain of the engineered guide RNAs of the present disclosure, or any combination thereof.

In some aspects, a structural feature comprises a non-recruitment hairpin. A non-recruitment hairpin, as disclosed herein, does not have a primary function of recruiting an RNA editing entity. A non-recruitment hairpin, in some instances, does not recruit an RNA editing entity. In some instances, a non-recruitment hairpin has a dissociation constant for binding to an RNA editing entity under physiological conditions that is insufficient for binding. For example, a non-recruitment hairpin has a dissociation constant for binding an RNA editing entity at 25° C. that is greater than about 1 mM, 10 mM, 100 mM, or 1 M, as determined in an in vitro assay. A non-recruitment hairpin can exhibit functionality that improves localization of the engineered guide RNA to the target RNA. In some embodiments, the non-recruitment hairpin improves nuclear retention. In some embodiments, the non-recruitment hairpin comprises a hairpin from U7 snRNA. Thus, a non-recruitment hairpin such as a hairpin from U7 snRNA is a pre-formed structural feature that can be present in constructs comprising engineered guide RNA constructs, not a structural feature formed by latent structure provided in an engineered latent guide RNA.

A hairpin of the present disclosure can be of any length. In an aspect, a hairpin can be from about 10-500 or more nucleotides. In some cases, a hairpin can comprise about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500 or more nucleotides. In other cases, a hairpin can also comprise 10 to 20, 10 to 30, 10 to 40, 10 to 50, 10 to 60, 10 to 70, 10 to 80, 10 to 90, 10 to 100, 10 to 110, 10 to 120, 10 to 130, 10 to 140, 10 to 150, 10 to 160, 10 to 170, 10 to 180, 10 to 190, 10 to 200, 10 to 210, 10 to 220, 10 to 230, 10 to 240, 10 to 250, 10 to 260, 10 to 270, 10 to 280, 10 to 290, 10 to 300, 10 to 310, 10 to 320, 10 to 330, 10 to 340, 10 to 350, 10 to 360, 10 to 370, 10 to 380, 10 to 390, 10 to 400, 10 to 410, 10 to 420, 10 to 430, 10 to 440, 10 to 450, 10 to 460, 10 to 470, 10 to 480, 10 to 490, or 10 to 500 nucleotides.

A guide-target RNA scaffold is formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA. As disclosed herein, a bulge refers to the structure substantially formed only upon formation of the guide-target RNA scaffold, where contiguous nucleotides in either the engineered guide RNA or the target RNA are not complementary to their positional counterparts on the opposite strand. The nucleotides in a bulge of the guide RNA can comprise any nucleotide, in any order so long as they are not complementary to their positional counterparts on the target RNA. A bulge can change the secondary or tertiary structure of the guide-target RNA scaffold. A bulge can independently have from 0 to 4 contiguous nucleotides on the guide RNA side of the guide-target RNA scaffold and 1 to 4 contiguous nucleotides on the target RNA side of the guide-target RNA scaffold or a bulge can independently have from 0 to 4 nucleotides on the target RNA side of the guide-target RNA scaffold and 1 to 4 contiguous nucleotides on the guide RNA side of the guide-target RNA scaffold. However, a bulge, as used herein, does not refer to a structure where a single participating nucleotide of the engineered guide RNA and a single participating nucleotide of the target RNA do not base pair—a single participating nucleotide of the engineered guide RNA and a single participating nucleotide of the target RNA that do not base pair is referred to herein as a mismatch. Further, where the number of participating nucleotides on either the guide RNA side or the target RNA side exceeds 4, the resulting structure is no longer considered a bulge, but rather, is considered an internal loop. In some embodiments, the guide-target RNA scaffold of the present disclosure has 2 bulges. In some embodiments, the guide-target RNA scaffold of the present disclosure has 3 bulges. In some embodiments, the guide-target RNA scaffold of the present disclosure has 4 bulges. Thus, a bulge can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

In some embodiments, the presence of a bulge in a guide-target RNA scaffold can position or can help to position ADAR to selectively edit the target A in the target RNA and reduce off-target editing of non-target A(s) in the target RNA. In some embodiments, the presence of a bulge in a guide-target RNA scaffold can recruit or help recruit additional amounts of ADAR. Bulges in guide-target RNA scaffolds disclosed herein can recruit other proteins, such as other RNA editing entities. In some embodiments, a bulge positioned 5′ of the edit site can facilitate base-flipping of the target A to be edited. A bulge can also help confer sequence specificity for the A of the target RNA to be edited, relative to other A(s) present in the target RNA. For example, a bulge can help direct ADAR editing by constraining it in an orientation that yields selective editing of the target A.

A guide-target RNA scaffold is formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA. A bulge can be a symmetrical bulge or an asymmetrical bulge. An asymmetrical bulge is formed when a different number of nucleotides is present on each side of the bulge. For example, an asymmetrical bulge in a guide-target RNA scaffold of the present disclosure can have different numbers of nucleotides on the engineered guide RNA side and the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 1 nucleotide on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the target RNA side of the guide-target RNA scaffold and 1 nucleotide on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 2 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the target RNA side of the guide-target RNA scaffold and 2 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 3 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the target RNA side of the guide-target RNA scaffold and 3 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 4 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 0 nucleotides on the target RNA side of the guide-target RNA scaffold and 4 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 1 nucleotide on the engineered guide RNA side of the guide-target RNA scaffold and 2 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 1 nucleotide on the target RNA side of the guide-target RNA scaffold and 2 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 1 nucleotide on the engineered guide RNA side of the guide-target RNA scaffold and 3 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 1 nucleotide on the target RNA side of the guide-target RNA scaffold and 3 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 1 nucleotide on the engineered guide RNA side of the guide-target RNA scaffold and 4 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 1 nucleotide on the target RNA side of the guide-target RNA scaffold and 4 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 2 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 3 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 2 nucleotides on the target RNA side of the guide-target RNA scaffold and 3 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 2 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 4 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 2 nucleotides on the target RNA side of the guide-target RNA scaffold and 4 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 3 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 4 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical bulge of the present disclosure can be formed by 3 nucleotides on the target RNA side of the guide-target RNA scaffold and 4 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. Thus, an asymmetrical bulge can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

In some cases, a structural feature can be an internal loop. As disclosed herein, an internal loop refers to the structure substantially formed only upon formation of the guide-target RNA scaffold, where nucleotides in either the engineered guide RNA or the target RNA are not complementary to their positional counterparts on the opposite strand and where one side of the internal loop, either on the target RNA side or the engineered guide RNA side of the guide-target RNA scaffold, has 5 nucleotides or more. The nucleotides in an internal loop of the guide RNA can comprise any nucleotide, in any order so long as they are not complementary to their positional counterparts on the target RNA. Where the number of participating nucleotides on both the guide RNA side and the target RNA side drops below 5, the resulting structure is no longer considered an internal loop, but rather, is considered a bulge or a mismatch, depending on the size of the structural feature. An internal loop can be a symmetrical internal loop or an asymmetrical internal loop. Internal loops present in the vicinity of the edit site can help with base flipping of the target A in the target RNA to be edited.

One side of the internal loop, either on the target RNA side or the engineered guide RNA side of the guide-target RNA scaffold, can be formed by from 5 to 150 nucleotides. One side of the internal loop can be formed by 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 120, 135, 140, 145, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, or 1000 nucleotides, or any number of nucleotides therebetween. One side of the internal loop can be formed by 5 nucleotides. One side of the internal loop can be formed by 10 nucleotides. One side of the internal loop can be formed by 15 nucleotides. One side of the internal loop can be formed by 20 nucleotides. One side of the internal loop can be formed by 25 nucleotides. One side of the internal loop can be formed by 30 nucleotides. One side of the internal loop can be formed by 35 nucleotides. One side of the internal loop can be formed by 40 nucleotides. One side of the internal loop can be formed by 45 nucleotides. One side of the internal loop can be formed by 50 nucleotides. One side of the internal loop can be formed by 55 nucleotides. One side of the internal loop can be formed by 60 nucleotides. One side of the internal loop can be formed by 65 nucleotides. One side of the internal loop can be formed by 70 nucleotides. One side of the internal loop can be formed by 75 nucleotides. One side of the internal loop can be formed by 80 nucleotides. One side of the internal loop can be formed by 85 nucleotides. One side of the internal loop can be formed by 90 nucleotides. One side of the internal loop can be formed by 95 nucleotides. One side of the internal loop can be formed by 100 nucleotides. One side of the internal loop can be formed by 110 nucleotides. One side of the internal loop can be formed by 120 nucleotides. One side of the internal loop can be formed by 130 nucleotides. One side of the internal loop can be formed by 140 nucleotides. One side of the internal loop can be formed by 150 nucleotides. One side of the internal loop can be formed by 200 nucleotides. One side of the internal loop can be formed by 250 nucleotides. One side of the internal loop can be formed by 300 nucleotides. One side of the internal loop can be formed by 350 nucleotides. One side of the internal loop can be formed by 400 nucleotides. One side of the internal loop can be formed by 450 nucleotides. One side of the internal loop can be formed by 500 nucleotides. One side of the internal loop can be formed by 600 nucleotides. One side of the internal loop can be formed by 700 nucleotides. One side of the internal loop can be formed by 800 nucleotides. One side of the internal loop can be formed by 900 nucleotides. One side of the internal loop can be formed by 1000 nucleotides. Thus, an internal loop can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

An internal loop can be a symmetrical internal loop or an asymmetrical internal loop. A symmetrical internal loop is formed when the same number of nucleotides is present on each side of the internal loop. For example, a symmetrical internal loop in a guide-target RNA scaffold of the present disclosure can have the same number of nucleotides on the engineered guide RNA side and the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 5 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 6 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 7 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 8 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 8 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 9 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 9 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 10 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 10 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 11 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 11 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 12 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 12 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 13 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 13 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 14 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 14 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 15 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 15 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 20 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 20 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 30 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 30 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 40 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 40 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 50 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 60 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 60 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 70 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 70 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 80 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 80 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 90 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 90 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 100 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 110 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 110 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 120 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 120 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 130 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 130 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 140 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 140 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 150 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 200 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 250 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 250 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 300 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 350 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 350 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 400 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 450 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 450 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 500 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 600 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 600 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 700 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 700 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 800 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 800 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 900 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 900 nucleotides on the target RNA side of the guide-target RNA scaffold. A symmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 1000 nucleotides on the target RNA side of the guide-target RNA scaffold. Thus, a symmetrical internal loop can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

In some embodiments, a symmetrical internal loop can be positioned upstream (5′) of the target A (0 position), downstream (3′) of the target A, or both. In some embodiments, when referring to a location of a structural feature a “−” or negative integer indicates a nucleotide upstream (5′) of the target A or of a specified position (e.g., position 0 ATTAAA), while a positive integer indicates a nucleotide downstream (3′) of the target A, or of a specified position. In some instances, a first symmetrical internal loop can be downstream of the target A and a second symmetrical internal loop can be upstream of the target A. In some cases, a symmetric internal loop can be from position: −1 to −25, −2 to −10, −4 to −8, −5 to −7, −2 to −15, −4 to −20, −8 to −15, or −10 to −22 relative to the target A. In some cases, a symmetric internal loop can be located at position: −25, −24, −23, −22, −21, −20, −19, −18, −17, −16, −15, −14, −13, −12, −11, −10, −9, −8, −7, −6, −5, −4, −3, −2, or −1 relative to the target A. In some cases, a symmetric internal loop can be from position: +1 to +60, +10 to +50, +10 to +40, +20 to +50, +20 to +40, +25 to +45, +31 to +35, +10 to +20, +15 to +30, +25 to +45, or +45 to +60 relative to the target A. In some cases, a symmetric internal loop can be located at position: 1, +2, +3, +4, +5, +6, +7, +8, +9, +10, +11, +12, +13, +14, +15, +16, +17, +18, +19, +20, +21, +22, +23, +24, +25, +26, +27, +28, +29, +30, +31, +32, +33, +34, +35, +36, +37, +38, +39, +40, +41, +42, +43, +44, +45, +46, +47, +48, +49, +50, +51, +52, +53, +54, +55, +56, +57, +58, +59, or +60 relative to the target A. In some cases, a first symmetric internal loop within about: 80 bp, 70 bp, 60 bp, 50 bp, 40 bp, 30 bp, 25 bp, 20 bp, 15 bp, 10 bp, or 5 bp of the 5′ end of the guide RNA, and a second symmetric internal loop within about: 80 bp, 70 bp, 60 bp, 50 bp, 40 bp, 30 bp, 25 bp, 20 bp, 15 bp, 10 bp, or 5 bp of the 3′ end of the guide RNA.

An asymmetrical internal loop is formed when a different number of nucleotides is present on each side of the internal loop. For example, an asymmetrical internal loop in a guide-target RNA scaffold of the present disclosure can have different numbers of nucleotides on the engineered guide RNA side and the target RNA side of the guide-target RNA scaffold.

An asymmetrical internal loop of the present disclosure can be formed by from 5 to 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and from 5 to 150 nucleotides on the target RNA side of the guide-target RNA scaffold, wherein the number of nucleotides is the different on the engineered side of the guide-target RNA scaffold target than the number of nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by from 5 to 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and from 5 to 1000 nucleotides on the target RNA side of the guide-target RNA scaffold, wherein the number of nucleotides is the different on the engineered side of the guide-target RNA scaffold target than the number of nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 6 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 7 nucleotides on the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 7 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 8 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 8 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 9 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 9 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 10 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 10 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 7 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the target RNA side of the guide-target RNA scaffold and 7 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 8 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the target RNA side of the guide-target RNA scaffold and 8 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 9 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the target RNA side of the guide-target RNA scaffold and 9 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 10 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 6 nucleotides on the target RNA side of the guide-target RNA scaffold and 10 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 8 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the target RNA side of the guide-target RNA scaffold and 8 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 9 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the target RNA side of the guide-target RNA scaffold and 9 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 10 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 7 nucleotides on the target RNA side of the guide-target RNA scaffold and 10 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 8 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 9 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 8 nucleotides on the target RNA side of the guide-target RNA scaffold and 9 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 8 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 10 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 8 nucleotides on the target RNA side of the guide-target RNA scaffold and 10 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 9 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold and 10 nucleotides internal loop the target RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 9 nucleotides on the target RNA side of the guide-target RNA scaffold and 10 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 5 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 50 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 50 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 100 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 100 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 150 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 5 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 150 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 200 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 200 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 300 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 300 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 400 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 400 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 500 nucleotides on the target RNA side of the guide-target RNA scaffold and 1000 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. An asymmetrical internal loop of the present disclosure can be formed by 1000 nucleotides on the target RNA side of the guide-target RNA scaffold and 500 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold. Thus, an asymmetrical internal loop can be a structural feature formed from latent structure provided by an engineered latent guide RNA.

As disclosed herein, a “base paired (bp) region” refers to a region of the guide-target RNA scaffold in which bases in the guide RNA are paired with opposing bases in the target RNA. Base paired regions can extend from one end or proximal to one end of the guide-target RNA scaffold to or proximal to the other end of the guide-target RNA scaffold. Base paired regions can extend between two structural features. Base paired regions can extend from one end or proximal to one end of the guide-target RNA scaffold to or proximal to a structural feature. Base paired regions can extend from a structural feature to the other end of the guide-target RNA scaffold. In some embodiments, a base paired region has from from 1 bp to 100 bp, from 1 bp to 90 bp, from 1 bp to 80 bp, from 1 bp to 70 bp, from 1 bp to 60 bp, from 1 bp to 50 bp, from 1 bp to 45 bp, from 1 bp to 40 bp, from 1 bp to 35 bp, from 1 bp to 30 bp, from 1 bp to 25 bp, from 1 bp to 20 bp, from 1 bp to 15 bp, from 1 bp to 10 bp, from 1 bp to 5 bp, from 5 bp to 10 bp, from 5 bp to 20 bp, from 10 bp to 20 bp, from 10 bp to 50 bp, from 5 bp to 50 bp, at least 1 bp, at least 2 bp, at least 3 bp, at least 4 bp, at least 5 bp, at least 6 bp, at least 7 bp, at least 8 bp, at least 9 bp, at least 10 bp, at least 12 bp, at least 14 bp, at least 16 bp, at least 18 bp, at least 20 bp, at least 25 bp, at least 30 bp, at least 35 bp, at least 40 bp, at least 45 bp, at least 50 bp, at least 60 bp, at least 70 bp, at least 80 bp, at least 90 bp, at least 100 bp.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 8 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 8 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 10 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 10 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 21 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 14 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 21 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 14 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 21 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 21 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 15 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 21 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 15 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 21 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 22 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 17 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 22 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 17 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 22 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 23 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 24 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 23 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 24 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 5 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 23 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 72 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 72 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 1 nucleotide mismatch formed 3 nucleotides downstream (5′) from the target A, and a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 7 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 6 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 20 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 34 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 48 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 62 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 76 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1538 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 7 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 6 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 20 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 34 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 48 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 62 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 76 nucleotides downstream(3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1538 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 7 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 6 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 20 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 34 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 48 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 62 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 76 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 3 nucleotide symmetric bulge formed 6 nucleotides upstream (5′) from the target A, a 3 nucleotide symmetric bulge formed 7 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 22 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 37 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 52 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1539 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 3 nucleotide symmetric bulge formed 6 nucleotides upstream (5′) from the target A, a 3 nucleotide symmetric bulge formed 7 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 22 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 37 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 52 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1539 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 3 nucleotide symmetric bulge formed 6 nucleotides upstream (5′) from the target A, a 3 nucleotide symmetric bulge formed 7 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 22 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 37 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 52 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 67 nucleotides downstream(3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 5 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 10 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 26 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 42 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 58 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 74 nucleotides downstream(3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1545 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 5 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 10 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 26 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 42 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 58 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 74 nucleotides downstream(3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1545 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 5 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 10 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 26 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 42 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 58 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 74 nucleotides downstream(3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 3 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 14 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 32 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 50 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 68 nucleotides downstream(3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1552 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 3 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 14 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 32 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 50 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 68 nucleotides downstream(3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1552 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 2 nucleotide symmetric bulge formed 3 nucleotides upstream (5′) from the target A, a 2 nucleotide symmetric bulge formed 14 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 32 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 50 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 68 nucleotides downstream(3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 61 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 77 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1566 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 61 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 77 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1566 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 61 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 77 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 54 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 63 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 72 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1567 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 54 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 63 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 72 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1567 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 54 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 63 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 72 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 65 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1568 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 65 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1568 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 45 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 65 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 45 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 56 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 67 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1569 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 45 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 56 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 67 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1569 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 45 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 56 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 67 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 57 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 77 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1570 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 57 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 77 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1570 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 57 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 77 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 58 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1571 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 58 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1571 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 58 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 59 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 71 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1572 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 59 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 71 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1572 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 47 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 59 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 71 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 47 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 60 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 73 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1573 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 47 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 60 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 73 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1573 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 47 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 60 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 73 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 61 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 73 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1574 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 61 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 73 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1574 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 61 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 73 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 62 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1575 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 62 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1575 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 62 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 63 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1576 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 63 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1576 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 49 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 63 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 49 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 64 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1577 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 49 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 64 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1577 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 49 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 64 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 65 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1578 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 65 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1578 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 65 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 66 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1579 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 66 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1579 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 66 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1580 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1580 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 51 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 67 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 51 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 68 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1581 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 51 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 68 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1581 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 51 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 68 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1582 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1582 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 69 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 70 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1583 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 70 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1583 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 70 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 71 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1584 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 71 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1584 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 53 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 71 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 53 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 72 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1585 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 53 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 72 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1585 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 5 nucleotide internal symmetric loop formed 53 nucleotides downstream (3′) from the target A, and a 5 nucleotide internal symmetric loop formed 72 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 73 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1586 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 73 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1586 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 2 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 2 nucleotide symmetric bulge formed 73 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 74 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1587 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 74 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1587 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 3 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 3 nucleotide symmetric bulge formed 74 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1588 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A. In some cases, an engineered guide RNA of the present disclosure to a target DUX4 RNA has a sequence of SEQ ID NO: 1588 and, the guide-target RNA scaffold formed upon hybridization of said engineered guide RNA to the target DUX4 RNA comprises a 6 nucleotide internal symmetric loop formed 6 nucleotides upstream (5′) from the target A, a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed 33 nucleotides downstream (3′) from the target A, a 4 nucleotide symmetric bulge formed 55 nucleotides downstream (3′) from the target A, and a 4 nucleotide symmetric bulge formed 75 nucleotides downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 1 nucleotide mismatch formed downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed at the target A, and a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, and one 6 nucleotide internal symmetric loop formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, and two 6 nucleotide internal symmetric loop(s) formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, and three 6 nucleotide internal symmetric loop(s) formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, and four 6 nucleotide internal symmetric loop(s) formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and two 2 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and three 2 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and four 2 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and five 2 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and two 3 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and three 3 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and four 3 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and two 4 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and three 4 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and four 4 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and two 5 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 6 nucleotide internal symmetric loop formed upstream (5′) from the target A, a 1 nucleotide mismatch formed downstream (3′) from the target A, a 6 nucleotide internal symmetric loop formed downstream (3′) from the target A, and three 5 nucleotide symmetric bulges formed downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 2 nucleotide symmetric bulge upstream (5′) from the target A and four 2 nucleotide symmetric bulges downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 2 nucleotide symmetric bulge upstream (5′) from the target A and five 2 nucleotide symmetric bulges downstream (3′) from the target A.

In some cases, the structural feature formed upon hybridization of an engineered guide RNA of the present disclosure to a target RNA comprises a 2 nucleotide symmetric bulge upstream (5′) from the target A and six 2 nucleotide symmetric bulges downstream (3′) from the target A.

D. Additional Engineered Guide RNA Components

The present disclosure provides for engineered guide RNAs with additional structural features and components. For example, an engineered guide RNA described herein can be circular. In another example, an engineered guide RNA described herein can comprise a U7, an SmOPT sequence, or a combination of both.

In some cases, an engineered guide RNA can be circularized. In some cases, an engineered guide RNA provided herein can be circularized or in a circular configuration. In some aspects, an at least partially circular guide RNA lacks a 5′ hydroxyl or a 3′ hydroxyl. In some embodiments, a circular engineered guide RNA can comprise a guide RNA from any one of SEQ ID NOs: 2-1589.

In some examples, an engineered guide RNA can comprise a backbone comprising a plurality of sugar and phosphate moieties covalently linked together. In some examples, a backbone of an engineered guide RNA can comprise a phosphodiester bond linkage between a first hydroxyl group in a phosphate group on a 5′ carbon of a deoxyribose in DNA or ribose in RNA and a second hydroxyl group on a 3′ carbon of a deoxyribose in DNA or ribose in RNA.

In some embodiments, a backbone of an engineered guide RNA can lack a 5′ reducing hydroxyl, a 3′ reducing hydroxyl, or both, capable of being exposed to a solvent. In some embodiments, a backbone of an engineered guide can lack a 5′ reducing hydroxyl, a 3′ reducing hydroxyl, or both, capable of being exposed to nucleases. In some embodiments, a backbone of an engineered guide can lack a 5′ reducing hydroxyl, a 3′ reducing hydroxyl, or both, capable of being exposed to hydrolytic enzymes. In some instances, a backbone of an engineered guide can be represented as a polynucleotide sequence in a circular 2-dimensional format with one nucleotide after the other. In some instances, a backbone of an engineered guide can be represented as a polynucleotide sequence in a looped 2-dimensional format with one nucleotide after the other. In some cases, a 5′ hydroxyl, a 3′ hydroxyl, or both, can be joined through a phosphorus-oxygen bond. In some cases, a 5′ hydroxyl, a 3′ hydroxyl, or both, can be modified into a phosphoester with a phosphorus-containing moiety.

As described herein, an engineered guide can comprise a circular structure. An engineered polynucleotide can be circularized from a precursor engineered polynucleotide. Such a precursor engineered polynucleotide can be a precursor engineered linear polynucleotide. In some cases, a precursor engineered linear polynucleotide can be a precursor for a circular engineered guide RNA. For example, a precursor engineered linear polynucleotide can be a linear mRNA transcribed from a plasmid, which can be configured to circularize within a cell using the techniques described herein. A precursor engineered linear polynucleotide can be constructed with domains such as a ribozyme domain and a ligation domain that allow for circularization when inserted into a cell. A ribozyme domain can include a domain that is capable of cleaving the linear precursor RNA at specific sites (e.g., adjacent to the ligation domain). A precursor engineered linear polynucleotide can comprise, from 5′ to 3′: a 5′ ribozyme domain, a 5′ ligation domain, a circularized region, a 3′ ligation domain, and a 3′ ribozyme domain. In some cases, a circularized region can comprise a guide RNA described herein. In some cases, the precursor polynucleotide can be specifically processed at both sites by the 5′ and the 3′ ribozymes, respectively, to free exposed ends on the 5′ and 3′ ligation domains. The free exposed ends can be ligation competent, such that the ends can be ligated to form a mature circularized structure. For instance, the free ends can include a 5′-OH and a 2′, 3′-cyclic phosphate that are ligated via RNA ligation in the cell. The linear polynucleotide with the ligation and ribozyme domains can be transfected into a cell where it can circularize via endogenous cellular enzymes. In some cases, a polynucleotide can encode an engineered guide RNA comprising the ribozyme and ligation domains described herein, which can circularize within a cell. Circular guide RNAs are described in PCT/US2021/034301, which is incorporated by reference in its entirety.

An engineered polynucleotide as described herein (e.g., a circularized guide RNA) can include spacer domains. As described herein, a spacer domain can refer to a domain that provides space between other domains. A spacer domain can be used to between a region to be circularized and flanking ligation sequences to increase the overall size of the mature circularized guide RNA. Where the region to be circularized includes a targeting domain as described herein that is configured to associate to a target sequence, the addition of spacers can provide improvements (e.g. increased specificity, enhanced editing efficiency, etc.) for the engineered polynucleotide to the target polynucleotide, relative to a comparable engineered polynucleotide that lacks a spacer domain. In some instances, the spacer domain is configured to not hybridize with the target RNA. In some embodiments, a precursor engineered polynucleotide or a circular engineered guide, can comprise, in order of 5′ to 3′: a first ribozyme domain; a first ligation domain; a first spacer domain; a targeting domain that can be at least partially complementary to a target RNA, a second spacer domain, a second ligation domain, and a second ribozyme domain. In some cases, the first spacer domain, the second spacer domain, or both are configured to not bind to the target RNA when the targeting domain binds to the target RNA.

The compositions and methods of the present disclosure provide engineered polynucleotides encoding for guide RNAs that are operably linked to a portion of a small nuclear ribonucleic acid (snRNA) sequence. The engineered polynucleotide can include at least a portion of a small nuclear ribonucleic acid (snRNA) sequence. The U7 and U1 small nuclear RNAs, whose natural role is in spliceosomal processing of pre-mRNA, have for decades been re-engineered to alter splicing at desired disease targets. Replacing the first 18 nt of the U7 snRNA (which naturally hybridizes to the spacer element of histone pre-mRNA) with a short targeting (or antisense) sequence of a disease gene, redirects the splicing machinery to alter splicing around that target site. Furthermore, converting the wild type U7 Sm-domain binding site to an optimized consensus Sm-binding sequence (SmOPT) can increase the expression level, activity, and subcellular localization of the artificial antisense-engineered U7 snRNA. Many subsequent groups have adapted this modified U7 SmOPT snRNA chassis with antisense sequences of other genes to recruit spliceosomal elements and modify RNA splicing for additional disease targets.

An snRNA is a class of small RNA molecules found within the nucleus of eukaryotic cells. They are involved in a variety of important processes such as RNA splicing (removal of introns from pre-mRNA), regulation of transcription factors (7SK RNA) or RNA polymerase II (B2 RNA), and maintaining the telomeres. They are always associated with specific proteins, and the resulting RNA-protein complexes are referred to as small nuclear ribonucleoproteins (snRNP) or sometimes as snurps. There are many snRNAs, which are denominated U1, U2, U3, U4, U5, U6, U7, U8, U9, and U10.

The snRNA of the U7 type is normally involved in the maturation of histone mRNA. This snRNA has been identified in a great number of eukaryotic species (56 so far) and the U7 snRNA of each of these species should be regarded as equally convenient for this disclosure.

Wild-type U7 snRNA includes a stem-loop structure, the U7-specific Sm sequence, and a sequence antisense to the 3′ end of histone pre-mRNA.

In addition to the SmOPT domain, U7 comprises a sequence antisense to the 3′ end of histone pre-mRNA. When this sequence is replaced by a targeting sequence that is antisense to another target pre-mRNA, U7 is redirected to the new target pre-mRNA. Accordingly, the stable expression of modified U7 snRNAs containing the SmOPT domain and a targeting antisense sequence has resulted in specific alteration of mRNA splicing. While AAV-2/1 based vectors expressing an appropriately modified murine U7 gene along with its natural promoter and 3′ elements have enabled high efficiency gene transfer into the skeletal muscle and complete dystrophin rescue by covering and skipping mouse Dmd exon 23, the engineered polynucleotides as described herein (whether directly administered or administered via, for example, AAV vectors) can facilitate editing of target RNA by a deaminase.

The engineered polynucleotide can comprise at least in part an snRNA sequence. The snRNA sequence can be U1, U2, U3, U4, U5, U6, U7, U8, U9, or a U10 snRNA sequence.

In some instances, an engineered polynucleotide that comprises at least a portion of an snRNA sequence (e.g. an snRNA promoter, an snRNA hairpin, and the like) can have superior properties for treating or preventing a disease or condition, relative to a comparable polynucleotide lacking such features. For example, as described herein an engineered polynucleotide that comprises at least a portion of an snRNA sequence can facilitate exon skipping of an exon at a greater efficiency than a comparable polynucleotide lacking such features. Further, as described herein an engineered polynucleotide that comprises at least a portion of an snRNA sequence can facilitate an editing of a base of a nucleotide in a target RNA (e.g. a pre-mRNA or a mature RNA) at a greater efficiency than a comparable polynucleotide lacking such features. Promoters and snRNA components are described in PCT/US2021/028618, which is incorporated by reference in its entirety.

Disclosed herein are engineered RNAs comprising (a) an engineered guide RNA as described herein, and (b) a U7 snRNA hairpin sequence, a SmOPT sequence, or a combination thereof. In some embodiments, the U7 hairpin comprises a human U7 Hairpin sequence, or a mouse U7 hairpin sequence. In some cases, a human U7 hairpin sequence comprises TAGGCTTTCTGGCTTTTTACCGGAAAGCCCCT (SEQ ID NO: 1590 or RNA: UAGGCUUUCUGGCUUUUUACCGGAAAGCCCCU (SEQ ID NO: 1591). In some cases, a mouse U7 hairpin sequence comprises CAGGTTTTCTGACTTCGGTCGGAAAACCCCT (SEQ ID NO: 1592 or RNA: CAGGUUUUCUGACUUCGGUCGGAAAACCCCU SEQ ID NO: 1593). In some embodiments, the SmOPT sequence has a sequence of AATTTTTGGAG (SEQ ID NO: 1594 or RNA: AAUUUUUGGAG SEQ ID NO: 1595). In some embodiments, a guide RNA from any one of SEQ ID NOs: 2-1589 can comprise a guide RNA comprising a U7 hairpin sequence (e.g., a human or a mouse U7 hairpin sequence), an SmOPT sequence, or a combination thereof. In some cases, a combination of a U7 hairpin sequence and a SmOPT sequence can comprise a SmOPT U7 hairpin sequence, wherein the SmOPT sequence is linked to the U7 sequence. In some cases, a U7 hairpin sequence, an SmOPT sequence, or a combination thereof is downstream (e.g., 3′) of the engineered guide RNA disclosed herein.

Also disclosed herein are promoters for driving the expression of a guide RNA disclosed herein. In some cases, the promoters for driving expression can be 5′ to the guide RNA sequence disclosed herein. In some cases, a promoter can comprise a U1 promoter, a U7 promoter, a U6 promoter or any combination thereof. In some cases, a promoter can comprise a CMV promoter. In some cases, a U7 promoter, or a U6 promoter can be a mouse U7 promoter, or a mouse U6 promoter. In some cases, a U1 promoter, a U7 promoter, or a U6 promoter can be a human U1 promoter, a human U7 promoter, or a human U6 promoter. In some cases, a human U6 promoter can comprise a sequence with at least about: 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to:

- GAGGGCCTATTTCCCATGATTCCTTCATATTTGCATATACGATACAAGGCTGTTA GAGAGATAATTAGAATTAATTTGACTGTAAACACAAAGATATTAGTACAAAATA CGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTTT AAAATGGACTATCATATGCTTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTT ATATATCTTGTGGAAAGGACGAAACACC (SEQ ID NO: 1596). In some cases, a mouse U6 promoter can comprise a sequence with at least about: 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to:
- GTACTGAGTCGCCCAGTCTCAGATAGATCCGACGCCGCCATCTCTAGGCCCGCGC CGGCCCCCTCGCACAGACTTGTGGGAGAAGCTCGGCTACTCCCCTGCCCCGGTTA ATTTGCATATAATATTTCCTAGTAACTATAGAGGCTTAATGTGCGATAAAAGACA GATAATCTGTTCTTTTTAATACTAGCTACATTTTACATGATAGGCTTGGATTTCTA TAAGAGATACAAATACTAAATTATTATTTTAAAAAACAGCACAAAAGGAAACTC ACCCTAACTGTAAAGTAATTGTGTGTTTTGAGACTATAAATATCCCTTGGAGAAA AGCCTTGTTTG (SEQ ID NO: 1597). In some cases, a human U7 promoter can comprise a sequence with at least about: 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to: TTAACAACATAGGAGCTGTGATTGGCTGTTTTCAGCCAATCAGCACTGACTCATT TGCATAGCCTTTACAAGCGGTCACAAACTCAAGAAACGAGCGGTTTTAATAGTCT TTTAGAATATTGTTTATCGAACCGAATAAGGAACTGTGCTTTGTGATTCACATAT CAGTGGAGGGGTGTGGAAATGGCACCTTGATCTCACCCTCATCGAAAGTGGAGT TGATGTCCTTCCCTGGCTCGCTACAGACGCACTTCCGC (SEQ ID NO: 1598). In some cases, a mouse U7 promoter can comprise a sequence with at least about: 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to:
- TTAACAACATAGGAGCTGTGATTGGCTGTTTTCAGCCAATCAGCACTGACTCATT TGCATAGCCTTTACAAGCGGTCACAAACTCAAGAAACGAGCGGTTTTAATAGTCT TTTAGAATATTGTTTATCGAACCGAATAAGGAACTGTGCTTTGTGATTCACATAT CAGTGGAGGGGTGTGGAAATGGCACCTTGATCTCACCCTCATCGAAAGTGGAGT TGATGTCCTTCCCTGGCTCGCTACAGACGCACTTCCGC (SEQ ID NO: 1599). In some cases, a human U1 promoter can comprise a sequence with at least about: 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to:
- TAAGGACCAGCTTCTTTGGGAGAGAACAGACGCAGGGGCGGGAGGGAAAAAGG GAGAGGCAGACGTCACTTCCTCTTGGCGACTCTGGCAGCAGATTGGTCGGTTGAG TGGCAGAAAGGCAGACGGGGACTGGGCAAGGCACTGTCGGTGACATCACGGAC AGGGCGACTTCTATGTAGATGAGGCAGCGCAGAGGCTGCTGCTTCGCCACTTGCT GCTTCGCCACGAAGGGAGTTCCCGTGCCCTGGGAGCGGGTTCAGGACCGCTGAT CGGAAGTGAGAATCCCAGCTGTGTGTCAGGGCTGGAAAGGGCTCGGGAGTGCGC GGGGCAAGTGACCGTGTGTGTAAAGAGTGAGGCGTATGAGGCTGTGTCGGGGCA GAGCCCGAAGATCTC (SEQ ID NO: 1600). In some cases, a CMV promoter can comprise a sequence with at least about: 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to:

(SEQ ID NO: 1601)

ATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACG

GGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTAC

GGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGA

CGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCA

AGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACT

TGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTT

TTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTC

CAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAAT

CAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAAT

GGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTTTAG

TGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGACCTCCAT

AGAAGACACCGGGACCGATCCAGCCTCCGGACTCTAGAGGATCGAACC.

Targets and Methods of Treatment

The present disclosure provides for compositions of engineered guide RNAs or engineered polynucleotides encoding guide RNAs and methods of use thereof, such as methods of treatment. In some embodiments, the engineered polynucleotides of the present disclosure encode guide RNAs targeting a coding sequence of RNA (e.g., a TIS) or a non-coding sequence of RNA (e.g., a polyA signal sequence). In some embodiments, the present disclosure provides compositions or more than one engineered polynucleotides of encoding more than one engineered guide RNAs targeting the TIS and the polyA sequence. The engineered guide RNAs disclosed herein facilitate ADAR-mediated RNA editing of adenosines in the TIS, the polyA sequence, or both. In some embodiments, engineered guide RNAs disclosed herein can be screened by in vitro and in vivo methods to determine their ability to facilitate ADAR mediated RNA editing of adenosines in a target RNA. In some cases, a screening method can comprise cell based reporter assay as described herein.

DUX4. The present disclosure provides for engineered guide RNAs that facilitate RNA editing of DUX4-FL to knockdown expression of DUX4-FL mRNA and DUX4-activated genes, and hence DUX4 activity. Facioscapulohumeral muscular dystrophy (FSHD) is a rare neuromuscular disease characterized by progressive skeletal muscle weakness and wasting with significant heterogeneity in phenotypic severity and age of onset. FSHD affects mostly the face (facio), shoulder girdle (scapula), and upper arm (humeral) regions of the body. As the disease progresses, muscles of the upper arms, the legs, and the postural muscles in the back loose mass and strength. Patients often first present with weakness of the face and periscapular muscles, eventually resulting in the inability to raise their arms above shoulder height, make facial expressions, or even close their eyes. In about 20% of the patients with FSHD, paraspinal muscle weakness is debilitating enough to result in patients becoming wheelchair-bound. FSHD is one of the most prevalent adult muscular dystrophies caused by an epigenetic derepression of the subtelomeric D4Z4 microsatellite array on chromosome 4q. This epigenetic derepression leads to hypomethylation in the distal-most D4Z4 unit and misexpression of the DUX4 gene in skeletal muscle. There are two subtypes of FSHD—FSHD1 and FSHD2. FSHD1 accounts for 95% of FSHD cases and is associated with the pathogenic contraction of D4Z4 microsatellite repeats, while FSHD2 accounts for 5% of the FSHD cases and is contraction-independent but associated with mutations in the chromatin regulator gene SMCHD1. The mutations for both FSHD1 and FSHD2 result in derepression of D4Z4 array and DUX4 mRNA misexpression. Said DUX4 mutations are autosomal dominant in ⅔ of FSHD1 patients and is prevalent in 1:8,000-12,000 (˜16,000-38,000 patients in the US). DUX4 (double homeobox 4) is a germline transcription factor and its misexpression in muscle activates the expression of a broad set of genes (DUX4-activated genes), many involved in stem and germ cell biology. Some known DUX4-activated genes include MBD3L2, TRIM43, PRAMEF12, ZSCAN, and LEUTX. Although physical therapy, pain management, and surgery can alleviate some of the disabilities associated with FSHD, these treatments are not curative, and none of them address the underlying cause of the disease pathology. While healthy subjects generate a non-toxic splice form of DUX4 mRNA that lacks the C-term transactivation domain of DUX4 (referred to as DUX4-S for short), affected subjects produce a toxic splice form of DUX4 mRNA (referred to as DUX4-FL for full length) leading to expression of a toxic form of the DUX4 protein in muscle. Although various pharmaceutical and cell-based intervention approaches are being explored to treat FSHD, these generally offer little to no therapeutic benefit based on results from clinical trials. To develop a more targeted form of treatment, approaches that reduce muscle-specific DUX4-FL expression and DUX4-mediated toxicity have become attractive goals of FSHD therapy. Indeed, genetic treatments that target the root cause of the disease (e.g., DUX4) are expected to lead to a more effective or far-reaching therapeutic effect. The exact amount of DUX4 inhibition required for effective therapy is currently unknown, but data from clinically affected and asymptomatic FSHD patients support the idea that any reduction in DUX4-FL mRNA expression will have a therapeutic benefit. In some embodiments, the present disclosure provides compositions of engineered guide RNAs that target DUX4 and facilitate ADAR-mediated RNA editing of DUX4, specifically, DUX4-FL to mediate DUX4-FL knockdown. In some embodiments, the engineered guide RNAs of the present disclosure target a coding sequence in DUX4-FL. For example, the coding sequence can be a translation initiation site (TIS) (AUG) of DUX4 and the engineered guide RNA can facilitate ADAR-mediated RNA editing of AUG to GUG. In some embodiments, the engineered guide RNAs of the present disclosure target a splice site in DUX4 pre-mRNA. In some embodiments, the engineered guide RNAs of the present disclosure target a non-coding sequence in DUX4. The non-coding sequence can be a polyA signal sequence (ATTAAA) in the pLAM region and the engineered guide RNA can facilitate ADAR-mediated RNA editing of one or more adenosines in the polyA signal sequence of DUX4. RNA editing of this polyA signal sequence reduces polyadenylation and genetic excision of the DUX4-FL polyA sequence results in DUX4-FL mRNA knockdown and DUX4-FL protein knockdown. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target more than one polyA signal sequences in DUX4. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target the TIS and one or more polyA signal sequences in DUX4.

In some embodiments, a target tissue for a guide RNA targeting DUX4 can comprise a muscle. In some cases, a muscle can comprise a muscle of the face, an arm muscle, a neck muscle, a shoulder muscle, a thigh muscle, a hip muscle, an abdominal muscle, a back muscle, a foot muscle, a hand muscle, or any combination thereof. In some cases, a muscle can comprise an orbicularis oculi, an orbicularis oris, a risorius, a zygomaticus major and minor, a biceps brachii, a triceps brichii, a trapezius, a rhomboids, a levator scapulae, a latissimus dorsi, a pectorals major, a pelvic girdle muscles, an abdominal muscles, a tibialis anterior, or any combination thereof. In some cases, a muscle of the face can comprise an occipitofrontalis muscle, a orbicularis oculi muscle, a temporalis muscle, a buccinator muscle, a masseter muscle, a mentalis muscle, a depressor labii inferioris muscle, a orbicularis oris muscle, a levator anguli oris muscle, a levator labii superioris muscle, a depressor anguli oris muscle, a levator labii superioris alaeque nasi muscle, zygomaticus major and minor muscle, a orbicularis oculi muscle, a corrugator supercilii muscle, or a risorius muscle. In some cases, a neck muscle can comprise an omohyoid muscle, a platysma muscle, a sternohyoid muscle, a sternocleidomastoid muscle, a levator scapulae muscle, a scalene muscle, a trapezius muscle, a semispinalis capitis muscle, a serratus posterior superior muscle, or any combination thereof. In some cases, shoulder muscle can comprise a deltoid muscle, a supraspinatus muscle, a rhomboids muscle, an infraspinatus muscle, a teres minor muscle, a teres major muscle, a pectoralis major muscle, a pectoralis minor, a serratus anterior muscle, or any combination thereof. In some cases, an arm muscle can comprise a triceps brachii muscle, a biceps brachii muscle, a brachialis muscle, a brachioradialis muscle, a carpal muscle, an extensor digitorum muscle, a extensor indicis muscle, an extensor digiti minimi muscle, a flexor digitorum superficialis muscle, a flexor digitorum profundus muscle, flexor pollicis longus muscle, extensor pollicis longus muscle, extensor pollicis brevis muscle, abductor pollicis longus muscle, a thenar muscles muscle, an adductor pollicis muscle, a hypothenar muscles muscle, a lumbricales muscle, a dorsal interossei muscle, a palmar interossei muscle, or any combination thereof. In some cases, a hip muscle can comprise a tensor fasciae muscle, a gluteus minimus muscle, a gluteus maximus muscle, a gluteus medius muscle, a piriformis muscle, a obturator internus muscle, or any combination thereof. In some cases, an abdominal muscle can comprise a pyramidalis muscle, a rectus abdominus muscle, an external oblique muscle, an internal oblique muscle, a transversus abdominis muscle, or any combination thereof. In some cases, a back muscle can comprise a trapezius muscle, a rhomboids muscle, a latissimus dorsi muscle, an erector spinae muscle, a multifidus muscle, a quadratus lumborum muscle, or any combination thereof. In some cases, a leg muscle can comprise a vastus lateralis muscle, a vastus medialis muscle, a vastus intermedius muscle, a rectus femoris muscle, a biceps femoris muscle, a semimembranosus muscle, a semitendinosus muscle, a gastrocnemius muscle, a soleus muscle, a plantaris muscle, or any combination thereof. In some cases, a foot muscle can comprise an abductor hallucis muscle, a tibialis anterior muscle, an extensor digitorum longus muscle, a flexor digitorum longus muscle, a fibularis longus muscle, a fibularis tertius muscle, a fibularis brevis muscle, or any combination thereof.

In some embodiments, a target cell for a guide RNA targeting DUX4 can comprise a somatic (e.g., a muscle cell) or a gamete cell. For example, a somatic cell can comprise a cell of an internal organ, the skin, a muscle, a bone, a blood cell, a connective tissue cell, or any combination thereof. In some cases, a somatic cell can comprise a muscle cell. In some cases, a muscle cell can comprise a skeletal muscle cell, a cardiac muscle cell, a smooth muscle cell, or a combination thereof. In some cases, a muscle cell can comprise a myocyte, a myofibril, a myoblast, a cardiomyocyte, or any combination thereof.

The engineered guide RNAs of the present disclosure facilitated ADAR-mediated RNA editing of DUX4, thereby, affecting reporter protein knockdown. In some embodiments, the engineered guide RNAs of the present disclosure facilitated ADAR-mediated RNA editing of from 1 to 100% of a target adenosine. The engineered guide RNAs of the present disclosure can facilitate from 40 to 90% editing of a target adenosine. In some embodiments, the engineered guide RNAs of the present disclosure can facilitate at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 100%, from 5 to 20%, from 20 to 40%, from 40 to 60%, from 60 to 80%, from 80 to 100%, from 60 to 80%, from 70 to 90%, or up to 90% or more RNA editing of a target adenosine. Optionally, additionally, the engineered guide RNAs of the present disclosure can facilitate these levels of on-target RNA editing while maintaining less than 10% editing of an off-target adenosine. Optionally, additionally, the engineered guide RNAs of the present disclosure can facilitate these levels of on-target RNA editing while maintaining less than less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, or 0% editing of an off-target adenosine.

In some embodiments, the DUX4 RNA comprises a pre-mRNA transcript of DUX4. In some embodiments, an engineered guide RNA of the present disclosure can facilitate editing of at least one edit in the polyA signal sequence the pre-mRNA transcript of DUX4. In some cases, at least 40%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence. In some cases, at least 80%, of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence. In some cases, 1% to 10%, 10% to 20%, 20% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% to 90%, 90% to 100%, 20% to 40%, 30% to 50%, 40% to 60%, 50% to 70%, 60% to 80%, 20% to 50%, or 30% to 60% of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence.

In some embodiments, a mutation in the polyA signal sequence (ATTAAA) in the pLAM region of DUX4-FL results in a DUX4 mRNA knockdown, a DUX4 protein knockdown, or both. As RNA, the polyA signal sequence corresponds to the sequence AUUAAA. In some cases, the polyA signal sequence (AUUAAA) can be mutated to AUUAAG; AUUAGA; AUUGAA; GUUAAA; or GUUGGG. In some cases, an engineered guide RNA disclosed herein can facilitate ADAR-mediated RNA editing of the unmodified polyA signal sequence (AUUAAA) to AUUAAG; AUUAGA; AUUGAA; GUUAAA; or GUUGGG. In some instances, ADAR-mediated RNA editing of the unmodified polyA signal sequence to AUUAAG; AUUAGA; AUUGAA; GUUAAA; or GUUGGG results in a DUX4 mRNA knockdown, a DUX4 protein knockdown, or both.

In some embodiments, an engineered guide disclosed herein can facilitate ADAR-mediated RNA editing of one or more adenosines in the non-coding polyA signal sequence (ATTAAA) in the pLAM region of DUX4. In some cases, a method of editing DUX4 RNA can comprise contacting the DUX4 RNA with a engineered guide disclosed herein and an RNA editing entity. In some cases, the method can comprise editing the non-coding polyA signal sequence. As RNA, the polyA signal sequence corresponds to the sequence AUUAAA. The corresponding positions for each “A” in the polyA signal site sequence (AUUAAA) are denoted as 0, 3, 4, and 5 from left to right. In some cases, editing the polyA signal site sequence can comprise editing the polyA signal site at any A. In some cases, editing can comprise editing from about: 20% to about 95%, 30% to about 95%, 40% to about 95%, 44% to about 91%, 60% to about 95%, or 80% to about 91% of any A position in the polyA tail. In some cases, an engineered guide RNA for targeting the DUX4 polyA signal site sequence at position “0” can comprise a sequence with at least: 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identity and/or length to SEQ ID NO: 1575, 593, 1573, 934, 1569, 1567, 851, 1211, 1571, 937, 1574, 1570, 1566, 1117, 906, 1572, 1104, 352, 512, 1587, 375, 1588, 977, 642, 1236, 1584, 252, 394, 482, 1585, 291, 356, 1054, 1581, 1103, 502, 769, 408, 1586, 1008, 737, 985, 679, 727, 1578, 365, 1580, 487, 1098, or 976. In some cases, editing can comprise editing from about: 20% to about 85%, 30% to about 85%, 40% to about 85%, 50% to about 66%, 40% to about 70%, or 60% to about 66% of the A at position “0” in the polyA tail. In some cases, an engineered guide RNA for targeting the DUX4 polyA signal site sequence at position “3” can comprise a sequence with at least: 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identity and/or length to SEQ ID NO: 1573, 1588, 1545, 1575, 1569, 1584, 1572, 1567, 1570, 1587, 1574, 625, 1571, 874, 17, 1585, 757, 1581, 1538, 8, 1002, 1566, 486, 1552, 505, 635, 606, 884, 1054, 880, 1411, 1568, 871, 1580, 1539, 14, 892, 1116, 15, 1586, 593, 10, 977, 1578, 1579, 747, 1577, 748, 873, or 494. In some cases, editing can comprise editing from about: 20% to about 95%, 30% to about 95%, 40% to about 95%, 76% to about 91%, 60% to about 80%, or 80% to about 91% of the A at position “3” in the polyA tail. In some cases, an engineered guide RNA for targeting the DUX4 polyA signal site sequence at position “4” can comprise a sequence with at least: 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identity and/or length to SEQ ID NO: 1575, 1573, 1567, 1569, 1570, 1566, 1572, 1587, 1571, 1574, 1584, 1588, 1054, 1586, 1585, 1581, 1578, 1580, 934, 72, 1582, 1066, 1183, 1577, 967, 1568, 930, 566, 1463, 1294, 1293, 1391, 1579, 1583, 944, 815, 1168, 593, 594, 694, 1576, 1193, 1051, 1212, 806, 1059, 1374, 195, 358, or 1296. In some cases, editing can comprise editing from about: 20% to about 85%, 30% to about 85%, 40% to about 85%, 54% to about 77%, 50% to about 60%, or 60% to about 77% of the A at position “4” in the polyA tail. In some cases, an engineered guide RNA for targeting the DUX4 polyA signal site sequence at position “5” can comprise a sequence with at least: 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identity and/or length to SEQ ID NO: 1575, 1573, 1569, 1574, 1570, 1572, 1567, 1587, 1566, 1571, 1588, 72, 1586, 1584, 1581, 1578, 1585, 1582, 1580, 1183, 1568, 1066, 1391, 1168, 1293, 1577, 1054, 566, 1579, 930, 694, 944, 195, 1583, 815, 1576, 1051, 1411, 24, 1163, 935, 680, 1212, 594, 1185, 1463, 1058, 810, 392, or 1104. In some cases, editing can comprise editing from about: 20% to about 85%, 30% to about 85%, 40% to about 85%, 44% to about 70%, 50% to about 60%, or 60% to about 70% of the A at position “5” in the polyA tail.

In some embodiments, an engineered guide RNA disclosed herein for targeting DUX4 can comprise a structural feature that is formed in a guide-target RNA scaffold. In some cases, the structural feature comprises a symmetrical internal loop formed by 6 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 6 nucleotides on the target RNA side of the guide-target RNA scaffold. In some cases, the internal loop can start 6 nucleotides upstream (5′) of the target A (0 position) of the target RNA sequence. In some cases, an engineered guide RNA can comprise two or more 6 nucleotide symmetrical internal loops. In some cases, one symmetrical internal loop can be upstream (5′) of the target A (0 position) and one symmetrical internal loop can be downstream (3′) of the target A. In some cases, the structural feature comprises a mismatch formed by 1 nucleotide on the engineered guide RNA side of the guide-target RNA scaffold target and 1 nucleotide on the target RNA side of the guide-target RNA scaffold. In some cases, the mismatch is a A/C mismatch. In some instances, the A/C mismatch comprises the C in an engineered guide RNA of the present disclosure opposite an A in a target RNA. In some cases, the mismatch may be at the target A (0 position) or 3 or 5 nucleotides downstream (3′) from the target A. In some cases, the structural feature comprises a symmetrical bulge formed by 4 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 4 nucleotides on the target RNA side of the guide-target RNA scaffold. In some cases, the structural feature comprises a symmetrical bulge formed by 2 nucleotides on the engineered guide RNA side of the guide-target RNA scaffold target and 2 nucleotides on the target RNA side of the guide-target RNA scaffold. In some instances, a symmetrical bulge is downstream (3′) from the target A.

Assays for Measuring Efficacious Engineered gRNAs Targeting DUX4

In some embodiments, the engineered guide RNAs of the present disclosure facilitate ADAR-mediated RNA editing of DUX4. In some embodiments, ADAR-mediated RNA editing of DUX4 can result in a knockdown (e.g., a reduction) of protein levels, a knockdown in mRNA levels, or both. In some cases, a knockdown of protein levels can be of DUX4 or of a protein downstream of DUX4. In some cases, a knockdown of mRNA levels can be of DUX4 or of a protein downstream of DUX4. In some instances, the knockdown of protein levels and/or mRNA levels is an ADAR dependent knockdown.

In some embodiments, an assay is used to determine the efficacy of a guide RNA disclosed herein. In some cases, an assay can comprise measuring RNA editing, mRNA levels, or protein levels in a cell. In some cases, an assay can comprise measuring RNA editing, mRNA levels, or protein levels in a cell before and after a treatment with a guide RNA disclosed herein. In some cases, cells can be sampled in a time course assay. In some cases, a cell can comprise a cell with a functional ADAR gene. In some cases, a cell can comprise a cell with a nonfunctional ADAR gene. For example, a cell can comprise a truncated or mutated ADAR gene or a cell can comprise a deleted ADAR gene. In some cases, an assay can be used to compare editing levels, levels of mRNA, or levels of protein, in a cell with a functional copy of an ADAR gene and in a cell without a functional ADAR gene. In some cases, the reduction of mRNA or protein levels in the cell can be identified as ADAR dependent reduction in mRNA or protein levels. Protein levels in a cell can be measured by any standard technique, for example a Western Blot. mRNA levels in a cell can be measured by any standard technique, for example by Real-Time Quantitative Reverse Transcription PCR, or droplet digital PCR. In some cases, protein levels can be determined by a functional assay specific to a protein of interest. For example, an assay can be used to determine the amount of a protein by an enzymatic assay measuring the enzyme kinetics of the protein.

In some embodiments, a guide RNA disclosed herein can facilitate ADAR dependent knockdown of mRNA levels or protein levels of 1 to 100%. In some cases, a guide RNA disclosed herein can facilitate ADAR dependent knockdown of mRNA levels or protein levels from 1% to 10%, from 10% to 20%, from 20% to 30%, from 30% to 40%, from 40% to 50%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from 80% to 90%, from 90% to 100%, from 20% to 40%, from 30% to 50%, from 40% to 60%, from 50% to 70%, from 60% to 80%, from 20% to 50%, from 30% to 60%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% as compared to a cell before treatment with the guide RNA. In some cases, ADAR dependent knockdown of mRNA levels or protein levels can be compared between a cell comprising a functional copy of ADAR and a cell comprising a nonfunctional copy of ADAR.

In some embodiments, the engineered guide RNAs of the present disclosure facilitate ADAR-mediated RNA editing of DUX4-FL, which results in knockdown of protein levels. The knockdown in protein levels is quantitated as a reduction in expression of the DUX4-FL protein. The engineered guide RNAs of the present disclosure can facilitate from 1% to 100% DUX4-FL protein knockdown. The engineered guide RNAs of the present disclosure can facilitate from 1% to 10%, from 10% to 20%, from 20% to 30%, from 30% to 40%, from 40% to 50%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from 80% to 90%, from 90% to 100%, from 20% to 40%, from 30% to 50%, from 40% to 60%, from 50% to 70%, from 60% to 80%, from 20% to 50%, from 30% to 60%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% DUX4-FL protein knockdown. In some embodiments, the engineered guide RNAs of the present disclosure facilitate from 30% to 60% DUX4-FL protein knockdown. Protein knockdown (e.g., DUX4-FL knockdown) can be measured by an assay comparing a sample or subject treated with the engineered guide RNA to a control sample or subject not treated with the engineered guide RNA. In some cases, protein knockdown can be measured by comparing the amount of the protein present in a sample or subject before a treatment with a guide RNA disclosed herein and comparing to the amount of the protein after the treatment.

In some embodiments, ADAR-mediated RNA editing of DUX4-FL, results in knockdown of downstream protein levels of one or more proteins downstream of DUX4. In some instances, a knockdown of a protein downstream of DUX4 can be used to determine the reduction of DUX-4 protein levels. In some cases, a downstream protein of DUX4 comprises SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2. The knockdown in protein levels of a downstream protein of DUX4 can be quantitated as a reduction in expression of the SLC34A2 protein, the LEUTX protein, the ZSCAN4 protein, the PRAMEF12 protein, the TRIM43 protein, the DEFB103 protein, or the MBD3L2 protein. The engineered guide RNAs of the present disclosure can facilitate from 1% to 10%, from 10% to 20%, from 20% to 30%, from 30% to 40%, from 40% to 50%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from 80% to 90%, from 90% to 100%, from 20% to 40%, from 30% to 50%, from 40% to 60%, from 50% to 70%, from 60% to 80%, from 20% to 50%, from 30% to 60%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% protein knockdown of SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, MBD3L2 or of another protein downstream of DUX4. In some embodiments, increased editing of the DUX4 RNA by the guide RNA is measured in an assay. In some cases, the increased editing comprises an increase in a protein knockdown of DUX4 and/or of a protein downstream of DUX4. In some cases, the assay can comprise measuring the level of a protein in a sample before and after treatment with a guide RNA described herein. In some cases, the assay can comprise measuring the level of a protein in a sample that is not treated with a guide RNA and measuring the protein in a sample that is treated with a guide RNA described herein.

In some embodiments, the engineered guide RNAs of the present disclosure facilitate ADAR-mediated RNA editing of DUX4, which results in knockdown of mRNA levels. The knockdown in mRNA levels is quantitated as a reduction in expression of the DUX4 mRNA transcript protein. The engineered guide RNAs of the present disclosure can facilitate a 1% to 100% decrease of DUX4 mRNA. The engineered guide RNAs of the present disclosure can facilitate a decrease of: 1% to 10%, 10% to 20%, 20% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% to 90%, 90% to 100%, 20% to 40%, 30% to 50%, 40% to 60%, 50% to 70%, 60% to 80%, 20% to 50%, or 30% to 60% of DUX4 mRNA. The engineered guide RNAs of the present disclosure can facilitate a decrease of: at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of DUX4 mRNA. The engineered guide RNAs of the present disclosure can facilitate a decrease of at least 50%, or at least 70% of DUX4 mRNA. In some embodiments, the engineered guide RNAs of the present disclosure facilitate a decrease of 50% to 75% of DUX4 mRNA. DUX4 (e.g., DUX4-FL) mRNA levels can be measured by an assay comparing a sample or subject treated with the engineered guide RNA to a control sample or subject not treated with the engineered guide RNA.

In some embodiments, the engineered guide RNAs of the present disclosure facilitate ADAR-mediated RNA editing of DUX4, which results in knockdown of mRNA levels of proteins downstream of DUX4. In some cases, a protein downstream of DUX4 can comprise SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2. In some cases, a reduction in the expression of the mRNA of SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2 can indicate a reduction in the expression of DUX4. The engineered guide RNAs of the present disclosure can facilitate a 1% to 100% decrease of SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2 mRNA. The engineered guide RNAs of the present disclosure can facilitate a decrease of: 1% to 10%, 10% to 20%, 20% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% to 90%, 90% to 100%, 20% to 40%, 30% to 50%, 40% to 60%, 50% to 70%, 60% to 80%, 20% to 50%, or 30% to 60% of SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2 mRNA. The engineered guide RNAs of the present disclosure can facilitate a decrease of: at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2 mRNA. SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2. mRNA levels can be measured by an assay comparing a sample or subject treated with the engineered guide RNA to a control sample or subject not treated with the engineered guide RNA.

DMPK. The present disclosure provides for engineered guide RNAs that facilitate RNA editing DMPK to knockdown expression of myotonic dystrophy protein kinase. Myotonic dystrophy (DM1) is a rare neuromuscular disease characterized by progressive muscular weakness and an inability to relax muscles (myotonia), predominantly distal skeletal muscles. Genetic causes of DM1 include expansion of CTG repeats in the 3′UTR of the DMPK gene, causing protein aggregates and subsequent muscle wasting. Severity is linked to age of onset and size of the CTG repeat region. Said DMPK mutations are autosomal dominant and is prevalent in 1:2,300 (˜140,000 patients in the US). Target cell types are skeletal and cardiac muscle cells. In some embodiments, the present disclosure provides compositions of engineered guide RNAs that target DMPK and facilitated ADAR-mediated RNA editing of DMPK. In some embodiments, the engineered guide RNAs of the present disclosure target a coding sequence in DMPK. For example, the coding sequence can be a translation initiation site (TIS) (AUG) of DMPK and the engineered guide RNA can facilitate ADAR-mediated RNA editing of AUG to GUG. In some embodiments, the engineered guide RNAs of the present disclosure target a splice site in DMPK pre-mRNA. In some embodiments, the engineered guide RNAs of the present disclosure target a non-coding sequence in DMPK. The non-coding sequence can be a polyA signal sequence and the engineered guide RNA can facilitate ADAR-mediated RNA editing of one or more adenosines in the polyA signal sequence of DMPK. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target more than one polyA signal sequences in DMPK. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target the TIS and one or more polyA signal sequences in DMPK. The engineered guide RNAs of the present disclosure facilitated ADAR-mediated RNA editing of DMPK, thereby, effecting protein knockdown.

PMP22. The present disclosure provides for engineered guide RNAs that facilitate RNA editing of PMP22 to knockdown expression of peripheral myelin protein-22 (PMP22). Charcot-Marie-Tooth Syndrome (CMT1A) is the most common genetically-driven peripheral neuropathy, characterized by progressive distal muscle atrophy, sensory loss and foot/hand deformities. Genetic causes of CMT1A include PMP22 gene duplication leading to peripheral nerve dysmyelination and poor nerve conduction. Said PMP22 mutations are autosomal dominant and prevalence is in 1:7,500 (˜42,000 patients in the US). Target cell types are Schwann cells. In some embodiments, the present disclosure provides compositions of engineered guide RNAs that target PMP22 and facilitated ADAR-mediated RNA editing of PMP22. In some embodiments, the engineered guide RNAs of the present disclosure target a coding sequence in PMP22. For example, the coding sequence can be a translation initiation site (TIS) (AUG) of PMP22 and the engineered guide RNA can facilitate ADAR-mediated RNA editing of AUG to GUG. In some embodiments, the engineered guide RNAs of the present disclosure target a splice site in PMP22 pre-mRNA. In some embodiments, the engineered guide RNAs of the present disclosure target a non-coding sequence in PMP22. The non-coding sequence can be a polyA signal sequence and the engineered guide RNA can facilitate ADAR-mediated RNA editing of one or more adenosines in the polyA signal sequence of PMP22. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target more than one polyA signal sequences in PMP22. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target the TIS and one or more polyA signal sequences in PMP22. The engineered guide RNAs of the present disclosure facilitated ADAR-mediated RNA editing of PMP22, thereby, effecting protein knockdown.

SOD1. The present disclosure provides for engineered guide RNAs that facilitate RNA editing of SOD1 to knockdown expression of the superoxide dismutase enzyme. Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by death of motor neurons and loss of voluntary muscle movement. While the exact cause of ALS is unknown, gain-of-function mutations in SOD1 account for ˜20% of familiar ALS and 2% of spontaneous ALS. Said SOD1 mutations are autosomal dominant and have a prevalence of 2:100,000 (<1,000 patients in US). Target cell types are motor neurons. In some embodiments, the present disclosure provides compositions of engineered guide RNAs that target SOD1 and facilitated ADAR-mediated RNA editing of SOD1. In some embodiments, the engineered guide RNAs of the present disclosure target a coding sequence in SOD1. For example, the coding sequence can be a translation initiation site (TIS) (AUG) of SOD1 and the engineered guide RNA can facilitate ADAR-mediated RNA editing of AUG to GUG. In some embodiments, the engineered guide RNAs of the present disclosure target a splice site in SOD1 pre-mRNA. In some embodiments, the engineered guide RNAs of the present disclosure target a non-coding sequence in SOD1. The non-coding sequence can be a polyA signal sequence and the engineered guide RNA can facilitate ADAR-mediated RNA editing of one or more adenosines in the polyA signal sequence of SOD1. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target more than one polyA signal sequences in SOD1. In some embodiments, engineered guide RNAs of the present disclosure can be multiplexed to target the TIS and one or more polyA signal sequences in SOD1. The engineered guide RNAs of the present disclosure facilitated ADAR-mediated RNA editing of SOD1, thereby, effecting protein knockdown.

An engineered guide RNA of the present disclosure can be used in a method of treating a disorder in a subject in need thereof. For example, an engineered guide RNA disclosed herein can be used to treat facioscapulohumeral muscular dystrophy and/or myotonic dystrophy. A disorder can be a disease, a condition, a genotype, a phenotype, or any state associated with an adverse effect. In some embodiments, treating a disorder can comprise preventing, slowing progression of, reversing, or alleviating symptoms of the disorder. A method of treating a disorder can comprise delivering an engineered polynucleotide encoding an engineered guide RNA to a cell of a subject in need thereof and expressing the engineered guide RNA in the cell. In some embodiments, an engineered guide RNA of the present disclosure can be used to treat a genetic disorder (e.g., FSHD, DM1, CMT1A, or ALS). In some embodiments, an engineered guide RNA disclosed herein can be used to treat FSHD. In some cases, FSHD can comprise FSHD I or FSHD II. In some embodiments, an engineered guide RNA disclosed herein can be used to treat FSHD I. In some embodiments, an engineered guide RNA disclosed herein can be used to treat FSHD II. In some embodiments, an engineered guide RNA of the present disclosure can be used to treat a condition associated with one or more mutations. For example, disclosed herein are methods of treating FSHD with engineered guide RNAs targeting DUX4. Also disclosed herein are methods of treating DM1 with engineered guide RNAs targeting DMPK. Also disclosed herein are methods of treating CMT1A with engineered guide RNAs targeting PMP22. Also disclosed herein are methods of treating ALS with engineered guide RNAs targeting SOD1.

In some embodiments, treatment of FSHD comprises treatment of the symptoms associated with FSHD. A symptom of FSHD can comprise a weakness or atrophy of muscle, such as a muscle of the face, an arm muscle, a neck muscle, a shoulder muscle, a thigh muscle, a hip muscle, an abdominal muscle, a back muscle, a foot muscle, a hand muscle, or any combination thereof. In some cases, a symptom of FSHD can comprise a vision loss, a respiratory insufficiency, a dysphagia, a lordosis, a scoliosis, a hearing loss, a pain, an inflammation (e.g., inflammation of muscles), shoulder weakness, unequal (nonsymmetrical weakness) of the body, or any combination thereof.

Pharmaceutical Compositions

The compositions described herein (e.g., compositions comprising an engineered guide RNA or an engineered polynucleotide encoding an engineered guide RNA) can be formulated with a pharmaceutically acceptable carrier for administration to a subject (e.g., a human or a non-human animal). The compositions described herein (e.g., compositions comprising an engineered guide RNA or an engineered polynucleotide encoding an engineered guide RNA) can be formulated with a pharmaceutically acceptable: excipient, carrier, diluent or any combination thereof for administration to a subject (e.g., a human or a non-human animal). A pharmaceutically acceptable carrier and/or diluent can include, but is not limited to, phosphate buffered saline solution, water, emulsions (e.g., an oil/water emulsion or a water/oil emulsions), glycerol, liquid polyethylene glycols, aprotic solvents such (e.g., dimethylsulfoxide, N-methylpyrrolidone, or mixtures thereof), and various types of wetting agents, solubilizing agents, anti-oxidants, bulking agents, protein carriers such as albumins, any and all solvents, dispersion media, coatings, sodium lauryl sulfate, isotonic and absorption delaying agents, disintegrants (e.g., potato starch or sodium starch glycolate), and the like. The compositions also can include stabilizers and preservatives. Additional examples of carriers, stabilizers, and adjuvants consistent with the compositions of the present disclosure can be found in, for example, Remington's Pharmaceutical Sciences, 21st Ed., Mack Publ. Co., Easton, Pa. (2005), incorporated herein by reference in its entirety.

Delivery

An engineered guide RNA of the present disclosure or an engineered polynucleotide of the present disclosure (e.g., an engineered polynucleotide encoding an engineered guide RNA) can be delivered via a delivery vehicle. In some embodiments, the delivery vehicle is a vector. A vector can facilitate delivery of the engineered guide RNA or the engineered polynucleotide into a cell to genetically modify the cell. Target tissues and cells include but are not limited to satellite cells, myoblasts, myocytes, and myotubes of the face, shoulders, and upper limbs. In some examples, the vector comprises DNA, such as double stranded or single stranded DNA. In some examples, the delivery vector can be a eukaryotic vector, a prokaryotic vector (e.g., a bacterial vector or plasmid), a viral vector, or any combination thereof. In some cases, a delivery vehicle can comprise a non-viral delivery vehicle. In some embodiments, the vector is an expression cassette. In some embodiments, a viral vector comprises a viral capsid, an inverted terminal repeat sequence, and the engineered polynucleotide can be used to deliver the engineered guide RNA to a cell.

In some cases, the engineered guide RNA of the present disclosure can be an in vitro transcribed (IVT) RNA. In some cases, an engineered guide RNA can be delivered as a formulation comprising the engineered guide RNA. In some cases, the engineered guide RNA may not be comprised in a vector. In some examples, the engineered guide RNA (e.g., as an oligonucleotide) can be formulated for delivery through direct injection. In some examples, the engineered guide RNA, as an oligo nucleotide can be formulated for delivery through intravenous administration or oral administration.

In some embodiments, the viral vector can be a retroviral vector, an adenoviral vector, an adeno-associated viral (AAV) vector, an alphavirus vector, a lentivirus vector (e.g., human or porcine), a Herpes virus vector, an Epstein-Barr virus vector, an SV40 virus vectors, a pox virus vector, or a combination thereof. In some embodiments, the viral vector can be a recombinant vector, a hybrid vector, a chimeric vector, a self-complementary vector, a single-stranded vector, or any combination thereof.

In some embodiments, the viral vector can be an adeno-associated virus (AAV). In some embodiments, the AAV can be any AAV known in the art. In some embodiments, the AAV can comprise an AAV5 serotype, an AAV6 serotype, an AAV8 serotype, or an AAV9 serotype. In some embodiments, the viral vector can be of a specific serotype. In some embodiments, the viral vector can be an AAV1 serotype, an AAV2 serotype, an AAV3 serotype, an AAV4 serotype, an AAV5 serotype, an AAV6 serotype, an AAV7 serotype, an AAV8 serotype, an AAV9 serotype, an AAV10 serotype, an AAV 11 serotype, an AAV12 serotype, an AAV13 serotype, an AAV14 serotype, an AAV15 serotype, an AAV16 serotype, an AAV.rh8 serotype, an AAV.rh10 serotype, an AAV.rh20 serotype, an AAV.rh39 serotype, an AAV.Rh74 serotype, an AAV.RHM4-1 serotype, an AAV.hu37 serotype, an AAV.Anc80 serotype, an AAV.Anc80L65 serotype, an AAV.7m8 serotype, an AAV.PHP.B serotype, an AAV2.5 serotype, an AAV2tYF serotype, an AAV3B serotype, an AAV.LK03 serotype, an AAV.HSC1 serotype, an AAV.HSC2 serotype, an AAV.HSC3 serotype, an AAV.HSC4 serotype, an AAV.HSC5 serotype, an AAV.HSC6 serotype, an AAV.HSC7 serotype, an AAV.HSC8 serotype, an AAV.HSC9 serotype, an AAV.HSC10 serotype, an AAV.HSC11 serotype, an AAV.HSC12 serotype, an AAV.HSC13 serotype, an AAV.HSC14 serotype, an AAV.HSC15 serotype, an AAV.HSC16 serotype, and an AAVhu68 serotype, a derivative of any of these serotypes, a chimera of any of these serotypes, a variant of any of these serotypes or any combination thereof.

In some embodiments, the AAV vector can be a recombinant vector, a hybrid AAV vector, a chimeric AAV vector, a self-complementary AAV (scAAV) vector, a single-stranded AAV, or any combination thereof.

In some embodiments, the AAV vector can be a recombinant AAV (rAAV) vector. Methods of producing recombinant AAV vectors can be known in the art and generally involve, in some cases, introducing into a producer cell line: (1) DNA necessary for AAV replication and synthesis of an AAV capsid, (b) one or more helper constructs comprising the viral functions missing from the AAV vector, (c) a helper virus, and (d) the plasmid construct containing the genome of the AAV vector, e.g., ITRs, promoter and engineered guide RNA sequences, etc. In some examples, the viral vectors described herein can be engineered through synthetic or other suitable means by references to published sequences, such as those that can be available in the literature. For example, the genomic and protein sequences of various serotypes of AAV, as well as the sequences of the native terminal repeats (TRs), Rep proteins, and capsid subunits can be known in the art and can be found in the literature or in public databases such as GenBank or Protein Data Bank (PDB).

In some examples, methods of producing delivery vectors herein comprising packaging an engineered polynucleotide of the present disclosure (e.g., an engineered polynucleotide encoding an engineered guide RNA) in an AAV vector. In some examples, methods of producing the delivery vectors described herein comprise, (a) introducing into a cell: (i) a polynucleotide comprising a promoter and an engineered guide RNA payload disclosed herein; and (ii) a viral genome comprising a Replication (Rep) gene and Capsid (Cap) gene that encodes a wild-type AAV capsid protein or modified version thereof, (b) expressing in the cell the wild-type AAV capsid protein or modified version thereof; (c) assembling an AAV particle; and (d) packaging the payload disclosed herein in the AAV particle, thereby generating an AAV delivery vector. In some examples, the recombinant vectors comprise one or more inverted terminal repeats and the inverted terminal repeats comprise a 5′ inverted terminal repeat, a 3′ inverted terminal repeat, and a mutated inverted terminal repeat. In some examples, the mutated terminal repeat lacks a terminal resolution site, thereby enabling formation of a self-complementary AAV.

In some examples, a hybrid AAV vector can be produced by transcapsidation, e.g., packaging an inverted terminal repeat (ITR) from a first serotype into a capsid of a second serotype, wherein the first and second serotypes may not be the same. In some examples, the Rep gene and ITR from a first AAV serotype (e.g., AAV2) can be used in a capsid from a second AAV serotype (e.g., AAV5 or AAV9), wherein the first and second AAV serotypes may not be the same. As a non-limiting example, a hybrid AAV serotype comprising the AAV2 ITRs and AAV9 capsid protein can be indicated AAV2/9. In some examples, the hybrid AAV delivery vector comprises an AAV2/1, AAV2/2, AAV 2/4, AAV2/5, AAV2/8, or AAV2/9 vector.

In some examples, the AAV vector can be a chimeric AAV vector. In some examples, the chimeric AAV vector comprises an exogenous amino acid or an amino acid substitution, or capsid proteins from two or more serotypes. In some examples, a chimeric AAV vector can be genetically engineered to increase transduction efficiency, selectivity, or a combination thereof.

In some examples, the AAV vector comprises a self-complementary AAV genome. Self-complementary AAV genomes can be generally known in the art and contain both DNA strands which can anneal together to form double-stranded DNA.

In some examples, the delivery vector can be a retroviral vector. In some examples, the retroviral vector can be a Moloney Murine Leukemia Virus vector, a spleen necrosis virus vector, or a vector derived from the Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, human immunodeficiency virus, myeloproliferative sarcoma virus, or mammary tumor virus, or a combination thereof. In some examples, the retroviral vector can be transfected such that the majority of sequences coding for the structural genes of the virus (e.g., gag, pol, and env) can be deleted and replaced by the gene(s) of interest.

In some examples, the delivery vehicle can be a non-viral vector. In some cases, the delivery vehicle can be a DNA encoding the engineered guide RNA. In some examples, the delivery vehicle can be a plasmid. In some embodiments, the plasmid comprises DNA. In some examples, the plasmid comprises circular double-stranded DNA. In some examples, the plasmid can be linear. In some examples, the plasmid comprises one or more genes of interest and one or more regulatory elements. In some examples, the plasmid comprises a bacterial backbone containing an origin of replication and an antibiotic resistance gene or other selectable marker for plasmid amplification in bacteria. In some examples, the plasmid can be a minicircle plasmid. In some examples, the plasmid contains one or more genes that provide a selective marker to induce a target cell to retain the plasmid. In some examples, the plasmid can be formulated for delivery through injection by a needle carrying syringe. In some examples, the plasmid can be formulated for delivery via electroporation. In some examples, the plasmids can be engineered through synthetic or other suitable means known in the art. For example, in some cases, the genetic elements can be assembled by restriction digest of the desired genetic sequence from a donor plasmid or organism to produce ends of the DNA which can then be readily ligated to another genetic sequence.

In some embodiments, the vector containing the engineered guide RNA or the engineered polynucleotide is a non-viral vector system. In some embodiments, the non-viral vector system comprises cationic lipids, or polymers. For example, the non-viral vector system can be a liposome or polymeric nanoparticle. In some cases, a non-viral vector system can be a lipid nanoparticle (LNP) or a polymer nanoparticle. In some embodiments, the engineered polynucleotide or a non-viral vector comprising the engineered guide RNA or the engineered polynucleotide is delivered to a cell by hydrodynamic injection or ultrasound.

Administration

Administration can refer to methods that can be used to enable the delivery of a composition described herein (e.g. comprising an engineered guide RNA or an engineered polynucleotide encoding the same) to the desired site of biological action. For example, an engineered guide RNA can be comprised in a DNA construct, a viral vector, or both and be administered by intravenous administration. Administration disclosed herein to an area in need of treatment or therapy can be achieved by, for example, and not by way of limitation, oral administration, topical administration, intravenous administration, inhalation administration, or any combination thereof. In some cases, administration disclosed herein can be a systemic administration. In some instances, administration can be systemic administration by an injection (e.g., intravenous administration or any administration by an injection) or oral delivery. In some embodiments, delivery can include inhalation, otic, buccal, conjunctival, dental, endocervical, endosinusial, endotracheal, enteral, epidural, extra-amniotic, extracorporeal, hemodialysis, infiltration, interstitial, intraabdominal, intraamniotic, intraarterial, intraarticular, intrabiliary, intrabronchial, intrabursal, intracardiac, intracartilaginous, intracaudal, intracavernous, intracavitary, intracerebroventricular, intracisternal, intracorneal, intracoronal, intracoronary, intracorpous cavernaosum, intradermal, intradiscal, intraductal, intraduodenal, intradural, intraepidermal, intraesophageal, intragastric, intragingival, intrahippocampal, intraileal, intralesional, intraluminal, intralymphatic, intramedullary, intrameningeal, intramuscular, intraocular, intraovarian, intrapericardial, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrasinal, intraspinal, intrasynovial, intratendinous, intratesticular, intrathoracic, intratubular, intratumor, intratympanic, intrauterine, intravascular, intravenous, intravenous bolus, intravenous drip, intravesical, intravitreal, iontophoresis, irrigation, laryngeal, nasal, nasogastric, ophthalmic, oral, oropharyngeal, parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, retrobulbar, subarachnoid, subconjunctival, subcutaneous, sublingual, submucosal, topical, transdermal, transmucosal, transplacental, transtracheal, transtympanic, ureteral, urethral, vaginal, infraorbital, intraparenchymal, intrathecal, intraventricular, stereotactic, or any combination thereof. Delivery can include parenteral administration (including intravenous, subcutaneous, intrathecal, intraperitoneal, intramuscular, intravascular or infusion), oral administration, inhalation administration, intraduodenal administration, rectal administration, or a combination thereof. Delivery can include direct application to the affected tissue or region of the body. In some cases, topical administration can comprise administering a lotion, a solution, an emulsion, a cream, a balm, an oil, a paste, a stick, an aerosol, a foam, a jelly, a foam, a mask, a pad, a powder, a solid, a tincture, a butter, a patch, a gel, a spray, a drip, a liquid formulation, an ointment to an external surface of a surface, such as a skin. Delivery can include a parenchymal injection, an intra-thecal injection, an intra-ventricular injection, or an intra-cisternal injection. A composition provided herein can be administered by any method. A method of administration can be by intra-arterial injection, intracisternal injection, intramuscular injection, intraparenchymal injection, intraperitoneal injection, intraspinal injection, intrathecal injection, intravenous injection, intraventricular injection, stereotactic injection, subcutaneous injection, epidural, or any combination thereof. Delivery can include parenteral administration (including intravenous, subcutaneous, intrathecal, intraperitoneal, intramuscular, intravascular or infusion administration). In some embodiments, delivery can comprise a nanoparticle, a liposome, an exosome, an extracellular vesicle, an implant, or a combination thereof. In some cases, delivery can be from a device. In some instances, delivery can be administered by a pump, an infusion pump, or a combination thereof. In some embodiments, delivery can be by an enema, an eye drop, a nasal spray, or any combination thereof. In some instances, a subject can administer the composition in the absence of supervision. In some instances, a subject can administer the composition under the supervision of a medical professional (e.g., a physician, nurse, physician's assistant, orderly, hospice worker, etc.). In some embodiments, a medical professional can administer the composition.

In some cases, administering can be oral ingestion. In some cases, delivery can be a capsule or a tablet. Oral ingestion delivery can comprise a tea, an elixir, a food, a drink, a beverage, a syrup, a liquid, a gel, a capsule, a tablet, an oil, a tincture, or any combination thereof. In some embodiments, a food can be a medical food. In some instances, a capsule can comprise hydroxymethylcellulose. In some embodiments, a capsule can comprise a gelatin, hydroxypropylmethyl cellulose, pullulan, or any combination thereof. In some cases, capsules can comprise a coating, for example, an enteric coating. In some embodiments, a capsule can comprise a vegetarian product or a vegan product such as a hypromellose capsule. In some embodiments, delivery can comprise inhalation by an inhaler, a diffuser, a nebulizer, a vaporizer, or a combination thereof.

In some embodiments, an engineered guide RNA disclosed herein or a polynucleotide encoding the engineered guide RNA can be administered with a second therapeutic. In some cases, the second therapeutic can be administered in an amount sufficient to treat a disease or condition. In some cases, administration of the second therapeutic can be concurrent administration or consecutive administration to administration of the engineered guide RNA disclosed herein or the polynucleotide encoding the engineered guide RNA. In some cases, the second therapeutic can comprise losmapimod or a salt thereof. In some cases, losmapimod or a salt thereof can be administered in an amount of about: 0.0001 gram to about 100 grams or about 1 mg to about 100 mg.

In some embodiments, disclosed herein can be a method, comprising administering a composition disclosed herein to a subject (e.g., a human) in need thereof. In some instances, the method can treat or prevent a disease in the subject.

Definitions

Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art.

Throughout this application, various embodiments are presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

As used herein, the term “about” a number can refer to that number plus or minus 10% of that number.

As disclosed herein, a “bulge” refers to the structure substantially formed only upon formation of the guide-target RNA scaffold, where contiguous nucleotides in either the engineered guide RNA or the target RNA are not complementary to their positional counterparts on the opposite strand. A bulge can independently have from 0 to 4 contiguous nucleotides on the guide RNA side of the guide-target RNA scaffold and 1 to 4 contiguous nucleotides on the target RNA side of the guide-target RNA scaffold or a bulge can independently have from 0 to 4 nucleotides on the target RNA side of the guide-target RNA scaffold and 1 to 4 contiguous nucleotides on the guide RNA side of the guide-target RNA scaffold. However, a bulge, as used herein, does not refer to a structure where a single participating nucleotide of the engineered guide RNA and a single participating nucleotide of the target RNA do not base pair—a single participating nucleotide of the engineered guide RNA and a single participating nucleotide of the target RNA that do not base pair is referred to herein as a “mismatch.” Further, where the number of participating nucleotides on either the guide RNA side or the target RNA side exceeds 4, the resulting structure is no longer considered a bulge, but rather, is considered an “internal loop.” A “symmetrical bulge” refers to a bulge where the same number of nucleotides is present on each side of the bulge. An “asymmetrical bulge” refers to a bulge where a different number of nucleotides are present on each side of the bulge.

The term “complementary” or “complementarity” refers to the ability of a nucleic acid to form one or more bonds with a corresponding nucleic acid sequence by, for example, hydrogen bonding (e.g., traditional Watson-Crick), covalent bonding, or other similar methods. In Watson-Crick base pairing, a double hydrogen bond forms between nucleobases T and A, whereas a triple hydrogen bond forms between nucleobases C and G. For example, the sequence A-G-T can be complementary to the sequence T-C-A. A percent complementarity indicates the percentage of residues in a nucleic acid molecule which can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 being 50%, 60%, 70%, 80%, 90%, and 100% complementary, respectively). “Perfectly complementary” can mean that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic acid sequence. “Substantially complementary” as used herein can refer to a degree of complementarity that can be at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%. 97%, 98%, 99%, or 100% over a region of 10, 15, 20, 25, 30, 35, 40, 45, 50, or more nucleotides, or can refer to two nucleic acids that hybridize under stringent conditions (i.e., stringent hybridization conditions). Nucleic acids can include nonspecific sequences. As used herein, the term “nonspecific sequence” or “not specific” can refer to a nucleic acid sequence that contains a series of residues that may not be designed to be complementary to or can be only partially complementary to any other nucleic acid sequence.

The terms “determining,” “measuring,” “evaluating,” “assessing,” “assaying,” and “analyzing” can be used interchangeably herein to refer to forms of measurement. The terms include determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. “Detecting the presence of” can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.

The term “encode,” as used herein, refers to an ability of a polynucleotide to provide information or instructions sequence sufficient to produce a corresponding gene expression product. In a non-limiting example, mRNA can encode a polypeptide during translation, whereas DNA can encode an mRNA molecule during transcription.

An “engineered latent guide RNA” refers to an engineered guide RNA that comprises a portion of sequence that, upon hybridization or only upon hybridization to a target RNA, substantially forms at least a portion of a structural feature, other than a single A/C mismatch feature at the target adenosine to be edited.

As used herein, the term “facilitates RNA editing” by an engineered guide RNA refers to the ability of the engineered guide RNA when associated with an RNA editing entity and a target RNA to provide a targeted edit of the target RNA by the RNA edited entity. In some instances, the engineered guide RNA can directly recruit or position/orient the RNA editing entity to the proper location for editing of the target RNA. In other instances, the engineered guide RNA when hybridized to the target RNA forms a guide-target RNA scaffold with one or more structural features as described herein, where the guide-target RNA scaffold with structural features recruits or positions/orients the RNA editing entity to the proper location for editing of the target RNA.

A “guide-target RNA scaffold,” as disclosed herein, is the resulting double stranded RNA formed upon hybridization of a guide RNA, with latent structure, to a target RNA. A guide-target RNA scaffold has one or more structural features formed within the double stranded RNA duplex upon hybridization. For example, the guide-target RNA scaffold can have one or more structural features selected from a bulge, mismatch, internal loop, hairpin, or wobble base pair.

As disclosed herein, a “hairpin” includes an RNA duplex wherein a portion of a single RNA strand has folded in upon itself to form the RNA duplex. The portion of the single RNA strand folds upon itself due to having nucleotide sequences that base pair to each other, where the nucleotide sequences are separated by an intervening sequence that does not base pair with itself, thus forming a base-paired portion and non-base paired, intervening loop portion.

As used herein, the term percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, can refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., BLASTP and BLASTN or other algorithms available to persons of skill) or by visual inspection. Depending on the application, the percent “identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared.

For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.

For purposes herein, percent identity and sequence similarity can be performed using the BLAST algorithm, which is described in Altschul et al. (J. Mol. Biol. 215:403-410 (1990)). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information.

As disclosed herein, an “internal loop” refers to the structure substantially formed only upon formation of the guide-target RNA scaffold, where nucleotides in either the engineered guide RNA or the target RNA are not complementary to their positional counterparts on the opposite strand and where one side of the internal loop, either on the target RNA side or the engineered guide RNA side of the guide-target RNA scaffold, has 5 nucleotides or more. Where the number of participating nucleotides on both the guide RNA side and the target RNA side drops below 5, the resulting structure is no longer considered an internal loop, but rather, is considered a “bulge” or a “mismatch,” depending on the size of the structural feature. A “symmetrical internal loop” is formed when the same number of nucleotides is present on each side of the internal loop. An “asymmetrical internal loop” is formed when a different number of nucleotides is present on each side of the internal loop.

“Latent structure” refers to a structural feature that substantially forms only upon hybridization of a guide RNA to a target RNA. For example, the sequence of a guide RNA provides one or more structural features, but these structural features substantially form only upon hybridization to the target RNA, and thus the one or more latent structural features manifest as structural features upon hybridization to the target RNA. Upon hybridization of the guide RNA to the target RNA, the structural feature is formed and the latent structure provided in the guide RNA is, thus, unmasked.

“Messenger RNA” or “mRNA” are RNA molecules comprising a sequence that encodes a polypeptide or protein. In general, RNA can be transcribed from DNA. In some cases, precursor mRNA containing non-protein coding regions in the sequence can be transcribed from DNA and then processed to remove all or a portion of the non-coding regions (introns) to produce mature mRNA. As used herein, the term “pre-mRNA” can refer to the RNA molecule transcribed from DNA before undergoing processing to remove the non-protein coding regions.

As disclosed herein, a “mismatch” refers to a single nucleotide in a guide RNA that is unpaired to an opposing single nucleotide in a target RNA within the guide-target RNA scaffold. A mismatch can comprise any two single nucleotides that do not base pair. Where the number of participating nucleotides on the guide RNA side and the target RNA side exceeds 1, the resulting structure is no longer considered a mismatch, but rather, is considered a “bulge” or an “internal loop,” depending on the size of the structural feature.

As used herein, the term “polynucleotide” can refer to a single or double-stranded polymer of deoxyribonucleotide (DNA) or ribonucleotide (RNA) bases read from the 5′ to the 3′ end. The term “RNA” is inclusive of dsRNA (double stranded RNA), snRNA (small nuclear RNA), lncRNA (long non-coding RNA), mRNA (messenger RNA), miRNA (microRNA) RNAi (inhibitory RNA), siRNA (small interfering RNA), shRNA (short hairpin RNA), tRNA (transfer RNA), rRNA (ribosomal RNA), snoRNA (small nucleolar RNA), and cRNA (complementary RNA). The term DNA is inclusive of cDNA, genomic DNA, and DNA-RNA hybrids.

The term “protein”, “peptide” and “polypeptide” can be used interchangeably and in their broadest sense can refer to a compound of two or more subunit amino acids, amino acid analogs or peptidomimetics. The subunits can be linked by peptide bonds. In another embodiment, the subunit can be linked by other bonds, e.g., ester, ether, etc. A protein or peptide can contain at least two amino acids and no limitation can be placed on the maximum number of amino acids which can comprise a protein's or peptide's sequence. As used herein the term “amino acid” can refer to either natural amino acids, unnatural amino acids, or synthetic amino acids, including glycine and both the D and L optical isomers, amino acid analogs and peptidomimetics. As used herein, the term “fusion protein” can refer to a protein comprised of domains from more than one naturally occurring or recombinantly produced protein, where generally each domain serves a different function. In this regard, the term “linker” can refer to a protein fragment that can be used to link these domains together —optionally to preserve the conformation of the fused protein domains, prevent unfavorable interactions between the fused protein domains which can compromise their respective functions, or both.

The term “structured motif” refers to a combination of two or more structural features in a guide-target RNA scaffold.

The terms “subject,” “individual,” or “patient” can be used interchangeably herein. A “subject” refers to a biological entity containing expressed genetic materials. The biological entity can be a plant, animal, or microorganism, including, for example, bacteria, viruses, fungi, and protozoa. The subject can be tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro. The subject can be a mammal. The mammal can be a human. The subject can be diagnosed or suspected of being at high risk for a disease. In some cases, the subject is not necessarily diagnosed or suspected of being at high risk for the disease

The term “in vivo” refers to an event that takes place in a subject's body.

The term “ex vivo” refers to an event that takes place outside of a subject's body. An ex vivo assay may not be performed on a subject. Rather, it can be performed upon a sample separate from a subject. An example of an ex vivo assay performed on a sample can be an “in vitro” assay.

The term “in vitro” refers to an event that takes places contained in a container for holding laboratory reagent such that it can be separated from the biological source from which the material can be obtained. In vitro assays can encompass cell-based assays in which living or dead cells can be employed. In vitro assays can also encompass a cell-free assay in which no intact cells can be employed.

The term “wobble base pair” refers to two bases that weakly pair. For example, a wobble base pair can refer to a G paired with a U.

The term “substantially forms” as described herein, when referring to a particular secondary structure, refers to formation of at least 80% of the structure under physiological conditions (e.g. physiological pH, physiological temperature, physiological salt concentration, etc.).

As used herein, the terms “treatment” or “treating” can be used in reference to a pharmaceutical or other intervention regimen for obtaining beneficial or desired results in the recipient. Beneficial or desired results include but are not limited to a therapeutic benefit and/or a prophylactic benefit. A therapeutic benefit can refer to eradication or amelioration of one or more symptoms of an underlying disorder being treated. Also, a therapeutic benefit can be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement can be observed in the subject, notwithstanding that the subject can still be afflicted with the underlying disorder. A prophylactic effect includes delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of one or more symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof. For prophylactic benefit, a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease can undergo treatment, even though a diagnosis of this disease may not have been made.

NUMBERED EMBODIMENTS

A number of compositions, and methods are disclosed herein. Specific exemplary embodiments of these compositions and methods are disclosed below. The following embodiments recite non-limiting permutations of combinations of features disclosed herein. Other permutations of combinations of features are also contemplated. In particular, each of these numbered embodiments is contemplated as depending from or relating to every previous or subsequent numbered embodiment, independent of their order as listed.

Embodiments Section 1

Embodiment 1. A composition comprising an engineered guide RNA, wherein:

- a) the engineered guide RNA, upon hybridization to a sequence of a target RNA, forms a guide-target RNA scaffold with the sequence of the target RNA;
- b) formation of the guide-target RNA scaffold substantially forms one or more structural features selected from the group consisting of: a bulge, an internal loop, and a hairpin; and
- c) the sequence of the target RNA is a sequence of the target RNA is selected from the group consisting of: a translation initiation site, a polyA signal sequence, and any combination thereof.

Embodiment 2. The composition of embodiment 1, wherein the sequence of the target RNA comprises the translation initiation site.

Embodiment 3. The composition of embodiment 1, wherein the sequence of the target RNA comprises the polyA signal site.

Embodiment 4. The composition of any one of embodiments 1-2, wherein upon hybridization of the engineered guide RNA to the sequence of the target RNA, the engineered guide RNA facilitates RNA editing of one or more adenosines in the sequence of the target RNA by an RNA editing entity.

Embodiment 5. The composition of any one of embodiments 1-4, wherein the target RNA is selected from the group consisting of DUX4, DMPK, PMP22, and SOD1.

Embodiment 6. The composition of any one of embodiments 1-4, wherein the target RNA comprises DUX4-FL.

Embodiment 7. The composition of embodiment 6, wherein the sequence of the target RNA comprises the polyA signal sequence, wherein the polyA signal sequence is in DUX4-FL.

Embodiment 8. The composition of embodiment 7, wherein the polyA signal sequence comprises ATTAAA.

Embodiment 9. The composition of embodiment 8, wherein one or more adenosines in the polyA signal sequence of ATTAAA is edited by the RNA editing entity.

Embodiment 10. The composition of any one of embodiments 1-9, wherein the one or more structural features comprises the bulge, wherein the bulge is a symmetric bulge.

Embodiment 11. The composition of any one of embodiments 1-9, wherein the one or more structural features comprises the bulge, wherein the bulge is an asymmetric bulge.

Embodiment 12. The composition of any one of embodiments 1-11, wherein the one or more structural features comprises the internal loop, wherein the internal loop is a symmetric internal loop.

Embodiment 13. The composition of any one of embodiments 1-11, wherein the one or more structural features comprises the internal loop, wherein the internal loop is an asymmetric internal loop.

Embodiment 14. The composition of any one of embodiments 1-13, wherein the guide-target RNA scaffold comprises a Wobble base pair.

Embodiment 15. The composition of any one of embodiments 1-14, wherein the one or more structural features comprises the hairpin, wherein the hairpin is a recruitment hairpin or a non-recruitment hairpin.

Embodiment 16. The composition of embodiment 4, wherein the RNA editing entity comprises ADAR1, ADAR2, ADAR3, or any combination thereof.

Embodiment 17. The composition of any one of embodiments 1-16, wherein the engineered guide RNA is encoded by an engineered polynucleotide.

Embodiment 18. The composition of embodiment 17, wherein the engineered polynucleotide is comprised in or on a vector.

Embodiment 19. The composition of embodiment 18, wherein the vector is a viral vector, and wherein the engineered polynucleotide is encapsidated in the viral vector.

Embodiment 20. The composition of embodiment 19, wherein the viral vector is an adeno-associated viral (AAV) vector or a derivative thereof.

Embodiment 21. The composition of embodiment 20, wherein the AAV vector is AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV 11, or a derivative, a chimera, or a variant thereof.

Embodiment 22. The composition of any one of embodiments 20-21, wherein the AAV vector is a recombinant AAV (rAAV) vector, a hybrid AAV vector, a chimeric AAV vector, a self-complementary AAV (scAAV) vector, or any combination thereof

Embodiment 23. The composition of any one of embodiments 1-22, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 2-SEQ ID NO: 1589.

Embodiment 24. The composition of any one of embodiments 1-22, wherein the engineered guide RNA has a sequence of any one of SEQ ID NO: 2-SEQ ID NO: 1589.

Embodiment 25. A pharmaceutical composition comprising:

- (a) the composition of any one of embodiments 1-24; and
- (b) a pharmaceutically acceptable: excipient, carrier, or diluent.

Embodiment 26. A method of treating a disease or a condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of any one of embodiments 1-24 or the pharmaceutical composition of embodiment 25.

Embodiment 27. The method of embodiment 26, wherein the disease or condition comprises facioscapulohumeral muscular dystrophy and the target RNA is DUX4.

Embodiment 28. The method of embodiment 26, wherein the disease or condition comprises myotonic dystrophy and the target RNA is DMPK.

Embodiment 29. The method of embodiment 26, wherein the disease or condition comprises Charcot-Marie-Tooth Syndrome and the target RNA is PMP22.

Embodiment 30. The method of embodiment 26, wherein the disease or condition comprises amyotrophic lateral sclerosis and the target RNA is SOD1.

Embodiments section 2:

1. A composition comprising an engineered guide RNA or an engineered polynucleotide encoding the engineered guide RNA, wherein: a) the engineered guide RNA, upon hybridization to a sequence of a DUX4 target RNA, forms a guide-target RNA scaffold with the sequence of the DUX4 target RNA; b) formation of the guide-target RNA scaffold substantially forms one or more structural features selected from the group consisting of: a bulge, an internal loop, a hairpin, and a mismatch formed by a base in the engineered guide RNA to a G, a C, or a U in the DUX4 target RNA; and c) the structural feature is not present within the engineered guide RNA prior to the hybridization of the engineered guide RNA to the DUX4 target RNA; and d) upon hybridization of the engineered guide RNA to the sequence of the DUX4 target RNA, the engineered guide RNA facilitates RNA editing of one or more target adenosines in the sequence of the DUX4 target RNA by an RNA editing entity. 2. The composition of embodiment 1, wherein the sequence of the DUX4 target RNA comprises a translation initiation site, a polyA signal sequence, a splice site, or any combination thereof. 3. The composition of embodiment 2, wherein the sequence of the DUX4 target RNA comprises the translation initiation site. 4. The composition of embodiment 2, wherein the sequence of the DUX4 target RNA comprises the polyA signal sequence. 5. The composition of embodiment 1, wherein the one or more features further comprises a mismatch formed by a base in the engineered guide RNA to an A in the DUX4 target RNA. 6. The composition of embodiment 1, wherein the DUX4 is DUX4-FL. 7. The composition of embodiment 6, wherein the sequence of the DUX4 target RNA comprises the polyA signal sequence, wherein the polyA signal sequence is in DUX4-FL. 8. The composition of embodiment 7, wherein the polyA signal sequence comprises ATTAAA. 9. The composition of embodiment 8, wherein any A of the ATTAAA polyA signal sequence is the target adenosine. 10. The composition of any one of embodiments 6-9, wherein position 0 of ATTAAA is the target adenosine, wherein position 0 is the first A of ATTAAA at the 5′ end. 11. The composition of embodiment 10, wherein the one or more structural features comprises: a first 6/6 symmetric internal loop at a position selected from the group consisting of: −3, −4, −5, −6, −7, −8, −9, −10, and −11, relative to position 0 of ATTAAA. 12. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −3 relative to position 0. 13. The composition of embodiment 12, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 24 relative to position 0, and a combination thereof 14. The composition of embodiment 13, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1236. 15. The composition of embodiment 14, wherein the engineered guide RNA comprises SEQ ID NO: 1236. 16. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −4 relative to position 0. 17. The composition of embodiment 16, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 18. The composition of embodiment 17, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1211. 19. The composition of embodiment 18, wherein the engineered guide RNA comprises SEQ ID NO: 1211. 20. The composition of embodiment 16, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 23 relative to position 0, and a combination thereof. 21. The composition of embodiment 20, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1117. 22. The composition of embodiment 21, wherein the engineered guide RNA comprises SEQ ID NO: 1117. 23. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −5 relative to position 0. 24. The composition of embodiment 23, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 24 relative to position 0, and a combination thereof. 25. The composition of embodiment 24, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1008. 26. The composition of embodiment 25, wherein the engineered guide RNA comprises SEQ ID NO: 1008. 27. The composition of embodiment 23, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 33 relative to position 0. 28. The composition of embodiment 27, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. 29. The composition of embodiment 28, wherein the engineered guide RNA comprises SEQ ID NO: 1054. 30. The composition of embodiment 23, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof 31. The composition of embodiment 30, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1103. 32. The composition of embodiment 31, wherein the engineered guide RNA comprises SEQ ID NO: 1103. 33. The composition of embodiment 23, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 43 relative to position 0, and a combination thereof. 34. The composition of embodiment 33, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1098. 35. The composition of embodiment 34, wherein the engineered guide RNA comprises SEQ ID NO: 1098. 36. The composition of embodiment 23, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof. 37. The composition of embodiment 36, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1104. 38. The composition of embodiment 37, wherein the engineered guide RNA comprises SEQ ID NO: 1104. 39. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −6 relative to position 0. 40. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 41. The composition of embodiment 40, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 977. 42. The composition of embodiment 41, wherein the engineered guide RNA comprises SEQ ID NO: 977. 43. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 27 relative to position 0, and a combination thereof. 44. The composition of embodiment 43, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 906. 45. The composition of embodiment 44, wherein the engineered guide RNA comprises SEQ ID NO: 906. 46. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. 47. The composition of embodiment 46, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 937. 48. The composition of embodiment 47, wherein the engineered guide RNA comprises SEQ ID NO: 937. 49. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof 50. The composition of embodiment 49, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 934. 51. The composition of embodiment 50, wherein the engineered guide RNA comprises SEQ ID NO: 934. 52. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 53 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof 53. The composition of embodiment 52, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1584. 54. The composition of embodiment 53, wherein the engineered guide RNA comprises SEQ ID NO: 1584. 55. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 internal loop at position 53 relative to position 0, a 5/5 internal loop at position 72 relative to position 0, and any combination thereof. 56. The composition of embodiment 55, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1585. 57. The composition of embodiment 56, wherein the engineered guide RNA comprises SEQ ID NO: 1585. 58. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 internal loop at position 51 relative to position 0, a 5/5 internal loop at position 68 relative to position 0, and any combination thereof. 59. The composition of embodiment 58, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1581. 60. The composition of embodiment 59, wherein the engineered guide RNA comprises SEQ ID NO: 1581. 61. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 51 relative to position 0, a 2/2 symmetric bulge at position 65 relative to position 0, and any combination thereof 62. The composition of embodiment 61, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1578. 63. The composition of embodiment 62, wherein the engineered guide RNA comprises SEQ ID NO: 1578. 64. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. 65. The composition of embodiment 64, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. 66. The composition of embodiment 65, wherein the engineered guide RNA comprises SEQ ID NO: 1575. 67. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 internal loop at position 47 relative to position 0, a 5/5 internal loop at position 60 relative to position 0, a 5/5 internal loop at position 73 relative to position 0, and any combination thereof. 68. The composition of embodiment 67, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. 69. The composition of embodiment 68, wherein the engineered guide RNA comprises SEQ ID NO: 1573. 70. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 internal loop at position 45 relative to position 0, a 5/5 internal loop at position 56 relative to position 0, a 5/5 internal loop at position 67 relative to position 0, and any combination thereof. 71. The composition of embodiment 70, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. 72. The composition of embodiment 71, wherein the engineered guide RNA comprises SEQ ID NO: 1569. 73. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. 74. The composition of embodiment 73, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. 75. The composition of embodiment 74, wherein the engineered guide RNA comprises SEQ ID NO: 1567. 76. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 47 relative to position 0, a 3/3 symmetric bulge at position 58 relative to position 0, a 3/3 symmetric bulge at position 69 relative to position 0, and any combination thereof. 77. The composition of embodiment 76, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1571. 78. The composition of embodiment 77, wherein the engineered guide RNA comprises SEQ ID NO: 1571. 79. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 49 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 80. The composition of embodiment 79, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1574. 81. The composition of embodiment 80, wherein the engineered guide RNA comprises SEQ ID NO: 1574. 82. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 47 relative to position 0, a 2/2 symmetric bulge at position 57 relative to position 0, a 2/2 symmetric bulge at position 67 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 83. The composition of embodiment 82, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1570. 84. The composition of embodiment 83, wherein the engineered guide RNA comprises SEQ ID NO: 1570. 85. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 45 relative to position 0, a 2/2 symmetric bulge at position 53 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 69 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 86. The composition of embodiment 85, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1566. 87. The composition of embodiment 86, wherein the engineered guide RNA comprises SEQ ID NO: 1566. 88. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 47 relative to position 0, a 4/4 symmetric bulge at position 59 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 89. The composition of embodiment 88, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1572. 90. The composition of embodiment 89, wherein the engineered guide RNA comprises SEQ ID NO: 1572. 91. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 55 relative to position 0, a 3/3 symmetric bulge at position 74 relative to position 0, and any combination thereof 92. The composition of embodiment 91, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1587. 93. The composition of embodiment 92, wherein the engineered guide RNA comprises SEQ ID NO: 1587. 94. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof 95. The composition of embodiment 94, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. 96. The composition of embodiment 95, wherein the engineered guide RNA comprises SEQ ID NO: 1588. 97. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 55 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof 98. The composition of embodiment 97, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1586. 99. The composition of embodiment 98, wherein the engineered guide RNA comprises SEQ ID NO: 1586. 100. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 51 relative to position 0, a 4/4 symmetric bulge at position 67 relative to position 0, and any combination thereof. 101. The composition of embodiment 100, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1580. 102. The composition of embodiment 101, wherein the engineered guide RNA comprises SEQ ID NO: 1580. 103. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof 104. The composition of embodiment 103, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 985. 105. The composition of embodiment 104, wherein the engineered guide RNA comprises SEQ ID NO: 985. 106. The composition of embodiment 39, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 107. The composition of embodiment 106, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 976. 108. The composition of embodiment 107, wherein the engineered guide RNA comprises SEQ ID NO: 976. 109. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −7 relative to position 0. 110. The composition of embodiment 109, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 25 relative to position 0, and a combination thereof. 111. The composition of embodiment 110, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 769. 112. The composition of embodiment 111, wherein the engineered guide RNA comprises SEQ ID NO: 769. 113. The composition of embodiment 109, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof 114. The composition of embodiment 113, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 851. 115. The composition of embodiment 114, wherein the engineered guide RNA comprises SEQ ID NO: 851. 116. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −8 relative to position 0. 117. The composition of embodiment 116, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof 118. The composition of embodiment 117, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 679. 119. The composition of embodiment 118, wherein the engineered guide RNA comprises SEQ ID NO: 679. 120. The composition of embodiment 116, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 121. The composition of embodiment 120, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 727. 122. The composition of embodiment 121, wherein the engineered guide RNA comprises SEQ ID NO: 727. 123. The composition of embodiment 116, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 24 relative to position 0, and a combination thereof. 124. The composition of embodiment 123, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 642. 125. The composition of embodiment 124, wherein the engineered guide RNA comprises SEQ ID NO: 642. 126. The composition of embodiment 116, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof. 127. The composition of embodiment 126, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 737. 128. The composition of embodiment 127, wherein the engineered guide RNA comprises SEQ ID NO: 737. 129. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −9 relative to position 0. 130. The composition of embodiment 129, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 22 relative to position 0, and a combination thereof 131. The composition of embodiment 130, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 512. 132. The composition of embodiment 131, wherein the engineered guide RNA comprises SEQ ID NO: 512. 133. The composition of embodiment 129, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. 134. The composition of embodiment 133, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 593. 135. The composition of embodiment 134, wherein the engineered guide RNA comprises SEQ ID NO: 593. 136. The composition of embodiment 129, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof. 137. The composition of embodiment 136, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 502. 138. The composition of embodiment 137, wherein the engineered guide RNA comprises SEQ ID NO: 502. 139. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −10 relative to position 0. 140. The composition of embodiment 139, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 43 relative to position 0, and a combination thereof. 141. The composition of embodiment 140, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 487. 142. The composition of embodiment 141, wherein the engineered guide RNA comprises SEQ ID NO: 487. 143. The composition of embodiment 139, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 27 relative to position 0, and a combination thereof 144. The composition of embodiment 143, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 408. 145. The composition of embodiment 144, wherein the engineered guide RNA comprises SEQ ID NO: 408. 146. The composition of embodiment 139, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 24 relative to position 0, and a combination thereof. 147. The composition of embodiment 146, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 394. 148. The composition of embodiment 147, wherein the engineered guide RNA comprises SEQ ID NO: 394. 149. The composition of embodiment 139, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 150. The composition of embodiment 146, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 482. 151. The composition of embodiment 147, wherein the engineered guide RNA comprises SEQ ID NO: 482. 152. The composition of embodiment 139, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof 153. The composition of embodiment 152, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 375. 154. The composition of embodiment 153, wherein the engineered guide RNA comprises SEQ ID NO: 375. 155. The composition of embodiment 11, wherein the first 6/6 symmetric internal loop is at position −11 relative to position 0. 156. The composition of embodiment 155, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof 157. The composition of embodiment 156, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 365. 158. The composition of embodiment 157, wherein the engineered guide RNA comprises SEQ ID NO: 365. 159. The composition of embodiment 155, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 160. The composition of embodiment 159, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 356. 161. The composition of embodiment 160, wherein the engineered guide RNA comprises SEQ ID NO: 356. 162. The composition of embodiment 155, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 41 relative to position 0, and a combination thereof. 163. The composition of embodiment 162, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 352. 164. The composition of embodiment 163, wherein the engineered guide RNA comprises SEQ ID NO: 352. 165. The composition of embodiment 155, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof 166. The composition of embodiment 165, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 252. 167. The composition of embodiment 166, wherein the engineered guide RNA comprises SEQ ID NO: 252. 168. The composition of embodiment 155, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 28 relative to position 0, and a combination thereof. 169. The composition of embodiment 168, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 291. 170. The composition of embodiment 169, wherein the engineered guide RNA comprises SEQ ID NO: 291. 171. The composition of any one of embodiments 6-9, wherein position 3 of ATTAAA is the target adenosine, wherein position 3 is the second A of ATTAAA from the 5′ end. 172. The composition of embodiment 171, wherein the one or more structural features comprises: a first 6/6 symmetric internal loop at a position selected from the group consisting of: 22, 21, 20, −2, −4, −5, −6, −7, −8, −9, and −10 relative to position 0 of ATTAAA. 173. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position 22 relative to position 0. 174. The composition of embodiment 173, wherein the one or more structural features further comprises an A/C mismatch at position 3 relative to position 0. 175. The composition of embodiment 174, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 17. 176. The composition of embodiment 175, wherein the engineered guide RNA comprises SEQ ID NO: 17. 177. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position 21 relative to position 0. 178. The composition of embodiment 177, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 15. 179. The composition of embodiment 178, wherein the engineered guide RNA comprises SEQ ID NO: 15. 180. The composition of embodiment 177, wherein the one or more structural features further comprises an A/C mismatch at position 5 relative to position 0. 181. The composition of embodiment 180, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 14. 182. The composition of embodiment 181, wherein the engineered guide RNA comprises SEQ ID NO: 14. 183. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position 20 relative to position 0. 184. The composition of embodiment 183, wherein the one or more structural features further comprises an A/C mismatch at position 5 relative to position 0. 185. The composition of embodiment 184, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 10. 186. The composition of embodiment 185, wherein the engineered guide RNA comprises SEQ ID NO: 10. 187. The composition of embodiment 183, wherein the one or more structural features further comprises an A/C mismatch at position 3 relative to position 0. 188. The composition of embodiment 187, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 8. 189. The composition of embodiment 188, wherein the engineered guide RNA comprises SEQ ID NO: 8. 190. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −2 relative to position 0. 191. The composition of embodiment 190, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 192. The composition of embodiment 191, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1411. 193. The composition of embodiment 192, wherein the engineered guide RNA comprises SEQ ID NO: 1411. 194. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −4 relative to position 0. 195. The composition of embodiment 194, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 22 relative to position 0. 196. The composition of embodiment 195, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1116. 197. The composition of embodiment 196, wherein the engineered guide RNA comprises SEQ ID NO: 1116. 198. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −5 relative to position 0. 199. The composition of embodiment 198, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 22 relative to position 0, and a combination thereof. 200. The composition of embodiment 199, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1002. 201. The composition of embodiment 200, wherein the engineered guide RNA comprises SEQ ID NO: 1002. 202. The composition of embodiment 198, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 33 relative to position 0. 203. The composition of embodiment 202, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. 204. The composition of embodiment 203, wherein the engineered guide RNA comprises SEQ ID NO: 1054. 205. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −6 relative to position 0. 206. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 24 relative to position 0, and a combination thereof. 207. The composition of embodiment 206, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 892. 208. The composition of embodiment 207, wherein the engineered guide RNA comprises SEQ ID NO: 892. 209. The composition of embodiment 205, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 21 relative to position 0. 210. The composition of embodiment 209, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 880. 211. The composition of embodiment 210, wherein the engineered guide RNA comprises SEQ ID NO: 880. 212. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof 213. The composition of embodiment 212, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 977. 214. The composition of embodiment 213, wherein the engineered guide RNA comprises SEQ ID NO: 977. 215. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof 216. The composition of embodiment 215, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 874. 217. The composition of embodiment 216, wherein the engineered guide RNA comprises SEQ ID NO: 874. 218. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof 219. The composition of embodiment 218, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 873. 220. The composition of embodiment 219, wherein the engineered guide RNA comprises SEQ ID NO: 873. 221. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 45 relative to position 0, a 5/5 symmetric internal loop at position 56 relative to position 0, a 5/5 symmetric internal loop at position 67 relative to position 0, and any combination thereof. 222. The composition of embodiment 221, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. 223. The composition of embodiment 222, wherein the engineered guide RNA comprises SEQ ID NO: 1569. 224. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. 225. The composition of embodiment 224, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. 226. The composition of embodiment 225, wherein the engineered guide RNA comprises SEQ ID NO: 1567. 227. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 55 relative to position 0, a 3/3 symmetric bulge at position 74 relative to position 0, and any combination thereof. 228. The composition of embodiment 227, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1587. 229. The composition of embodiment 228, wherein the engineered guide RNA comprises SEQ ID NO: 1587. 230. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 47 relative to position 0, a 3/3 symmetric bulge at position 58 relative to position 0, a 3/3 symmetric bulge at position 69 relative to position 0, and any combination thereof. 231. The composition of embodiment 230, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1571. 232. The composition of embodiment 231, wherein the engineered guide RNA comprises SEQ ID NO: 1571. 233. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 53 relative to position 0, a 5/5 symmetric internal loop at position 72 relative to position 0, and any combination thereof. 234. The composition of embodiment 233, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1585. 235. The composition of embodiment 234, wherein the engineered guide RNA comprises SEQ ID NO: 1585. 236. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 47 relative to position 0, a 5/5 symmetric internal loop at position 60 relative to position 0, a 5/5 symmetric internal loop at position 73 relative to position 0, and any combination thereof. 237. The composition of embodiment 236, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. 238. The composition of embodiment 237, wherein the engineered guide RNA comprises SEQ ID NO: 1573. 239. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. 240. The composition of embodiment 239, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. 241. The composition of embodiment 240, wherein the engineered guide RNA comprises SEQ ID NO: 1588. 242. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: A/C mismatch at position 3, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. 243. The composition of embodiment 242, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. 244. The composition of embodiment 243, wherein the engineered guide RNA comprises SEQ ID NO: 1575. 245. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 53 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 246. The composition of embodiment 245, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1584. 247. The composition of embodiment 246, wherein the engineered guide RNA comprises SEQ ID NO: 1584. 248. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 47 relative to position 0, a 4/4 symmetric bulge at position 59 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 249. The composition of embodiment 248, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1572. 250. The composition of embodiment 249, wherein the engineered guide RNA comprises SEQ ID NO: 1572. 251. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 47 relative to position 0, a 2/2 symmetric bulge at position 57 relative to position 0, a 2/2 symmetric bulge at position 67 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 252. The composition of embodiment 251, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1570. 253. The composition of embodiment 252, wherein the engineered guide RNA comprises SEQ ID NO: 1570. 254. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 49 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 255. The composition of embodiment 254, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1574. 256. The composition of embodiment 255, wherein the engineered guide RNA comprises SEQ ID NO: 1574. 257. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 51 relative to position 0, a 5/5 symmetric internal loop at position 68 relative to position 0, and any combination thereof. 258. The composition of embodiment 257, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1581. 259. The composition of embodiment 258, wherein the engineered guide RNA comprises SEQ ID NO: 1581. 260. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 45 relative to position 0, a 2/2 symmetric bulge at position 53 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 69 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 261. The composition of embodiment 260, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1566. 262. The composition of embodiment 261, wherein the engineered guide RNA comprises SEQ ID NO: 1566. 263. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 45 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 65 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. 264. The composition of embodiment 263, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1568. 265. The composition of embodiment 264, wherein the engineered guide RNA comprises SEQ ID NO: 1568. 266. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 51 relative to position 0, a 4/4 symmetric bulge at position 67 relative to position 0, and any combination thereof. 267. The composition of embodiment 266, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1580. 268. The composition of embodiment 267, wherein the engineered guide RNA comprises SEQ ID NO: 1580. 269. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 55 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 270. The composition of embodiment 269, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1586. 271. The composition of embodiment 270, wherein the engineered guide RNA comprises SEQ ID NO: 1586. 272. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 51 relative to position 0, a 2/2 symmetric bulge at position 65 relative to position 0, and any combination thereof. 273. The composition of embodiment 272, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1578. 274. The composition of embodiment 273, wherein the engineered guide RNA comprises SEQ ID NO: 1578. 275. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 51 relative to position 0, a 3/3 symmetric bulge at position 66 relative to position 0, and any combination thereof. 276. The composition of embodiment 275, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1579. 277. The composition of embodiment 276, wherein the engineered guide RNA comprises SEQ ID NO: 1579. 278. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 49 relative to position 0, a 5/5 symmetric internal loop at position 64 relative to position 0, and any combination thereof. 279. The composition of embodiment 278, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1577. 280. The composition of embodiment 279, wherein the engineered guide RNA comprises SEQ ID NO: 1577. 281. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 22 relative to position 0, and a combination thereof. 282. The composition of embodiment 281, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 884. 283. The composition of embodiment 282, wherein the engineered guide RNA comprises SEQ ID NO: 884. 284. The composition of embodiment 205, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof. 285. The composition of embodiment 284, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 871. 286. The composition of embodiment 285, wherein the engineered guide RNA comprises SEQ ID NO: 871. 287. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −7 relative to position 0. 288. The composition of embodiment 287, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof 289. The composition of embodiment 288, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 747. 290. The composition of embodiment 289, wherein the engineered guide RNA comprises SEQ ID NO: 747. 291. The composition of embodiment 287, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 22 relative to position 0, and a combination thereof. 292. The composition of embodiment 291, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 757. 293. The composition of embodiment 292, wherein the engineered guide RNA comprises SEQ ID NO: 757. 294. The composition of embodiment 287, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof. 295. The composition of embodiment 294, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 748. 296. The composition of embodiment 295, wherein the engineered guide RNA comprises SEQ ID NO: 748. 297. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −8 relative to position 0. 298. The composition of embodiment 297, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: A/C mismatch at position 5, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof. 299. The composition of embodiment 298, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 625. 300. The composition of embodiment 299, wherein the engineered guide RNA comprises SEQ ID NO: 625. 301. The composition of embodiment 297, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 22 relative to position 0, and a combination thereof. 302. The composition of embodiment 301, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 635. 303. The composition of embodiment 302, wherein the engineered guide RNA comprises SEQ ID NO: 635. 304. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −9 relative to position 0. 305. The composition of embodiment 304, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 20 relative to position 0, and a combination thereof. 306. The composition of embodiment 305, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 505. 307. The composition of embodiment 306, wherein the engineered guide RNA comprises SEQ ID NO: 505. 308. The composition of embodiment 304, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 42 relative to position 0. 309. The composition of embodiment 308, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 606. 310. The composition of embodiment 309, wherein the engineered guide RNA comprises SEQ ID NO: 606. 311. The composition of embodiment 304, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. 312. The composition of embodiment 311, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 593. 313. The composition of embodiment 312, wherein the engineered guide RNA comprises SEQ ID NO: 593. 314. The composition of embodiment 172, wherein the first 6/6 symmetric internal loop is at position −10 relative to position 0. 315. The composition of embodiment 314, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 42 relative to position 0. 316. The composition of embodiment 315, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 486. 317. The composition of embodiment 316, wherein the engineered guide RNA comprises SEQ ID NO: 486. 318. The composition of embodiment 314, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof. 319. The composition of embodiment 318, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 494. 320. The composition of embodiment 319, wherein the engineered guide RNA comprises SEQ ID NO: 494. 321. The composition of embodiment 171, wherein the one or more structural features comprises: a first 2/2 symmetric bulge at a position selected from the group consisting of: −3, −5, and −7 relative to position 0 of ATTAAA. 322. The composition of embodiment 321, wherein the first 2/2 symmetric bulge is at position −3 relative to position 0. 323. The composition of embodiment 322, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: a 2/2 symmetric bulge at position 14 relative to position 0, a 2/2 symmetric bulge at position 32 relative to position 0, a 2/2 symmetric bulge at position 50 relative to position 0, a 2/2 symmetric bulge at position 68 relative to position 0, and any combination thereof. 324. The composition of embodiment 323, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1552. 325. The composition of embodiment 324, wherein the engineered guide RNA comprises SEQ ID NO: 1552. 326. The composition of embodiment 321, wherein the first 2/2 symmetric bulge is at position −5 relative to position 0. 327. The composition of embodiment 326, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: a 2/2 symmetric bulge at position 26 relative to position 0, a 2/2 symmetric bulge at position 42 relative to position 0, a 2/2 symmetric bulge at position 58 relative to position 0, a 2/2 symmetric bulge at position 74 relative to position 0, and any combination thereof. 328. The composition of embodiment 327, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1545. 329. The composition of embodiment 328, wherein the engineered guide RNA comprises SEQ ID NO: 1545. 330. The composition of embodiment 321, wherein the first 2/2 symmetric bulge is at position −7 relative to position 0. 331. The composition of embodiment 330, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: a 2/2 symmetric bulge at position 6 relative to position 0, a 2/2 symmetric bulge at position 20 relative to position 0, a 2/2 symmetric bulge at position 34 relative to position 0, a 2/2 symmetric bulge at position 48 relative to position 0, a 2/2 symmetric bulge at position 62 relative to position 0, a 2/2 symmetric bulge at position 76 relative to position 0, and any combination thereof. 332. The composition of embodiment 331, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1538. 333. The composition of embodiment 332, wherein the engineered guide RNA comprises SEQ ID NO: 1538. 334. The composition of embodiment 171, wherein the one or more structural features comprises: a first 3/3 symmetric bulge at position −6 relative to position 0 of ATTAAA. 335. The composition of embodiment 334, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: a 3/3 symmetric bulge at position 7 relative to position 0, a 3/3 symmetric bulge at position 22 relative to position 0, a 3/3 symmetric bulge at position 37 relative to position 0, a 3/3 symmetric bulge at position 52 relative to position 0, a 3/3 symmetric bulge at position 67 relative to position 0, and any combination thereof. 336. The composition of embodiment 335, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1539. 337. The composition of embodiment 336, wherein the engineered guide RNA comprises SEQ ID NO: 1539. 338. The composition of any one of embodiments 6-9, wherein position 4 of ATTAAA is the target adenosine, wherein position 4 is the third A of ATTAAA from the 5′ end. 339. The composition of embodiment 338, wherein the one or more structural features comprises: a first 6/6 symmetric internal loop at a position selected from the group consisting of: 33, −1, −2, −3, −4, −5, −6, −7, −8, −9, −11, and −12 relative to position 0 of ATTAAA. 340. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position 33 relative to position 0. 341. The composition of embodiment 340, wherein the one or more structural features further comprises an A/C mismatch at position 3 relative to position 0. 342. The composition of embodiment 341, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 72. 343. The composition of embodiment 342, wherein the engineered guide RNA comprises SEQ ID NO: 72. 344. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −1 relative to position 0. 345. The composition of embodiment 344, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof 346. The composition of embodiment 345, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1463. 347. The composition of embodiment 346, wherein the engineered guide RNA comprises SEQ ID NO: 1463. 348. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −2 relative to position 0. 349. The composition of embodiment 348, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 32 relative to position 0. 350. The composition of embodiment 349, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1374. 351. The composition of embodiment 350, wherein the engineered guide RNA comprises SEQ ID NO: 1374. 352. The composition of embodiment 348, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 37 relative to position 0, and a combination thereof 353. The composition of embodiment 352, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1391. 354. The composition of embodiment 353, wherein the engineered guide RNA comprises SEQ ID NO: 1391. 355. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −3 relative to position 0. 356. The composition of embodiment 355, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. 357. The composition of embodiment 356, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1293. 358. The composition of embodiment 357, wherein the engineered guide RNA comprises SEQ ID NO: 1293. 359. The composition of embodiment 355, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. 360. The composition of embodiment 359, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1294. 361. The composition of embodiment 360, wherein the engineered guide RNA comprises SEQ ID NO: 1294. 362. The composition of embodiment 355, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 36 relative to position 0. 363. The composition of embodiment 362, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1296. 364. The composition of embodiment 363, wherein the engineered guide RNA comprises SEQ ID NO: 1296. 365. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −4 relative to position 0. 366. The composition of embodiment 365, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof 367. The composition of embodiment 366, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1183. 368. The composition of embodiment 367, wherein the engineered guide RNA comprises SEQ ID NO: 1183. 369. The composition of embodiment 365, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 38 relative to position 0, and a combination thereof 370. The composition of embodiment 369, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1193. 371. The composition of embodiment 370, wherein the engineered guide RNA comprises SEQ ID NO: 1193. 372. The composition of embodiment 365, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof 373. The composition of embodiment 372, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1212. 374. The composition of embodiment 373, wherein the engineered guide RNA comprises SEQ ID NO: 1212. 375. The composition of embodiment 365, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof 376. The composition of embodiment 375, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1168. 377. The composition of embodiment 376, wherein the engineered guide RNA comprises SEQ ID NO: 1168. 378. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −5 relative to position 0. 379. The composition of embodiment 378, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. 380. The composition of embodiment 379, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1066. 381. The composition of embodiment 380, wherein the engineered guide RNA comprises SEQ ID NO: 1066. 382. The composition of embodiment 378, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof. 383. The composition of embodiment 382, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1051. 384. The composition of embodiment 383, wherein the engineered guide RNA comprises SEQ ID NO: 1051. 385. The composition of embodiment 378, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 34 relative to position 0. 386. The composition of embodiment 385, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1059. 387. The composition of embodiment 386, wherein the engineered guide RNA comprises SEQ ID NO: 1059. 388. The composition of embodiment 378, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 33 relative to position 0. 389. The composition of embodiment 388, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. 390. The composition of embodiment 389, wherein the engineered guide RNA comprises SEQ ID NO: 1054. 391. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −6 relative to position 0. 392. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. 393. The composition of embodiment 392, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 967. 394. The composition of embodiment 393, wherein the engineered guide RNA comprises SEQ ID NO: 967. 395. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. 396. The composition of embodiment 395, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 930. 397. The composition of embodiment 396, wherein the engineered guide RNA comprises SEQ ID NO: 930. 398. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof 399. The composition of embodiment 398, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 934. 400. The composition of embodiment 399, wherein the engineered guide RNA comprises SEQ ID NO: 934. 401. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 35 relative to position 0, and a combination thereof. 402. The composition of embodiment 401, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 944. 403. The composition of embodiment 402, wherein the engineered guide RNA comprises SEQ ID NO: 944. 404. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 47 relative to position 0, a 5/5 symmetric internal loop at position 60 relative to position 0, a 5/5 symmetric internal loop at position 73 relative to position 0, and any combination thereof. 405. The composition of embodiment 404, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. 406. The composition of embodiment 405, wherein the engineered guide RNA comprises SEQ ID NO: 1573. 407. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. 408. The composition of embodiment 407, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. 409. The composition of embodiment 408, wherein the engineered guide RNA comprises SEQ ID NO: 1575. 410. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. 411. The composition of embodiment 410, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. 412. The composition of embodiment 411, wherein the engineered guide RNA comprises SEQ ID NO: 1567. 413. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 45 relative to position 0, a 5/5 symmetric internal loop at position 56 relative to position 0, a 5/5 symmetric internal loop at position 67 relative to position 0, and any combination thereof. 414. The composition of embodiment 413, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. 415. The composition of embodiment 414, wherein the engineered guide RNA comprises SEQ ID NO: 1569. 416. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 47 relative to position 0, a 2/2 symmetric bulge at position 57 relative to position 0, a 2/2 symmetric bulge at position 67 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 417. The composition of embodiment 416, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1570. 418. The composition of embodiment 417, wherein the engineered guide RNA comprises SEQ ID NO: 1570. 419. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 45 relative to position 0, a 2/2 symmetric bulge at position 53 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 69 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 420. The composition of embodiment 419, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1566. 421. The composition of embodiment 420, wherein the engineered guide RNA comprises SEQ ID NO: 1566. 422. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 47 relative to position 0, a 4/4 symmetric bulge at position 59 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 423. The composition of embodiment 422, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1572. 424. The composition of embodiment 423, wherein the engineered guide RNA comprises SEQ ID NO: 1572. 425. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 55 relative to position 0, a 3/3 symmetric bulge at position 74 relative to position 0, and any combination thereof. 426. The composition of embodiment 425, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1587. 427. The composition of embodiment 426, wherein the engineered guide RNA comprises SEQ ID NO: 1587. 428. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 47 relative to position 0, a 3/3 symmetric bulge at position 58 relative to position 0, a 3/3 symmetric bulge at position 69 relative to position 0, and any combination thereof. 429. The composition of embodiment 428, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1571. 430. The composition of embodiment 429, wherein the engineered guide RNA comprises SEQ ID NO: 1571. 431. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 49 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 432. The composition of embodiment 431, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1574. 433. The composition of embodiment 432, wherein the engineered guide RNA comprises SEQ ID NO: 1574. 434. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 53 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 435. The composition of embodiment 434, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1584. 436. The composition of embodiment 435, wherein the engineered guide RNA comprises SEQ ID NO: 1584. 437. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. 438. The composition of embodiment 437, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. 439. The composition of embodiment 438, wherein the engineered guide RNA comprises SEQ ID NO: 1588. 440. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 55 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 441. The composition of embodiment 440, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1586. 442. The composition of embodiment 441, wherein the engineered guide RNA comprises SEQ ID NO: 1586. 443. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 53 relative to position 0, a 5/5 symmetric internal loop at position 72 relative to position 0, and any combination thereof. 444. The composition of embodiment 443, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1585. 445. The composition of embodiment 444, wherein the engineered guide RNA comprises SEQ ID NO: 1585. 446. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 51 relative to position 0, a 5/5 symmetric internal loop at position 68 relative to position 0, and any combination thereof. 447. The composition of embodiment 446, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1581. 448. The composition of embodiment 447, wherein the engineered guide RNA comprises SEQ ID NO: 1581. 449. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 51 relative to position 0, a 2/2 symmetric bulge at position 65 relative to position 0, and any combination thereof. 450. The composition of embodiment 449, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1578. 451. The composition of embodiment 450, wherein the engineered guide RNA comprises SEQ ID NO: 1578. 452. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 53 relative to position 0, a 2/2 symmetric bulge at position 69 relative to position 0, and any combination thereof. 453. The composition of embodiment 452, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1582. 454. The composition of embodiment 453, wherein the engineered guide RNA comprises SEQ ID NO: 1582. 455. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 51 relative to position 0, a 4/4 symmetric bulge at position 67 relative to position 0, and any combination thereof. 456. The composition of embodiment 455, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1580. 457. The composition of embodiment 456, wherein the engineered guide RNA comprises SEQ ID NO: 1580. 458. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 49 relative to position 0, a 5/5 symmetric internal loop at position 64 relative to position 0, and any combination thereof. 459. The composition of embodiment 458, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1577. 460. The composition of embodiment 459, wherein the engineered guide RNA comprises SEQ ID NO: 1577. 461. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 45 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 65 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. 462. The composition of embodiment 461, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1568. 463. The composition of embodiment 462, wherein the engineered guide RNA comprises SEQ ID NO: 1568. 464. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 51 relative to position 0, a 3/3 symmetric bulge at position 66 relative to position 0, and any combination thereof. 465. The composition of embodiment 464, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1579. 466. The composition of embodiment 465, wherein the engineered guide RNA comprises SEQ ID NO: 1579. 467. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 53 relative to position 0, a 3/3 symmetric bulge at position 70 relative to position 0, and any combination thereof. 468. The composition of embodiment 467, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1583. 469. The composition of embodiment 468, wherein the engineered guide RNA comprises SEQ ID NO: 1583. 470. The composition of embodiment 391, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 49 relative to position 0, a 4/4 symmetric bulge at position 63 relative to position 0, and any combination thereof. 471. The composition of embodiment 470, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1576. 472. The composition of embodiment 471, wherein the engineered guide RNA comprises SEQ ID NO: 1576. 473. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −7 relative to position 0. 474. The composition of embodiment 473, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 34 relative to position 0, and a combination thereof. 475. The composition of embodiment 474, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 815. 476. The composition of embodiment 475, wherein the engineered guide RNA comprises SEQ ID NO: 815. 477. The composition of embodiment 473, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof 478. The composition of embodiment 477, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 806. 479. The composition of embodiment 478, wherein the engineered guide RNA comprises SEQ ID NO: 806. 480. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −8 relative to position 0. 481. The composition of embodiment 480, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 35 relative to position 0, and a combination thereof. 482. The composition of embodiment 481, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 694. 483. The composition of embodiment 482, wherein the engineered guide RNA comprises SEQ ID NO: 694. 484. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −9 relative to position 0. 485. The composition of embodiment 484, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. 486. The composition of embodiment 485, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 593. 487. The composition of embodiment 486, wherein the engineered guide RNA comprises SEQ ID NO: 593. 488. The composition of embodiment 484, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 34 relative to position 0, and a combination thereof 489. The composition of embodiment 488, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 566. 490. The composition of embodiment 489, wherein the engineered guide RNA comprises SEQ ID NO: 566. 491. The composition of embodiment 484, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof 492. The composition of embodiment 491, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 594. 493. The composition of embodiment 492, wherein the engineered guide RNA comprises SEQ ID NO: 594. 494. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −11 relative to position 0. 495. The composition of embodiment 494, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 496. The composition of embodiment 495, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 358. 497. The composition of embodiment 496, wherein the engineered guide RNA comprises SEQ ID NO: 358. 498. The composition of embodiment 339, wherein the first 6/6 symmetric internal loop is at position −12 relative to position 0. 499. The composition of embodiment 498, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof 500. The composition of embodiment 499, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 195. 501. The composition of embodiment 500, wherein the engineered guide RNA comprises SEQ ID NO: 195. 502. The composition of any one of embodiments 6-9, wherein position 5 of ATTAAA is the target adenosine, wherein position 5 is the forth A of ATTAAA from the 5′ end. 503. The composition of embodiment 340, wherein the one or more structural features comprises: a first 6/6 symmetric internal loop at a position selected from the group consisting of: 33, 23, −1, −2, −3, −4, −5, −6, −7, −8, −9, −10, and −12 relative to position 0 of ATTAAA. 504. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position 33 relative to position 0. 505. The composition of embodiment 504, wherein the one or more structural features further comprises an A/C mismatch at position 3 relative to position 0. 506. The composition of embodiment 505, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 72. 507. The composition of embodiment 506, wherein the engineered guide RNA comprises SEQ ID NO: 72. 508. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position 23 relative to position 0. 509. The composition of embodiment 508, wherein the one or more structural features further comprises an A/C mismatch at position 5 relative to position 0. 510. The composition of embodiment 509, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 24. 511. The composition of embodiment 510, wherein the engineered guide RNA comprises SEQ ID NO: 24. 512. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −1 relative to position 0. 513. The composition of embodiment 512, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 4 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. 514. The composition of embodiment 513, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1463. 515. The composition of embodiment 514, wherein the engineered guide RNA comprises SEQ ID NO: 1463. 516. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −2 relative to position 0. 517. The composition of embodiment 516, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 518. The composition of embodiment 517, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1411. 519. The composition of embodiment 518, wherein the engineered guide RNA comprises SEQ ID NO: 1411. 520. The composition of embodiment 516, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 37 relative to position 0, and a combination thereof. 521. The composition of embodiment 520, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1391. 522. The composition of embodiment 521, wherein the engineered guide RNA comprises SEQ ID NO: 1391. 523. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −3 relative to position 0. 524. The composition of embodiment 523, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof 525. The composition of embodiment 524, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1293. 526. The composition of embodiment 525, wherein the engineered guide RNA comprises SEQ ID NO: 1293. 527. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −4 relative to position 0. 528. The composition of embodiment 527, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. 529. The composition of embodiment 528, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1185. 530. The composition of embodiment 529, wherein the engineered guide RNA comprises SEQ ID NO: 1185. 531. The composition of embodiment 527, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. 532. The composition of embodiment 531, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1163. 533. The composition of embodiment 532, wherein the engineered guide RNA comprises SEQ ID NO: 1163. 534. The composition of embodiment 527, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. 535. The composition of embodiment 534, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1183. 536. The composition of embodiment 535, wherein the engineered guide RNA comprises SEQ ID NO: 1183. 537. The composition of embodiment 527, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 42 relative to position 0, and a combination thereof. 538. The composition of embodiment 537, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1212. 539. The composition of embodiment 538, wherein the engineered guide RNA comprises SEQ ID NO: 1212. 540. The composition of embodiment 527, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof. 541. The composition of embodiment 540, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1168. 542. The composition of embodiment 541, wherein the engineered guide RNA comprises SEQ ID NO: 1168. 543. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −5 relative to position 0. 544. The composition of embodiment 543, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 36 relative to position 0, and a combination thereof. 545. The composition of embodiment 544, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1066. 546. The composition of embodiment 545, wherein the engineered guide RNA comprises SEQ ID NO: 1066. 547. The composition of embodiment 543, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 34 relative to position 0, and a combination thereof. 548. The composition of embodiment 547, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1058. 549. The composition of embodiment 548, wherein the engineered guide RNA comprises SEQ ID NO: 1058. 550. The composition of embodiment 543, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof. 551. The composition of embodiment 550, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1051. 552. The composition of embodiment 551, wherein the engineered guide RNA comprises SEQ ID NO: 1051. 553. The composition of embodiment 543, wherein the one or more structural features further comprises a second 6/6 symmetric internal loop at position 33 relative to position 0. 554. The composition of embodiment 553, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1054. 555. The composition of embodiment 554, wherein the engineered guide RNA comprises SEQ ID NO: 1054. 556. The composition of embodiment 543, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 44 relative to position 0, and a combination thereof 557. The composition of embodiment 556, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1104. 558. The composition of embodiment 557, wherein the engineered guide RNA comprises SEQ ID NO: 1104. 559. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −6 relative to position 0. 560. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. 561. The composition of embodiment 560, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 930. 562. The composition of embodiment 561, wherein the engineered guide RNA comprises SEQ ID NO: 930. 563. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 35 relative to position 0, and a combination thereof 564. The composition of embodiment 563, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 944. 565. The composition of embodiment 564, wherein the engineered guide RNA comprises SEQ ID NO: 944. 566. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof 567. The composition of embodiment 566, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 935. 568. The composition of embodiment 567, wherein the engineered guide RNA comprises SEQ ID NO: 935. 569. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 49 relative to position 0, a 3/3 symmetric bulge at position 62 relative to position 0, a 3/3 symmetric bulge at position 75 relative to position 0, and any combination thereof. 570. The composition of embodiment 569, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1575. 571. The composition of embodiment 570, wherein the engineered guide RNA comprises SEQ ID NO: 1575. 572. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 45 relative to position 0, a 3/3 symmetric bulge at position 54 relative to position 0, a 3/3 symmetric bulge at position 63 relative to position 0, a 3/3 symmetric bulge at position 72 relative to position 0, and any combination thereof. 573. The composition of embodiment 572, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1567. 574. The composition of embodiment 573, wherein the engineered guide RNA comprises SEQ ID NO: 1567. 575. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 47 relative to position 0, a 3/3 symmetric bulge at position 58 relative to position 0, a 3/3 symmetric bulge at position 69 relative to position 0, and any combination thereof. 576. The composition of embodiment 575, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1571. 577. The composition of embodiment 576, wherein the engineered guide RNA comprises SEQ ID NO: 1571. 578. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 55 relative to position 0, a 3/3 symmetric bulge at position 74 relative to position 0, and any combination thereof. 579. The composition of embodiment 578, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1587. 580. The composition of embodiment 579, wherein the engineered guide RNA comprises SEQ ID NO: 1587. 581. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 47 relative to position 0, a 2/2 symmetric bulge at position 57 relative to position 0, a 2/2 symmetric bulge at position 67 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 582. The composition of embodiment 581, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1570. 583. The composition of embodiment 582, wherein the engineered guide RNA comprises SEQ ID NO: 1570. 584. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 45 relative to position 0, a 2/2 symmetric bulge at position 53 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 69 relative to position 0, a 2/2 symmetric bulge at position 77 relative to position 0, and any combination thereof. 585. The composition of embodiment 584, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1566. 586. The composition of embodiment 585, wherein the engineered guide RNA comprises SEQ ID NO: 1566. 587. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 49 relative to position 0, a 2/2 symmetric bulge at position 61 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 588. The composition of embodiment 587, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1574. 589. The composition of embodiment 588, wherein the engineered guide RNA comprises SEQ ID NO: 1574. 590. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 51 relative to position 0, a 2/2 symmetric bulge at position 65 relative to position 0, and any combination thereof. 591. The composition of embodiment 590, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1578. 592. The composition of embodiment 591, wherein the engineered guide RNA comprises SEQ ID NO: 1578. 593. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 55 relative to position 0, a 2/2 symmetric bulge at position 73 relative to position 0, and any combination thereof. 594. The composition of embodiment 593, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1586. 595. The composition of embodiment 594, wherein the engineered guide RNA comprises SEQ ID NO: 1586. 596. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 2/2 symmetric bulge at position 53 relative to position 0, a 2/2 symmetric bulge at position 69 relative to position 0, and any combination thereof. 597. The composition of embodiment 596, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1582. 598. The composition of embodiment 597, wherein the engineered guide RNA comprises SEQ ID NO: 1582. 599. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 47 relative to position 0, a 5/5 symmetric internal loop at position 60 relative to position 0, a 5/5 symmetric internal loop at position 73 relative to position 0, and any combination thereof. 600. The composition of embodiment 599, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1573. 601. The composition of embodiment 600, wherein the engineered guide RNA comprises SEQ ID NO: 1573. 602. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 51 relative to position 0, a 5/5 symmetric internal loop at position 68 relative to position 0, and any combination thereof. 603. The composition of embodiment 602, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1581. 604. The composition of embodiment 603, wherein the engineered guide RNA comprises SEQ ID NO: 1581. 605. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 45 relative to position 0, a 5/5 symmetric internal loop at position 56 relative to position 0, a 5/5 symmetric internal loop at position 67 relative to position 0, and any combination thereof. 606. The composition of embodiment 605, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1569. 607. The composition of embodiment 606, wherein the engineered guide RNA comprises SEQ ID NO: 1569. 608. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 53 relative to position 0, a 5/5 symmetric internal loop at position 72 relative to position 0, and any combination thereof. 609. The composition of embodiment 608, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1585. 610. The composition of embodiment 609, wherein the engineered guide RNA comprises SEQ ID NO: 1585. 611. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 51 relative to position 0, a 4/4 symmetric bulge at position 67 relative to position 0, and any combination thereof. 612. The composition of embodiment 611, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1580. 613. The composition of embodiment 612, wherein the engineered guide RNA comprises SEQ ID NO: 1580. 614. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. 615. The composition of embodiment 614, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1588. 616. The composition of embodiment 615, wherein the engineered guide RNA comprises SEQ ID NO: 1588. 617. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 53 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 618. The composition of embodiment 617, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1584. 619. The composition of embodiment 618, wherein the engineered guide RNA comprises SEQ ID NO: 1584. 620. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 49 relative to position 0, a 4/4 symmetric bulge at position 63 relative to position 0, and any combination thereof. 621. The composition of embodiment 620, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1576. 622. The composition of embodiment 621, wherein the engineered guide RNA comprises SEQ ID NO: 1576. 623. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 47 relative to position 0, a 4/4 symmetric bulge at position 59 relative to position 0, a 4/4 symmetric bulge at position 71 relative to position 0, and any combination thereof. 624. The composition of embodiment 623, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1572. 625. The composition of embodiment 624, wherein the engineered guide RNA comprises SEQ ID NO: 1572. 626. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 4/4 symmetric bulge at position 45 relative to position 0, a 4/4 symmetric bulge at position 55 relative to position 0, a 4/4 symmetric bulge at position 65 relative to position 0, a 4/4 symmetric bulge at position 75 relative to position 0, and any combination thereof. 627. The composition of embodiment 626, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1568. 628. The composition of embodiment 627, wherein the engineered guide RNA comprises SEQ ID NO: 1568. 629. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 5/5 symmetric internal loop at position 49 relative to position 0, a 5/5 symmetric internal loop at position 64 relative to position 0, and any combination thereof. 630. The composition of embodiment 629, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1577. 631. The composition of embodiment 630, wherein the engineered guide RNA comprises SEQ ID NO: 1577. 632. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 51 relative to position 0, a 3/3 symmetric bulge at position 66 relative to position 0, and any combination thereof. 633. The composition of embodiment 632, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1579. 634. The composition of embodiment 633, wherein the engineered guide RNA comprises SEQ ID NO: 1579. 635. The composition of embodiment 559, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, a 3/3 symmetric bulge at position 53 relative to position 0, a 3/3 symmetric bulge at position 70 relative to position 0, and any combination thereof. 636. The composition of embodiment 635, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 1583. 637. The composition of embodiment 636, wherein the engineered guide RNA comprises SEQ ID NO: 1583. 638. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −7 relative to position 0. 639. The composition of embodiment 638, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof. 640. The composition of embodiment 639, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 810. 641. The composition of embodiment 640, wherein the engineered guide RNA comprises SEQ ID NO: 810. 642. The composition of embodiment 638, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 34 relative to position 0, and a combination thereof. 643. The composition of embodiment 642, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 815. 644. The composition of embodiment 643, wherein the engineered guide RNA comprises SEQ ID NO: 815. 645. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −8 relative to position 0. 646. The composition of embodiment 645, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 32 relative to position 0, and a combination thereof. 647. The composition of embodiment 646, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 680. 648. The composition of embodiment 647, wherein the engineered guide RNA comprises SEQ ID NO: 680. 649. The composition of embodiment 645, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 35 relative to position 0, and a combination thereof. 650. The composition of embodiment 649, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 694. 651. The composition of embodiment 650, wherein the engineered guide RNA comprises SEQ ID NO: 694. 652. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −9 relative to position 0. 653. The composition of embodiment 652, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 34 relative to position 0, and a combination thereof. 654. The composition of embodiment 653, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 566. 655. The composition of embodiment 654, wherein the engineered guide RNA comprises SEQ ID NO: 566. 656. The composition of embodiment 652, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 3 relative to position 0, a second 6/6 symmetric internal loop at position 40 relative to position 0, and a combination thereof. 657. The composition of embodiment 656, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 594. 658. The composition of embodiment 657, wherein the engineered guide RNA comprises SEQ ID NO: 594. 659. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −10 relative to position 0. 660. The composition of embodiment 659, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 23 relative to position 0, and a combination thereof. 661. The composition of embodiment 660, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 392. 662. The composition of embodiment 661, wherein the engineered guide RNA comprises SEQ ID NO: 392. 663. The composition of embodiment 503, wherein the first 6/6 symmetric internal loop is at position −12 relative to position 0. 664. The composition of embodiment 663, wherein the one or more structural features further comprises at least one structural feature selected from the group consisting of: an A/C mismatch at position 5 relative to position 0, a second 6/6 symmetric internal loop at position 33 relative to position 0, and a combination thereof 665. The composition of embodiment 664, wherein the engineered guide RNA comprises at least about: 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to SEQ ID NO: 195. 666. The composition of embodiment 665, wherein the engineered guide RNA comprises SEQ ID NO: 195. 667. The composition of any one of embodiments 10-666, further comprising editing at any A of ATTAAA. 668. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 669. The composition of embodiment 668, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 8. 670. The composition of any one of embodiments 668-669, wherein the engineered guide RNA has a sequence of SEQ ID NO: 8. 671. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 672. The composition of embodiment 671, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 10. 673. The composition of any one of embodiments 671-672, wherein the engineered guide RNA has a sequence of SEQ ID NO: 10. 674. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 675. The composition of embodiment 674, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 14. 676. The composition of any one of embodiments 674-675, wherein the engineered guide RNA has a sequence of SEQ ID NO: 14. 677. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 678. The composition of embodiment 677, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 15. 679. The composition of any one of embodiments 677-678, wherein the engineered guide RNA has a sequence of SEQ ID NO: 15. 680. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 681. The composition of embodiment 680, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 17. 682. The composition of any one of embodiments 680-681, wherein the engineered guide RNA has a sequence of SEQ ID NO: 17. 683. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 684. The composition of embodiment 683, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 24. 685. The composition of any one of embodiments 683-684, wherein the engineered guide RNA has a sequence of SEQ ID NO: 24. 686. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 687. The composition of embodiment 686, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 72. 688. The composition of any one of embodiments 686-687, wherein the engineered guide RNA has a sequence of SEQ ID NO: 72. 689. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 690. The composition of embodiment 689, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 195. 691. The composition of any one of embodiments 689-690, wherein the engineered guide RNA has a sequence of SEQ ID NO: 195. 692. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 693. The composition of embodiment 692, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 252. 694. The composition of any one of embodiments 692-693, wherein the engineered guide RNA has a sequence of SEQ ID NO: 252. 695. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 696. The composition of embodiment 695, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 291. 697. The composition of any one of embodiments 695-696, wherein the engineered guide RNA has a sequence of SEQ ID NO: 291. 698. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 699. The composition of embodiment 698, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 352. 700. The composition of any one of embodiments 698-699, wherein the engineered guide RNA has a sequence of SEQ ID NO: 352. 701. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 702. The composition of embodiment 701, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 356. 703. The composition of any one of embodiments 701-702, wherein the engineered guide RNA has a sequence of SEQ ID NO: 356. 704. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 705. The composition of embodiment 704, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 358. 706. The composition of any one of embodiments 704-705, wherein the engineered guide RNA has a sequence of SEQ ID NO: 358. 707. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 708. The composition of embodiment 707, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 365. 709. The composition of any one of embodiments 707-708, wherein the engineered guide RNA has a sequence of SEQ ID NO: 365. 710. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 711. The composition of embodiment 710, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 375. 712. The composition of any one of embodiments 710-711, wherein the engineered guide RNA has a sequence of SEQ ID NO: 375. 713. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 714. The composition of embodiment 713, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 392. 715. The composition of any one of embodiments 713-714, wherein the engineered guide RNA has a sequence of SEQ ID NO: 392. 716. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 717. The composition of embodiment 716, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 394. 718. The composition of any one of embodiments 716-717, wherein the engineered guide RNA has a sequence of SEQ ID NO: 394. 719. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 720. The composition of embodiment 719, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 408. 721. The composition of any one of embodiments 719-720, wherein the engineered guide RNA has a sequence of SEQ ID NO: 408. 722. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 723. The composition of embodiment 722, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 482. 724. The composition of any one of embodiments 722-723, wherein the engineered guide RNA has a sequence of SEQ ID NO: 482. 725. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 726. The composition of embodiment 725, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 486. 727. The composition of any one of embodiments 725-726, wherein the engineered guide RNA has a sequence of SEQ ID NO: 486. 728. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 729. The composition of embodiment 728, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 487. 730. The composition of any one of embodiments 728-729, wherein the engineered guide RNA has a sequence of SEQ ID NO: 487. 731. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 732. The composition of embodiment 731, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 494. 733. The composition of any one of embodiments 731-732, wherein the engineered guide RNA has a sequence of SEQ ID NO: 494. 734. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 735. The composition of embodiment 734, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 502. 736. The composition of any one of embodiments 734-735, wherein the engineered guide RNA has a sequence of SEQ ID NO: 502. 737. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 738. The composition of embodiment 737, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 505. 739. The composition of any one of embodiments 737-738, wherein the engineered guide RNA has a sequence of SEQ ID NO: 505. 740. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 741. The composition of embodiment 740, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 512. 742. The composition of any one of embodiments 740-741, wherein the engineered guide RNA has a sequence of SEQ ID NO: 512. 743. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 744. The composition of embodiment 743, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 566. 745. The composition of any one of embodiments 743-744, wherein the engineered guide RNA has a sequence of SEQ ID NO: 566. 746. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 747. The composition of embodiment 746, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 593. 748. The composition of any one of embodiments 746-747, wherein the engineered guide RNA has a sequence of SEQ ID NO: 593. 749. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 750. The composition of embodiment 749, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 594. 751. The composition of any one of embodiments 749-750, wherein the engineered guide RNA has a sequence of SEQ ID NO: 594. 752. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 753. The composition of embodiment 752, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 606. 754. The composition of any one of embodiments 752-753, wherein the engineered guide RNA has a sequence of SEQ ID NO: 606. 755. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 756. The composition of embodiment 755, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 625. 757. The composition of any one of embodiments 755-756, wherein the engineered guide RNA has a sequence of SEQ ID NO: 625. 758. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 759. The composition of embodiment 758, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 635. 760. The composition of any one of embodiments 758-759, wherein the engineered guide RNA has a sequence of SEQ ID NO: 635. 761. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 762. The composition of embodiment 761, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 642. 763. The composition of any one of embodiments 761-762, wherein the engineered guide RNA has a sequence of SEQ ID NO: 642. 764. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 765. The composition of embodiment 764, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 679. 766. The composition of any one of embodiments 764-765, wherein the engineered guide RNA has a sequence of SEQ ID NO: 679. 767. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 768. The composition of embodiment 767, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 680. 769. The composition of any one of embodiments 767-768, wherein the engineered guide RNA has a sequence of SEQ ID NO: 680. 770. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 771. The composition of embodiment 770, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 694. 772. The composition of any one of embodiments 770-771, wherein the engineered guide RNA has a sequence of SEQ ID NO: 694. 773. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 774. The composition of embodiment 773, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 727. 775. The composition of any one of embodiments 773-774, wherein the engineered guide RNA has a sequence of SEQ ID NO: 727. 776. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 777. The composition of embodiment 776, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 737. 778. The composition of any one of embodiments 776-777, wherein the engineered guide RNA has a sequence of SEQ ID NO: 737. 779. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 780. The composition of embodiment 779, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 747. 781. The composition of any one of embodiments 779-780, wherein the engineered guide RNA has a sequence of SEQ ID NO: 747. 782. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 783. The composition of embodiment 782, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 748. 784. The composition of any one of embodiments 782-783, wherein the engineered guide RNA has a sequence of SEQ ID NO: 748. 785. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 786. The composition of embodiment 785, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 757. 787. The composition of any one of embodiments 785-786, wherein the engineered guide RNA has a sequence of SEQ ID NO: 757. 788. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 789. The composition of embodiment 788, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 769. 790. The composition of any one of embodiments 788-789, wherein the engineered guide RNA has a sequence of SEQ ID NO: 769. 791. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 792. The composition of embodiment 791, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 806. 793. The composition of any one of embodiments 791-792, wherein the engineered guide RNA has a sequence of SEQ ID NO: 806. 794. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 795. The composition of embodiment 794, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 810. 796. The composition of any one of embodiments 794-795, wherein the engineered guide RNA has a sequence of SEQ ID NO: 810. 797. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 798. The composition of embodiment 797, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 815. 799. The composition of any one of embodiments 797-798, wherein the engineered guide RNA has a sequence of SEQ ID NO: 815. 800. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 801. The composition of embodiment 800, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 851. 802. The composition of any one of embodiments 800-801, wherein the engineered guide RNA has a sequence of SEQ ID NO: 851. 803. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 804. The composition of embodiment 803, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 871. 805. The composition of any one of embodiments 803-804, wherein the engineered guide RNA has a sequence of SEQ ID NO: 871. 806. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 807. The composition of embodiment 806, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 873. 808. The composition of any one of embodiments 806-807, wherein the engineered guide RNA has a sequence of SEQ ID NO: 873. 809. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 810. The composition of embodiment 809, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 874. 811. The composition of any one of embodiments 809-810, wherein the engineered guide RNA has a sequence of SEQ ID NO: 874. 812. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 813. The composition of embodiment 812, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 880. 814. The composition of any one of embodiments 812-813, wherein the engineered guide RNA has a sequence of SEQ ID NO: 880. 815. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 816. The composition of embodiment 815, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 884. 817. The composition of any one of embodiments 815-816, wherein the engineered guide RNA has a sequence of SEQ ID NO: 884. 818. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 819. The composition of embodiment 818, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 892. 820. The composition of any one of embodiments 818-819, wherein the engineered guide RNA has a sequence of SEQ ID NO: 892. 821. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 822. The composition of embodiment 821, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 906. 823. The composition of any one of embodiments 821-822, wherein the engineered guide RNA has a sequence of SEQ ID NO: 906. 824. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 825. The composition of embodiment 824, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 930. 826. The composition of any one of embodiments 824-825, wherein the engineered guide RNA has a sequence of SEQ ID NO: 930. 827. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 828. The composition of embodiment 827, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 934. 829. The composition of any one of embodiments 827-828, wherein the engineered guide RNA has a sequence of SEQ ID NO: 934. 830. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 831. The composition of embodiment 830, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 935. 832. The composition of any one of embodiments 830-831, wherein the engineered guide RNA has a sequence of SEQ ID NO: 935. 833. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 834. The composition of embodiment 833, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 937. 835. The composition of any one of embodiments 833-834, wherein the engineered guide RNA has a sequence of SEQ ID NO: 937. 836. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 837. The composition of embodiment 836, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 944. 838. The composition of any one of embodiments 836-837, wherein the engineered guide RNA has a sequence of SEQ ID NO: 944. 839. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 840. The composition of embodiment 839, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 967. 841. The composition of any one of embodiments 839-840, wherein the engineered guide RNA has a sequence of SEQ ID NO: 967. 842. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 843. The composition of embodiment 842, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 976. 844. The composition of any one of embodiments 842-843, wherein the engineered guide RNA has a sequence of SEQ ID NO: 976. 845. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 846. The composition of embodiment 845, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 977. 847. The composition of any one of embodiments 845-846, wherein the engineered guide RNA has a sequence of SEQ ID NO: 977. 848. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 849. The composition of embodiment 848, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 985. 850. The composition of any one of embodiments 848-849, wherein the engineered guide RNA has a sequence of SEQ ID NO: 985. 851. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 852. The composition of embodiment 851, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1002. 853. The composition of any one of embodiments 851-852, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1002. 854. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 855. The composition of embodiment 854, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1008. 856. The composition of any one of embodiments 854-855, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1008. 857. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 858. The composition of embodiment 857, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1051. 859. The composition of any one of embodiments 857-858, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1051. 860. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 861. The composition of embodiment 860, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1054. 862. The composition of any one of embodiments 860-861, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1054. 863. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 864. The composition of embodiment 863, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1058. 865. The composition of any one of embodiments 863-864, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1058. 866. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 867. The composition of embodiment 866, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1059. 868. The composition of any one of embodiments 866-867, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1059. 869. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 870. The composition of embodiment 869, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1066. 871. The composition of any one of embodiments 869-870, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1066. 872. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 873. The composition of embodiment 872, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1098. 874. The composition of any one of embodiments 872-873, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1098. 875. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 876. The composition of embodiment 875, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1103. 877. The composition of any one of embodiments 875-876, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1103. 878. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 879. The composition of embodiment 878, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1104. 880. The composition of any one of embodiments 878-879, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1104. 881. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 882. The composition of embodiment 881, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1116. 883. The composition of any one of embodiments 881-882, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1116. 884. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 885. The composition of embodiment 884, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1117. 886. The composition of any one of embodiments 884-885, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1117. 887. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 888. The composition of embodiment 887, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1163. 889. The composition of any one of embodiments 887-888, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1163. 890. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 891. The composition of embodiment 890, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1168. 892. The composition of any one of embodiments 890-891, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1168. 893. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 894. The composition of embodiment 893, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1183. 895. The composition of any one of embodiments 893-894, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1183. 896. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 897. The composition of embodiment 896, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1185. 898. The composition of any one of embodiments 896-897, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1185. 899. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 900. The composition of embodiment 899, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1193. 901. The composition of any one of embodiments 899-900, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1193. 902. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 903. The composition of embodiment 902, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1211. 904. The composition of any one of embodiments 902-903, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1211. 905. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 906. The composition of embodiment 905, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1212. 907. The composition of any one of embodiments 905-906, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1212. 908. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 909. The composition of embodiment 908, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1236. 910. The composition of any one of embodiments 908-909, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1236. 911. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 912. The composition of embodiment 911, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1293. 913. The composition of any one of embodiments 911-912, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1293. 914. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 915. The composition of embodiment 914, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1294. 916. The composition of any one of embodiments 914-915, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1294. 917. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 918. The composition of embodiment 917, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1296. 919. The composition of any one of embodiments 917-918, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1296. 920. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 921. The composition of embodiment 920, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1374. 922. The composition of any one of embodiments 920-921, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1374. 923. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 924. The composition of embodiment 923, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1391. 925. The composition of any one of embodiments 923-924, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1391. 926. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 927. The composition of embodiment 926, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1411. 928. The composition of any one of embodiments 926-927, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1411. 929. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 930. The composition of embodiment 929, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1463. 931. The composition of any one of embodiments 929-930, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1463. 932. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 933. The composition of embodiment 932, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1538. 934. The composition of any one of embodiments 932-933, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1538. 935. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 936. The composition of embodiment 935, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1539. 937. The composition of any one of embodiments 935-936, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1539. 938. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 939. The composition of embodiment 938, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1545. 940. The composition of any one of embodiments 938-939, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1545. 941. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 942. The composition of embodiment 941, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1552. 943. The composition of any one of embodiments 941-942, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1552. 944. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 945. The composition of embodiment 944, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1566. 946. The composition of any one of embodiments 944-945, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1566. 947. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 948. The composition of embodiment 947, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1567. 949. The composition of any one of embodiments 947-948, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1567. 950. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 951. The composition of embodiment 950, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1568. 952. The composition of any one of embodiments 950-951, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1568. 953. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 954. The composition of embodiment 953, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1569. 955. The composition of any one of embodiments 953-954, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1569. 956. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 957. The composition of embodiment 956, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1570. 958. The composition of any one of embodiments 956-957, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1570. 959. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 960. The composition of embodiment 959, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1571. 961. The composition of any one of embodiments 959-960, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1571. 962. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 963. The composition of embodiment 962, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1572. 964. The composition of any one of embodiments 962-963, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1572. 965. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 966. The composition of embodiment 965, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1573. 967. The composition of any one of embodiments 965-966, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1573. 968. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 969. The composition of embodiment 968, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1574. 970. The composition of any one of embodiments 968-969, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1574. 971. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 972. The composition of embodiment 971, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1575. 973. The composition of any one of embodiments 971-972, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1575. 974. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 975. The composition of embodiment 974, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1576. 976. The composition of any one of embodiments 974-975, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1576. 977. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 978. The composition of embodiment 977, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1577. 979. The composition of any one of embodiments 977-978, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1577. 980. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 981. The composition of embodiment 980, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1578. 982. The composition of any one of embodiments 980-981, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1578. 983. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 984. The composition of embodiment 983, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1579. 985. The composition of any one of embodiments 983-984, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1579. 986. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 987. The composition of embodiment 986, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1580. 988. The composition of any one of embodiments 986-987, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1580. 989. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 990. The composition of embodiment 989, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1581. 991. The composition of any one of embodiments 989-990, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1581. 992. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 993. The composition of embodiment 992, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1582. 994. The composition of any one of embodiments 992-993, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1582. 995. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 996. The composition of embodiment 995, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1583. 997. The composition of any one of embodiments 995-996, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1583. 998. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 999. The composition of embodiment 998, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1584. 1000. The composition of any one of embodiments 998-999, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1584. 1001. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 1002. The composition of embodiment 1001, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1585. 1003. The composition of any one of embodiments 1001-1002, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1585. 1004. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 1005. The composition of embodiment 1004, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1586. 1006. The composition of any one of embodiments 1004-1005, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1586. 1007. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 1008. The composition of embodiment 1007, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1587. 1009. The composition of any one of embodiments 1007-1008, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1587. 1010. The composition of embodiment 7, wherein the one or more structural features comprise a 1 nucleotide mismatch formed 3 nucleotides downstream (3′) from the target A, and a 6 nucleotide internal symmetric loop formed 20 nucleotides downstream (3′) from the target A. 1011. The composition of embodiment 1010, wherein the engineered guide RNA has at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to a guide RNA comprising SEQ ID NO: 1588. 1012. The composition of any one of embodiments 1010-1011, wherein the engineered guide RNA has a sequence of SEQ ID NO: 1588. 1013. The composition of any one of embodiments 6-8, wherein the one or more structural features comprise: a) a first 6/6 symmetric internal loop, and b) at least one additional structural feature selected from the group consisting of: a second 6/6 symmetric internal loop, a 5/5 symmetric internal loop, a 4/4 symmetric bulge, a 3/3 symmetric bulge, and a 2/2 symmetric bulge. 1014. The composition of embodiment 1013, wherein the guide-target RNA scaffold further comprises an A/C mismatch, wherein the cytosine of the A/C mismatch is present in the engineered guide RNA opposite the one or more target adenosines; and wherein the one or more structural features comprise: a) the first 6/6 symmetric internal loop positioned from position −4 to −8, relative to the A/C mismatch; b) the second 6/6 symmetric internal loop positioned from position+31 to +35, relative to the A/C mismatch. 1015. The composition of embodiment 1014, wherein the guide-target RNA scaffold further comprises an A/C mismatch, wherein the cytosine of the A/C mismatch is present in the engineered guide RNA opposite the one or more target adenosines; and wherein the one or more structural features comprise: a) the first 6/6 symmetric internal loop at position −6, relative to the A/C mismatch; b) the second 6/6 symmetric internal loop at position+33, relative to the A/C mismatch. 1016. The composition of embodiment 1014 or 1015, wherein the first 6/6 symmetric internal loop comprises the sequence GGAACU on the engineered guide RNA side, and the sequence UUCAGA on the target RNA side. 1017. The composition of embodiment 1014 or 1015, wherein the second 6/6 symmetric internal loop comprises the sequence CUGACC on the engineered guide RNA side, and the sequence AGAUUU on the target RNA side. 1018. The composition of any one of embodiments 6-8, wherein the one or more structural features comprise a first 6/6 symmetric internal loop and a second 6/6 symmetric internal loop and wherein each A in the target RNA is base paired to a U in the engineered guide RNA. 1019. The composition of any one of embodiments 6-8, wherein the engineered guide RNA comprises a sequence of any one of SEQ ID NO: 1566, SEQ ID NO: 1567, SEQ ID NO: 1569, SEQ ID NO: 1570, SEQ ID NO: 1571, SEQ ID NO: 1572, SEQ ID NO: 1573, SEQ ID NO: 1575, SEQ ID NO: 1577, SEQ ID NO: 1581, SEQ ID NO: 1585, SEQ ID NO: 1587, or SEQ ID NO: 1588. 1020. The composition of any one of embodiments 6-8, wherein the engineered guide RNA comprises a sequence of any one of SEQ ID NO: 1575, SEQ ID NO: 593, SEQ ID NO: 1573, SEQ ID NO: 934, SEQ ID NO: 1569, SEQ ID NO: 1567, SEQ ID NO: 851, SEQ ID NO: 1211, SEQ ID NO: 1571, SEQ ID NO: 937, SEQ ID NO: 1574, SEQ ID NO: 1570, SEQ ID NO: 1566, SEQ ID NO: 1117, SEQ ID NO: 906, SEQ ID NO: 1572, SEQ ID NO: 1104, SEQ ID NO: 352, SEQ ID NO: 512, SEQ ID NO: 1587, SEQ ID NO: 375, SEQ ID NO: 1588, SEQ ID NO: 977, SEQ ID NO: 642, SEQ ID NO: 1236, SEQ ID NO: 1584, SEQ ID NO: 252, SEQ ID NO: 394, SEQ ID NO: 482, SEQ ID NO: 1585, SEQ ID NO: 291, SEQ ID NO: 356, SEQ ID NO: 1054, SEQ ID NO: 1581, SEQ ID NO: 1103, SEQ ID NO: 502, SEQ ID NO: 769, SEQ ID NO: 408, SEQ ID NO: 1586, SEQ ID NO: 1008, SEQ ID NO: 737, SEQ ID NO: 985, SEQ ID NO: 679, SEQ ID NO: 727, SEQ ID NO: 1578, SEQ ID NO: 365, SEQ ID NO: 1580, SEQ ID NO: 487, SEQ ID NO: 1098, or SEQ ID NO: 976. 1021. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1575. 1022. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 593. 1023. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1573. 1024. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 934. 1025. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1569. 1026. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1567. 1027. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 851. 1028. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1211. 1029. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1571. 1030. The composition of embodiment 1020, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 937. 1031. The composition of any one of embodiments 6-8, wherein the engineered guide RNA comprises a sequence of any one of SEQ ID NO: 1573, SEQ ID NO: 1588, SEQ ID NO: 1545, SEQ ID NO: 1575, SEQ ID NO: 1569, SEQ ID NO: 1584, SEQ ID NO: 1572, SEQ ID NO: 1567, SEQ ID NO: 1570, SEQ ID NO: 1587, SEQ ID NO: 1574, SEQ ID NO: 625, SEQ ID NO: 1571, SEQ ID NO: 874, SEQ ID NO: 17, SEQ ID NO: 1585, SEQ ID NO: 757, SEQ ID NO: 1581, SEQ ID NO: 1538, SEQ ID NO: 8, SEQ ID NO: 1002, SEQ ID NO: 1566, SEQ ID NO: 486, SEQ ID NO: 1552, SEQ ID NO: 505, SEQ ID NO: 635, SEQ ID NO: 606, SEQ ID NO: 884, SEQ ID NO: 1054, SEQ ID NO: 880, SEQ ID NO: 1411, SEQ ID NO: 1568, SEQ ID NO: 871, SEQ ID NO: 1580, SEQ ID NO: 1539, SEQ ID NO: 14, SEQ ID NO: 892, SEQ ID NO: 1116, SEQ ID NO: 15, SEQ ID NO: 1586, SEQ ID NO: 593, SEQ ID NO: 10, SEQ ID NO: 977, SEQ ID NO: 1578, SEQ ID NO: 1579, SEQ ID NO: 747, SEQ ID NO: 1577, 748, SEQ ID NO: 873, or SEQ ID NO: 494. 1032. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1573. 1033. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1588. 1034. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1545. 1035. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1575. 1036. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1569. 1037. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1584. 1038. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1572. 1039. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1567. 1040. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1570. 1041. The composition of embodiment 1031, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1587. 1042. The composition of any one of embodiments 6-8, wherein the engineered guide RNA comprises a sequence of any one of SEQ ID NO: 1575, SEQ ID NO: 1573, SEQ ID NO: 1567, SEQ ID NO: 1569, SEQ ID NO: 1570, SEQ ID NO: 1566, SEQ ID NO: 1572, SEQ ID NO: 1587, SEQ ID NO: 1571, SEQ ID NO: 1574, SEQ ID NO: 1584, SEQ ID NO: 1588, SEQ ID NO: 1054, SEQ ID NO: 1586, SEQ ID NO: 1585, SEQ ID NO: 1581, SEQ ID NO: 1578, SEQ ID NO: 1580, SEQ ID NO: 934, SEQ ID NO: 72, SEQ ID NO: 1582, SEQ ID NO: 1066, SEQ ID NO: 1183, SEQ ID NO: 1577, SEQ ID NO: 967, SEQ ID NO: 1568, SEQ ID NO: 930, SEQ ID NO: 566, SEQ ID NO: 1463, SEQ ID NO: 1294, SEQ ID NO: 1293, SEQ ID NO: 1391, SEQ ID NO: 1579, SEQ ID NO: 1583, SEQ ID NO: 944, SEQ ID NO: 815, SEQ ID NO: 1168, SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO: 694, SEQ ID NO: 1576, SEQ ID NO: 1193, SEQ ID NO: 1051, SEQ ID NO: 1212, SEQ ID NO: 806, SEQ ID NO: 1059, SEQ ID NO: 1374, SEQ ID NO: 195, SEQ ID NO: 358, SEQ ID NO: or SEQ ID NO: 1296. 1043. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1575. 1044. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1573. 1045. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1567. 1046. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1569. 1047. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1570. 1048. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1566. 1049. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1572. 1050. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1587. 1051. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1571. 1052. The composition of embodiment 1042, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1574. 1053. The composition of any one of embodiments 6-8, wherein the engineered guide RNA comprises a sequence of any one of SEQ ID NO: 1575, SEQ ID NO: 1573, SEQ ID NO: 1569, SEQ ID NO: 1574, SEQ ID NO: 1570, SEQ ID NO: 1572, SEQ ID NO: 1567, SEQ ID NO: 1587, SEQ ID NO: 1566, SEQ ID NO: 1571, SEQ ID NO: 1588, SEQ ID NO: 72, SEQ ID NO: 1586, SEQ ID NO: 1584, SEQ ID NO: 1581, SEQ ID NO: 1578, SEQ ID NO: 1585, SEQ ID NO: 1582, SEQ ID NO: 1580, SEQ ID NO: 1183, SEQ ID NO: 1568, SEQ ID NO: 1066, SEQ ID NO: 1391, SEQ ID NO: 1168, SEQ ID NO: 1293, SEQ ID NO: 1577, SEQ ID NO: 1054, SEQ ID NO: 566, SEQ ID NO: 1579, SEQ ID NO: 930, SEQ ID NO: 694, SEQ ID NO: 944, SEQ ID NO: 195, SEQ ID NO: 1583, SEQ ID NO: 815, SEQ ID NO: 1576, SEQ ID NO: 1051, SEQ ID NO: 1411, SEQ ID NO: 24, SEQ ID NO: 1163, SEQ ID NO: 935, SEQ ID NO: 680, SEQ ID NO: 1212, SEQ ID NO: 594, SEQ ID NO: 1185, SEQ ID NO: 1463, SEQ ID NO: 1058, SEQ ID NO: 810, SEQ ID NO: 392, SEQ ID NO: or SEQ ID NO: 1104. 1054. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1575. 1055. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1573. 1056. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1569. 1057. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1574. 1058. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1570. 1059. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1572. 1060. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1567. 1061. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1587. 1062. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1566. 1063. The composition of embodiment 1053, wherein the engineered guide RNA comprises the sequence of SEQ ID NO: 1571. 1064. The composition of embodiment 1, wherein the one or more structural features comprises the bulge, wherein the bulge is a symmetric bulge. 1065. The composition of embodiment 1, wherein the one or more structural features comprises the bulge, wherein the bulge is an asymmetric bulge. 1066. The composition of embodiment 1, wherein the one or more structural features comprises the internal loop, wherein the internal loop is a symmetric internal loop. 1067. The composition of embodiment 1, wherein the one or more structural features comprises the internal loop, wherein the internal loop is an asymmetric internal loop. 1068. The composition of embodiment 1, wherein the guide-target RNA scaffold further comprises a Wobble base pair. 1069. The composition of embodiment 1, wherein the one or more structural features comprises the hairpin, wherein the hairpin is a recruitment hairpin or a non-recruitment hairpin. 1070. The composition of embodiment 1, wherein the one or more structural features comprises the mismatch formed by a base in the engineered guide RNA to a G, a C, or a U in the DUX4 target RNA. 1071. The composition of embodiment 1, wherein the RNA editing entity comprises ADAR1, ADAR2, ADAR3, or any combination thereof. 1072. The composition of embodiment 1, wherein the RNA editing of one or more target adenosines comprises hyper-editing. 1073. The composition of embodiment 1072, wherein the hyper-editing comprises editing of more than one A in the polyA signal sequence of the DUX4 target RNA. 1074. The composition of embodiment 1, wherein the internal loop of the engineered guide RNA comprises any nucleotide in any positional order, wherein the nucleotide in any positional order is not complementary to their positional counterpart in the DUX 4 target RNA. 1075. The composition of any one of embodiments 1-1074, wherein the engineered guide RNA or the engineered polynucleotide encoding the engineered guide RNA is circular. 1076. The composition of any one of embodiments 1-1075, wherein the engineered guide RNA or the engineered polynucleotide encoding the engineered guide RNA comprises a U7 hairpin sequence, a SmOPT sequence, or a combination thereof and optionally wherein the U7 hairpin sequence comprises SEQ ID NO 1591 or 1593 and wherein the SmOPT sequence comprises SEQ ID NO: 1595. 1077. The composition of embodiment 1, wherein the DUX4 target RNA comprises a pre-mRNA transcript of DUX4. 1078. The composition of embodiment 1077, wherein at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence. 1079. The composition of embodiment 1078, wherein at least 80% of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence. 1080. The composition of any one of embodiments 1-1079, wherein the editing of one or more adenosines facilitates a mRNA knockdown. 1081. The composition of embodiment 1080, wherein the mRNA knockdown comprises a knockdown of DUX4 mRNA. 1082. The composition of embodiment 1080 or 1081, wherein the mRNA knockdown comprises a mRNA knockdown of a protein downstream of DUX4, wherein the protein downstream of DUX4 comprises SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2, or any combination thereof 1083. The method of any one of embodiments 1080-1082, wherein the mRNA knockdown comprises a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of a mRNA level after RNA editing as compared to a mRNA level before RNA editing. 1084. The composition of embodiment 1083, wherein the mRNA knockdown is at least 50% of the mRNA level as compared to the mRNA level before RNA editing. 1085. The composition of embodiment 1083, wherein the mRNA knockdown is at least 70% of the mRNA level as compared to the mRNA level before RNA editing. 1086. The composition of any one of embodiments 1-1085, wherein the editing of one or more adenosines facilitates a protein knockdown. 1087. The composition of embodiment 1086, wherein the protein knockdown comprises a knockdown of DUX4. 1088. The composition of embodiment 1086 or 1087, wherein the protein knockdown comprises a knockdown of a protein downstream of DUX4, wherein the protein downstream of DUX4 comprises SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2, or any combination thereof 1089. The composition of any one of embodiments 1086-1088, wherein the protein knockdown comprises a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein level after RNA editing as compared to the protein level before RNA editing. 1090. The composition of any one of embodiments 1086-1088, wherein the protein knockdown comprises a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein level in an ADAR expressing cell as compared to a cell comprising an nonfunctional ADAR gene. 1091. The composition of any one of embodiments 1086-1090, wherein the protein knockdown comprises ADAR-dependent protein knockdown. 1092. The composition of embodiment 1091, wherein the ADAR-dependent protein knockdown comprises a reduction of at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein level as compared to the protein level before RNA editing. 1093. The composition of any one of embodiments 1-1092, wherein the engineered guide RNA is an in vitro transcribed (IVT) engineered guide RNA. 1094. The composition of any one of embodiments 1-1092, comprising the engineered polynucleotide. 1095. The composition of embodiment 1094, wherein the engineered polynucleotide is comprised in or on a vector. 1096. The composition of embodiment 1095, wherein the vector is a viral vector, and wherein the engineered polynucleotide is encapsidated in the viral vector. 1097. The composition of embodiment 1096, wherein the viral vector is an adeno-associated viral (AAV) vector or a derivative thereof. 1098. The composition of embodiment 1097, wherein the AAV vector is an AAV1 serotype, an AAV2 serotype, an AAV3 serotype, an AAV4 serotype, an AAV5 serotype, an AAV6 serotype, an AAV7 serotype, an AAV8 serotype, an AAV9 serotype, an AAV10 serotype, an AAV 11 serotype, an AAV12 serotype, an AAV13 serotype, an AAV14 serotype, an AAV15 serotype, an AAV16 serotype, an AAV.rh8 serotype, an AAV.rh10 serotype, an AAV.rh20 serotype, an AAV.rh39 serotype, an AAV.Rh74 serotype, an AAV.RHM4-1 serotype, an AAV.hu37 serotype, an AAV.Anc80 serotype, an AAV.Anc80L65 serotype, an AAV.7m8 serotype, an AAV.PHP.B serotype, an AAV2.5 serotype, an AAV2tYF serotype, an AAV3B serotype, an AAV.LK03 serotype, an AAV.HSC1 serotype, an AAV.HSC2 serotype, an AAV.HSC3 serotype, an AAV.HSC4 serotype, an AAV.HSC5 serotype, an AAV.HSC6 serotype, an AAV.HSC7 serotype, an AAV.HSC8 serotype, an AAV.HSC9 serotype, an AAV.HSC10 serotype, an AAV.HSC11 serotype, an AAV.HSC12 serotype, an AAV.HSC13 serotype, an AAV.HSC14 serotype, an AAV.HSC15 serotype, an AAV.HSC16 serotype, and an AAVhu68 serotype, a derivative of any of these serotypes, or any combination thereof. 1099. The composition of embodiment 1098, wherein the AAV vector is an AAV5 serotype, an AAV6 serotype, an AAV8 serotype, or an AAV9 serotype. 1100. The composition of any one of embodiments 1097-1099, wherein the AAV vector is a recombinant AAV (rAAV) vector, a hybrid AAV vector, a chimeric AAV vector, a self-complementary AAV (scAAV) vector, or any combination thereof. 1101. The composition of embodiment 1095, wherein the vector is a non-viral vector. 1102. The composition of embodiment 1101, wherein the non-viral vector is a lipid nanoparticle (LNP), a liposome, or a polymer nanoparticle. 1103. The composition of embodiment 1094, wherein the engineered polynucleotide is a DNA polynucleotide encoding the engineered guide RNA. 1104. The composition of embodiment 1, wherein the engineered guide RNA comprises at least 80%, 85%, 90%, 92%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 2-SEQ ID NO: 1589. 1105. The composition of embodiment 1, wherein the engineered guide RNA comprises a sequence of any one of SEQ ID NO: 2-SEQ ID NO: 1589. 1106. A pharmaceutical composition comprising: a) the composition of any one of embodiments 1-1105; and b) a pharmaceutically acceptable: excipient, carrier, or diluent. 1107. A method of treating a disease or a condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of any one of embodiments 1-1105 or the pharmaceutical composition of embodiment 1106. 1108. The method of embodiment 1107, wherein the disease or condition comprises facioscapulohumeral muscular dystrophy. 1109. The method of embodiment 1108, wherein FSHD comprises Type I FSHD. 1110. The method of embodiment 1108, wherein FSHD comprises Type II FSHD. 1111. The method of any one of embodiments 1107-1110, wherein the administering comprises parenteral administration, intravenous administration, subcutaneous administration, intrathecal administration, intraperitoneal administration, intramuscular administration, intravascular administration, infusion administration, topical administration, oral administration, inhalation administration, intraduodenal administration, rectal administration, or a combination thereof. 1112. The method of embodiment 1111, comprising the administering, wherein the administration is oral administration. 1113. The method of embodiment 1111, comprising the administering, wherein the administration is in the form of an injection. 1114. The method of any one of embodiments 1107-1113, wherein the administering comprises systemic administration. 1115. A method of editing a DUX4 RNA the method comprising contacting the DUX4 RNA with any one of the compositions of embodiments 1-1105 and an RNA editing entity, thereby editing the DUX4 RNA. 1116. The method of embodiment 1115, wherein the editing comprises editing at any A position of a polyA tail of the DUX4 RNA. 1117. The method of embodiment 1116, wherein the editing comprises editing from about 44% to about 91% of any A position of the polyA tail of the DUX4 RNA as measured in an in vitro assay. 1118. The method of embodiment 1116, wherein the editing comprises editing at position 0 of the polyA tail of the DUX4 RNA. 1119. The method of embodiment 1118, wherein the editing comprises editing from about 50% to about 66% of the A at position 0 in the polyA tail of the DUX4 RNA as measured in an in vitro assay. 1120. The method of embodiment 1118 or 1119, wherein the engineered guide RNA in the composition comprises a sequence selected from the group consisting of: SEQ ID NO: 1575, SEQ ID NO: 593, SEQ ID NO: 1573, SEQ ID NO: 934, SEQ ID NO: 1569, SEQ ID NO: 1567, SEQ ID NO: 851, SEQ ID NO: 1211, SEQ ID NO: 1571, SEQ ID NO: 937, SEQ ID NO: 1574, SEQ ID NO: 1570, SEQ ID NO: 1566, SEQ ID NO: 1117, SEQ ID NO: 906, SEQ ID NO: 1572, SEQ ID NO: 1104, SEQ ID NO: 352, SEQ ID NO: 512, SEQ ID NO: 1587, SEQ ID NO: 375, SEQ ID NO: 1588, SEQ ID NO: 977, SEQ ID NO: 642, SEQ ID NO: 1236, SEQ ID NO: 1584, SEQ ID NO: 252, SEQ ID NO: 394, SEQ ID NO: 482, SEQ ID NO: 1585, SEQ ID NO: 291, SEQ ID NO: 356, SEQ ID NO: 1054, SEQ ID NO: 1581, SEQ ID NO: 1103, SEQ ID NO: 502, SEQ ID NO: 769, SEQ ID NO: 408, SEQ ID NO: 1586, SEQ ID NO: 1008, SEQ ID NO: 737, SEQ ID NO: 985, SEQ ID NO: 679, SEQ ID NO: 727, SEQ ID NO: 1578, SEQ ID NO: 365, SEQ ID NO: 1580, SEQ ID NO: 487, SEQ ID NO: 1098, and SEQ ID NO: 976. 1121. The method of embodiment 1116, wherein the editing comprises editing at position 3 of the polyA tail of the DUX4 RNA. 1122. The method of embodiment 1121, wherein the editing comprises editing from about 76% to about 91% of the A at position 3 in the polyA tail of the DUX4 RNA as measured in an in vitro assay. 1123. The method of embodiment 1121 or 1122, wherein the engineered guide RNA in the composition comprises a sequence selected from the group consisting of: SEQ ID NO: 1573, SEQ ID NO: 1588, SEQ ID NO: 1545, SEQ ID NO: 1575, SEQ ID NO: 1569, SEQ ID NO: 1584, SEQ ID NO: 1572, SEQ ID NO: 1567, SEQ ID NO: 1570, SEQ ID NO: 1587, SEQ ID NO: 1574, SEQ ID NO: 625, SEQ ID NO: 1571, SEQ ID NO: 874, SEQ ID NO: 17, SEQ ID NO: 1585, SEQ ID NO: 757, SEQ ID NO: 1581, SEQ ID NO: 1538, SEQ ID NO: 8, SEQ ID NO: 1002, SEQ ID NO: 1566, SEQ ID NO: 486, SEQ ID NO: 1552, SEQ ID NO: 505, SEQ ID NO: 635, SEQ ID NO: 606, SEQ ID NO: 884, SEQ ID NO: 1054, SEQ ID NO: 880, SEQ ID NO: 1411, SEQ ID NO: 1568, SEQ ID NO: 871, SEQ ID NO: 1580, SEQ ID NO: 1539, SEQ ID NO: 14, SEQ ID NO: 892, SEQ ID NO: 1116, SEQ ID NO: 15, SEQ ID NO: 1586, SEQ ID NO: 593, SEQ ID NO: 10, SEQ ID NO: 977, SEQ ID NO: 1578, SEQ ID NO: 1579, SEQ ID NO: 747, SEQ ID NO: 1577, 748, SEQ ID NO: 873, and SEQ ID NO: 494. 1124. The method of embodiment 1116, wherein the editing comprises editing at position 4 of the polyA tail of the DUX4 RNA. 1125. The method of embodiment 1124, wherein the editing comprises editing from about 54% to about 77% of the A at position 4 in the polyA tail of the DUX4 RNA as measured in an in vitro assay. 1126. The method of embodiment 1124 or 1125, wherein the engineered guide RNA in the composition comprises a sequence selected from the group consisting of: SEQ ID NO: 1575, SEQ ID NO: 1573, SEQ ID NO: 1567, SEQ ID NO: 1569, SEQ ID NO: 1570, SEQ ID NO: 1566, SEQ ID NO: 1572, SEQ ID NO: 1587, SEQ ID NO: 1571, SEQ ID NO: 1574, SEQ ID NO: 1584, SEQ ID NO: 1588, SEQ ID NO: 1054, SEQ ID NO: 1586, SEQ ID NO: 1585, SEQ ID NO: 1581, SEQ ID NO: 1578, SEQ ID NO: 1580, SEQ ID NO: 934, SEQ ID NO: 72, SEQ ID NO: 1582, SEQ ID NO: 1066, SEQ ID NO: 1183, SEQ ID NO: 1577, SEQ ID NO: 967, SEQ ID NO: 1568, SEQ ID NO: 930, SEQ ID NO: 566, SEQ ID NO: 1463, SEQ ID NO: 1294, SEQ ID NO: 1293, SEQ ID NO: 1391, SEQ ID NO: 1579, SEQ ID NO: 1583, SEQ ID NO: 944, SEQ ID NO: 815, SEQ ID NO: 1168, SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO: 694, SEQ ID NO: 1576, SEQ ID NO: 1193, SEQ ID NO: 1051, SEQ ID NO: 1212, SEQ ID NO: 806, SEQ ID NO: 1059, SEQ ID NO: 1374, SEQ ID NO: 195, SEQ ID NO: 358, SEQ ID NO; and SEQ ID NO: 1296. 1127. The method of embodiment 1116, wherein the editing comprises editing at position 5 of the polyA tail of the DUX4 RNA. 1128. The method of embodiment 1127, wherein the editing comprises editing from about 44% to about 70% of the A at position 4 in the polyA tail of the DUX4 RNA as measured in an in vitro assay. 1129. The method embodiment 1127 or 1128, wherein the engineered guide RNA in the composition comprises a sequence selected from the group consisting of: SEQ ID NO: 1575, SEQ ID NO: 1573, SEQ ID NO: 1569, SEQ ID NO: 1574, SEQ ID NO: 1570, SEQ ID NO: 1572, SEQ ID NO: 1567, SEQ ID NO: 1587, SEQ ID NO: 1566, SEQ ID NO: 1571, SEQ ID NO: 1588, SEQ ID NO: 72, SEQ ID NO: 1586, SEQ ID NO: 1584, SEQ ID NO: 1581, SEQ ID NO: 1578, SEQ ID NO: 1585, SEQ ID NO: 1582, SEQ ID NO: 1580, SEQ ID NO: 1183, SEQ ID NO: 1568, SEQ ID NO: 1066, SEQ ID NO: 1391, SEQ ID NO: 1168, SEQ ID NO: 1293, SEQ ID NO: 1577, SEQ ID NO: 1054, SEQ ID NO: 566, SEQ ID NO: 1579, SEQ ID NO: 930, SEQ ID NO: 694, SEQ ID NO: 944, SEQ ID NO: 195, SEQ ID NO: 1583, SEQ ID NO: 815, SEQ ID NO: 1576, SEQ ID NO: 1051, SEQ ID NO: 1411, SEQ ID NO: 24, SEQ ID NO: 1163, SEQ ID NO: 935, SEQ ID NO: 680, SEQ ID NO: 1212, SEQ ID NO: 594, SEQ ID NO: 1185, SEQ ID NO: 1463, SEQ ID NO: 1058, SEQ ID NO: 810, SEQ ID NO: 392, SEQ ID NO; and SEQ ID NO: 1104. 1130. The method of embodiment 1115, wherein the DUX4 RNA comprises a pre-mRNA transcript of DUX4. 1131. The method of embodiment 1130, wherein at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the pre-mRNA transcripts of DUX4 have at least one edit in the polyA signal sequence. 1132. The method of embodiment 1115, wherein the editing of DUX4 RNA facilitates a protein knockdown. 1133. The method of embodiment 1132, wherein the protein knockdown comprises a knockdown of DUX4. 1134. The method of embodiment 1132 or 1133, wherein the protein knockdown comprises a knockdown of a protein downstream of DUX4, wherein the protein downstream of DUX4 comprises SLC34A2, LEUTX, ZSCAN4, PRAMEF12, TRIM43, DEFB103, or MBD3L2, or any combination thereof. 1135. The composition of any one of embodiments 1132-1134, wherein the protein knockdown comprises a reduction of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the protein as compared to the protein level before RNA editing. 1136. The method of any one of embodiments 1132-1135, wherein an increased editing of the DUX4 RNA by the guide RNA is measured in an assay, wherein the increased editing comprises an increase in the protein knockdown. 1137. The composition of any one of embodiments 1-1105 or the pharmaceutical composition of embodiment 1106 for use as a medicament. 1138. The composition of any one of embodiments 1-1105 or the pharmaceutical composition of embodiment 1106 for use in the treatment of facioscapulohumeral muscular dystrophy (FSHD). 1139. The composition of embodiment 1138, wherein FSHD comprises Type I FSHD. 1140. The composition of embodiment 1138, wherein FSHD comprises Type II FSHD.

EXAMPLES

The following illustrative examples are representative of embodiments of the stimulation, systems, and methods described herein and are not meant to be limiting in any way.

Example 1
Engineered Guide RNAs for Editing DUX4 TIS

This example describes engineered guide RNAs for editing DUX4 RNA to knockdown expression of the DUX4 protein. A schematic of the DUX4 target is shown in FIG. 1, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. Engineered guide RNAs of the present disclosure are designed to target the single translation initiation site (TIS) of DUX4 RNA and facilitate ADAR-mediated RNA editing of AUG (the TIS) to GUG, thus, inhibiting DUX4 translation. Editing results in knockdown of the DUX4 protein, given that there are no other nearby methionine residues available for alternative translation initiation. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit the DUX4 TIS, thereby normalizing expression of DUX4 target genes. Upon administration to a subject having facioscapulohumeral muscular dystrophy (FSHD), the engineered guide RNAs are therapeutically effective and restore proper muscle function.

Example 2

Engineered Guide RNAs for Editing DUX4 polyA Signal Site

This example describes engineered guide RNAs for editing DUX4 (DUX4-FL) RNA to knockdown expression of the corresponding DUX4 protein. A schematic of the DUX4 target is shown in FIG. 1, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. Engineered guide RNAs of the present disclosure are designed to target one or more adenosines in the single polyA signal sequence (ATTAAA) of DUX4-FL RNA and facilitate ADAR-mediated RNA editing of said one or more adenosines, thus, leading to disruption of RNA processing and inducement of degradation of the mRNA. This in turn leads to knockdown of the toxic DUX4-FL protein. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit the DUX4 polyA signal sequence, thereby normalizing expression of DUX4 target genes. Upon administration to a subject having facioscapulohumeral muscular dystrophy (FSHD), the engineered guide RNAs are therapeutically effective and restore proper muscle function.

Example 3

Engineered Guide RNAs for Editing DMPK polyA Signal Site

This example describes engineered guide RNAs for editing DMPK RNA to knockdown expression of myotonic dystrophy protein kinase. A schematic of the DMPK target is shown in FIG. 2, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. Engineered guide RNAs of the present disclosure are designed to target one or more adenosines in the polyA signal region of DMPK RNA and facilitate ADAR-mediated RNA editing of said one or more adenosines, thus, leading to disruption of RNA processing and inducement of degradation of the toxic mRNA. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit the DMPK polyA signal region. Upon administration to a subject having myotonic dystrophy (DM1), the engineered guide RNAs are therapeutically effective and prevent myotonia and muscle wasting.

Example 4
Engineered Guide RNAs for Editing DMPK TIS

This example describes engineered guide RNAs for editing DMPK RNA to knockdown expression of myotonic dystrophy protein kinase. A schematic of the DMPK target is shown in FIG. 2, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. Engineered guide RNAs of the present disclosure are designed to target the single translation initiation site (TIS) of DMPK RNA and facilitate ADAR-mediated RNA editing of AUG (the TIS) to GUG, thus, inhibiting DMPK translation. Editing results in knockdown of myotonic dystrophy protein kinase, given that there are no other nearby methionine residues available for alternative translation initiation. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit the DMPK TIS. Upon administration to a subject having myotonic dystrophy (DM1), the engineered guide RNAs are therapeutically effective and prevent myotonia and muscle wasting.

Example 5
Engineered Guide RNAs for Editing PMP22 TIS

This example describes engineered guide RNAs for editing PMP22 RNA to knockdown expression of peripheral myelin protein-22 (PMP22). A schematic of the PMP22 target is shown in FIG. 3, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. Engineered guide RNAs of the present disclosure are designed to target the single translation initiation site (TIS) of PMP22 RNA and facilitate ADAR-mediated RNA editing of AUG (the TIS) to GUG, thus, inhibiting PMP22 translation. Editing results in knockdown of the PMP22 protein, given that there are no other nearby methionine residues available for alternative translation initiation. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit the PMP22 TIS. Upon administration to a subject having Charcot-Marie-Tooth Syndrome (CMT1A), the engineered guide RNAs are therapeutically effective and restore proper peripheral nerve myelination and conductance and improve muscle strength and sensory function.

Example 6

Engineered Guide RNAs for Editing PMP22 polyA Signal Site

This example describes engineered guide RNAs for editing PMP22 RNA to knockdown expression of peripheral myelin protein-22 (PMP22). A schematic of the PMP22 target is shown in FIG. 3, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. One or more different engineered guide RNAs of the present disclosure are designed to target adenosines in one or more of the three alternative polyA signal sites of PMP22 RNA and facilitate ADAR-mediated RNA editing of said adenosines in said one or more of the three alternative polyA signal sites. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit one or more of the three alternative polyA signal sites. Upon administration to a subject having Charcot-Marie-Tooth Syndrome (CMT1A), the engineered guide RNAs are therapeutically effective and restore proper peripheral nerve myelination and conductance and improve muscle strength and sensory function.

Example 7
Engineered Guide RNAs for Editing SOD1 TIS

This example describes engineered guide RNAs for editing SOD1 RNA to knockdown expression of the superoxide dismutase enzyme. A schematic of the SOD1 target is shown in FIG. 4, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. Engineered guide RNAs of the present disclosure are designed to target the single translation initiation site (TIS) of SOD1 RNA and facilitate ADAR-mediated RNA editing of AUG (the TIS) to GUG, thus, inhibiting SOD1 translation and toxic protein function. Editing results in knockdown of the superoxide dismutase enzyme, given that there are no other nearby methionine residues available for alternative translation initiation. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit the SOD1 TIS. Upon administration to a subject having amyotrophic lateral sclerosis (ALS), the engineered guide RNAs are therapeutically effective and prevent motor neuron degeneration and disease progression.

Example 8

Engineered Guide RNAs for Editing SOD1 polyA Signal Site

This example describes engineered guide RNAs for editing SOD1 RNA to knockdown expression of the superoxide dismutase enzyme. A schematic of the SOD1 target is shown in FIG. 4, highlighting sites that can be targeted by engineered guide RNAs of the present disclosure. One or more different engineered guide RNAs of the present disclosure are designed to target adenosines in one or more of the three alternative polyA signal sites of SOD1 RNA and facilitate ADAR-mediated RNA editing of said adenosines in said one or more of the three alternative polyA signal sites. Upon administration to of the engineered guide RNAs, in vitro or in vivo, the engineered guide RNAs edit one or more of the three alternative polyA signal sites. Upon administration to a subject having amyotrophic lateral sclerosis (ALS), the engineered guide RNAs are therapeutically effective and prevent motor neuron degeneration and disease progression.

Example 9
Engineered Guide RNA Compositions Targeting DUX4

This example describes engineered guide RNAs that target the polyadenylation (polyA) signal site (ATTAAA) in the “pLAM” region of DUX4 mRNA. One or more of the three terminal As in the polyA signal site sequence (ATTAAA) was targeted for editing using the engineered guide RNA sequences of TABLE 1. The results from the DUX4 polyA signal site editing (percent editing of an indicated A) are shown in TABLE 2. TABLE 2 shows the percent editing of As in ATTAAA of DUX4 mRNA by ADAR1 (A1), ADAR2 (A2), or ADAR1 and ADAR2 (A1+2) with the guide RNAs described in TABLE 1. Position 0 (the first A of ATTAAA) is indicated as “P0”, position 3 (the third A of ATTAAA) is indicated as “P3”, position 4 (the fourth A of ATTAAA) is indicated as “P4”, position 5 (the fifth A of ATTAAA) is indicated as “P5”, and editing at any of the locations is indicated as “any” in TABLE 2. Self-annealing RNA structures, which comprised (i) the engineered guide RNAs shown in TABLE 1 and (ii) the RNA sequences of the DUX4 region targeted by the engineered guide RNAs, were contacted with an RNA editing entity (e.g., a recombinant ADAR1 and/or ADAR2) for 30 minutes under conditions that allowed for editing. The regions targeted by the engineered guide RNAs were subsequently assessed for editing using next generation sequencing (NGS). Engineered guide RNAs that displayed favorable on-target editing of DUX4 for ADAR1 and/or ADAR2 are shown in TABLE 1. All polynucleotide sequences encoding for the engineered guide RNAs of TABLE 1, are also encompassed herein, which are represented by each of the sequences shown in TABLE 1, with a T substituted for each U. For each sequence, the structural features formed in the double stranded RNA substrate upon hybridization of the guide RNA to the target DUX4 RNA, are shown in the second column of TABLE 1. For reference, each structural feature formed within a guide-target RNA scaffold (target RNA sequence hybridized to an engineered guide RNA) is annotated as follows:

- a. the position of the structural feature with respect to the target A (position 0) of the target RNA sequence, with a negative value indicating upstream (5′) of the target A and a positive value indicating downstream (3′) of the target A;
- b. the number of bases in the target RNA sequence and the number of bases in the engineered guide RNA that together form the structural feature—for example, 6/6 indicates that six contiguous bases from the target RNA sequence and six contiguous bases from the engineered guide RNA form the structural feature;
- c. the name of the structural feature (e.g., symmetric bulge, symmetric internal loop, asymmetric bulge, asymmetric internal loop, mismatch, or wobble base pair), and
- d. the sequences of bases on the target RNA side and the engineered guide RNA side that participate in forming the structural feature.

For example, with reference to SEQ ID NO: 7, “20_6-6_internal_loop-symmetric_UGGAUC-UACAUU” is read as a structural feature formed in a guide-target RNA scaffold (target DUX4 RNA sequence hybridized to an engineered guide RNA of SEQ ID NO: 7), where

- a. the structural feature starts 20 nucleotides downstream (3′) (the +20 position) from the target A (0 position) of the target RNA sequence
- b. six contiguous bases from the target RNA sequence and six contiguous bases from the engineered guide RNA form the structural feature
- c. the structural feature is an internal symmetric loop
- d. a sequence of UGGAUC from the target RNA side and a sequence of UACAUU from the engineered guide RNA side participate in forming the internal symmetric loop.

For reference, FIG. 5 can be used as an aid to visualize the structural features and the nomenclature disclosed herein. FIG. 6 is a plot showing, on the x-axis, the sequence similarity of the DUX4-targeting engineered guide RNA sequences of the present disclosure to a canonical guide RNA design and, on the y-axis, the edited fraction by an ADAR2 enzyme. These data highlight the diverse sequence space represented by the DUX4-targeting engineered guide RNA sequences of the present disclosure, which have a range of different structural features that drive sequence diversity, and which exhibit high on-target editing efficiency.

TABLE 1

Engineered Guide RNAs Targeting DUX4

SEQ

ID
Structural
Engineered Guide

NO
Features
RNA sequence

2
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUCCACAGGGAGGGGGCAUUUUAAC

AUAUCUCUGAACUAAUCAUC

3
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUCCACAGGGAGGGGGCAUUUCAAU

AUAUCUCUGAACUAAUCAUC

4
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUCCACAGGGAGGGGGCAUUCUAAU

AUAUCUCUGAACUAAUCAUC

5
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUCCACAGGGAGGGGGCAUCUUAAU

AUAUCUCUGAACUAAUCAUC

6

GAUAUUGUGACAUAUCUCUGCACUCAU

CACACAAAAGAUGCAAAUCUUCUAUAG

GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

7
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

20_6-6_internal_
UACAUUCAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGGAUC-UACAUU

8
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

20_6-6_internal_
ACAGGUCAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGGAUC-ACAGGU

9
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

20_6-6_internal_
CACAAUCAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGGAUC-CACAAU

10
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAG

20_6-6_internal_
UUAGAUCAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGGAUC-UUAGAU

11
20_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UGGAUC-AAAAUU
AAAAUUCAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

12
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAA

21_6-6_internal_
ACAUAACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GGAUCC-AACAUA

13
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAU

21_6-6_internal_
AAGUAACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GGAUCC-UAAGUA

14
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUAU

21_6-6_internal_
CGCGGACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GGAUCC-UCGCGG

15
21_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

GGAUCC-CCCCAA
CCCAAACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

16
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUUG

22_6-6_internal_
UCGACACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GAUCCU-UGUCGA

17
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUCC

22_6-6_internal_
CCGACACAGGGAGGGGGCAUUUCAAUA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

GAUCCU-CCCCGA

18
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUUU

22_6-6_internal_
CUAACACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GAUCCU-UUCUAA

19
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAUCA

22_6-6_internal_
CCGACACAGGGAGGGGGCAUCUUAAUA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

GAUCCU-CACCGA

20
22_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

GAUCCU-UACUAA
CUAACACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

21
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAGAU

23_6-6_internal_
CUCCCACAGGGAGGGGGCAUUUUAACA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

AUCCUA-GAUCUC

22
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAGUC

23_6-6_internal_
ACGCCACAGGGAGGGGGCAUUUCAAUA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

AUCCUA-GUCACG

23
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUAAUA

23_6-6_internal_
UCCCCACAGGGAGGGGGCAUUCUAAUA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

AUCCUA-AUAUCC

24
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUACGU

23_6-6_internal_
CCGCCACAGGGAGGGGGCAUCUUAAUA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

AUCCUA-CGUCCG

25
23_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGAA

AUCCUA-GAAUCG
UCGCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

26
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUUACA

24_6-6_internal_
GUUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UCCUAU-UACAGU

27
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUUCUA

24_6-6_internal_
CUUCCACAGGGAGGGGGCAUUUCAAUA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

UCCUAU-UCUACU

28
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUUCGC

24_6-6_internal_
GUUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UCCUAU-UCGCGU

29
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCUCCGU

24_6-6_internal_
AUUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UCCUAU-CCGUAU

30
24_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGUC

UCCUAU-UGUCUC
UCUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

31
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCACCGA

25_6-6_internal_
CAUCCACAGGGAGGGGGCAUUUUAACA

loop-symmetric_
UAUCUCUGAACUAAUCAUC

CCUAUA-ACCGAC

32
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCCCAUU

25_6-6_internal_
UAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CCUAUA-CCAUUU

33
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCCCUUU

25_6-6_internal_
AAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CCUAUA-CCUUUA

34
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUCAUCGU

25_6-6_internal_
UAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CCUAUA-AUCGUU

35
25_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAAGAA

CCUAUA-AAGAAA
AAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

36
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUAAUGAC

26_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CUAUAG-AAUGAC

37
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUGGGCCA

26_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CUAUAG-GGGCCA

38
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUAGUGUC

26_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CUAUAG-AGUGUC

39
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUUAGCUUU

26_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CUAUAG-AGCUUU

40
26_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGAAU

CUAUAG-GGAAUU
UGAUCCACAGGGAGGGGGCAUUUUAA

UAUAUCUCUGAACUAAUCAUC

41
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUCAGUCUG

27_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UAUAGA-CAGUCU

42
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUAACCAUG

27_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UAUAGA-AACCAU

43
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUCCACCUG

27_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UAUAGA-CCACCU

44
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCUGUGCACG

27_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UAUAGA-GUGCAC

45
27_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGACAUCG

UAUAGA-GACAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

46
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCCAGUCAAG

28_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUAGAA-CAGUCA

47
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCACUCCGAG

28_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUAGAA-ACUCCG

48
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCCGAAACAG

28_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUAGAA-CGAAAC

49
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUCAUACGAAG

28_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUAGAA-AUACGA

50
28_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCGGGGAG

AUAGAA-CCGGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

51
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUAUUGACUA

29_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUUAA

loop-symmetric_
CAUAUCUCUGAACUAAUCAUC

UAGAAG-AUUGAC

52
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUGACCCCUAG

29_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UAGAAG-GACCCC

53
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUGCGUGCUAG

29_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UAGAAG-GCGUGC

54
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAUGAGGACUA

29_6-6_internal_
GGAUCCACAGGGAGGGGGCAUCUUAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

UAGAAG-GAGGAC

55
29_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGGAAUUA

UAGAAG-GGGAAU
GGAUCCACAGGGAGGGGGCAUUUUAA

UAUAUCUCUGAACUAAUCAUC

56
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAAGAGAGAUA

30_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUUAA

loop-symmetric_
CAUAUCUCUGAACUAAUCAUC

AGAAGA-AGAGAG

57
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAACGCACGAUAG

30_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AGAAGA-CGCACG

58
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAACCAGAGAUAG

30_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AGAAGA-CCAGAG

59
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAAAAGGCGAAUA

30_6-6_internal_
GGAUCCACAGGGAGGGGGCAUCUUAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

AGAAGA-AGGCGA

60
30_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGCAAGAAUA

AGAAGA-GCAAGA
GGAUCCACAGGGAGGGGGCAUUUUAA

UAUAUCUCUGAACUAAUCAUC

61
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAACCCCGAUAUAG

31_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GAAGAU-CCCCGA

62
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAACUAAAAUAUA

31_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUCAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

GAAGAU-CUAAAA

63
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAACGUGGGUAUA

31_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUCUAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

GAAGAU-CGUGGG

64
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAACUGGGAUAUA

31_6-6_internal_
GGAUCCACAGGGAGGGGGCAUCUUAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

GAAGAU-CUGGGA

65
31_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGGAGAUAUA

GAAGAU-UGGAGA
GGAUCCACAGGGAGGGGGCAUUUUAA

UAUAUCUCUGAACUAAUCAUC

66
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAUCCGGACUAUAG

32_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AAGAUU-UCCGGA

67
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCAUCCUGGCUAUAG

32_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AAGAUU-UCCUGG

68
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCACCUAGACUAUAG

32_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AAGAUU-CCUAGA

69
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCACCCGGACUAUAG

32_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AAGAUU-CCCGGA

70
32_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUGAGGCUAUAG

AAGAUU-CUGAGG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

71
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCUUGAGAUCUAUA

33_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUUAA

loop-symmetric_
CAUAUCUCUGAACUAAUCAUC

AGAUUU-UUGAGA

72
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCUUGGGAUCUAUA

33_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUCAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

AGAUUU-UUGGGA

73
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCUUUGCGUCUAUAG

33_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AGAUUU-UUUGCG

74
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGCCUGCACUCUAUAG

33_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AGAUUU-CUGCAC

75
33_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCGCGGGUCUAUAG

AGAUUU-CGCGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

76
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGGUUUAAUUCUAUA

34_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUCAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

GAUUUG-GUUUAA

77
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGGCUGGGUUCUAUA

34_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUCUAA

loop-symmetric_
UAUAUCUCUGAACUAAUCAUC

GAUUUG-GCUGGG

78
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUGACUCCGUUCUAUAG

34_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GAUUUG-ACUCCG

79
34_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUACAUUCUAUA

GAUUUG-GUUACA
GGAUCCACAGGGAGGGGGCAUUUUAA

UAUAUCUCUGAACUAAUCAUC

80
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUCUGUCACUUCUAUAG

35_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUUUGC-CUGUCA

81
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUCUUGAGCUUCUAUAG

35_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUUUGC-CUUGAG

82
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUCUUAGGCUUCUAUAG

35_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUUUGC-CUUAGG

83
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAUAAGUGCCUUCUAUAG

35_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUUUGC-AAGUGC

84
35_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUCCACUUCUAUAG

AUUUGC-CUUCCA
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

85
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGACAACUUUCUUCUAUAG

36_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUGCA-CAACUU

86
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGACCACUCUCUUCUAUAG

36_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUGCA-CCACUC

87
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGAACGGUUUCUUCUAUAG

36_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUGCA-ACGGUU

88
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGACACCUCUCUUCUAUAG

36_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUGCA-CACCUC

89
36_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACUAGUUUCUUCUAUAG

UUUGCA-CUAGUU
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

90
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGCGAUCCAUCUUCUAUAG

37_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUGCAU-CGAUCC

91
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGCACGUCAUCUUCUAUAG

37_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUGCAU-CACGUC

92
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGCUAGUUAUCUUCUAUAG

37_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUGCAU-CUAGUU

93
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAGCGUUUUAUCUUCUAUAG

37_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUGCAU-CGUUUU

94
37_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCUGAUAUCUUCUAUAG

UUGCAU-UCUGAU
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

95
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAACUUAUUAAUCUUCUAUAG

38_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGCAUC-CUUAUU

96
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAUUUAUCAAUCUUCUAUAG

38_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGCAUC-UUUAUC

97
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAAUUAAACAAUCUUCUAUAG

38_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UGCAUC-UUAAAC

98
38_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUACGUAAUCUUCUAUAG

UGCAUC-UUACGU
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

99
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAUCUAUAAAAUCUUCUAUAG

39_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GCAUCU-UCUAUA

100
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAUACGGAAAAUCUUCUAUAG

39_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GCAUCU-UACGGA

101
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAACUCCAGAAAUCUUCUAUAG

39_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GCAUCU-CUCCAG

102
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAAUCAACAAAAUCUUCUAUAG

39_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

GCAUCU-UCAACA

103
39_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACAUACGAAAUCUUCUAUAG

GCAUCU-CAUACG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

104
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAUAUCGUCAAAUCUUCUAUAG

40_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CAUCUU-UAUCGU

105
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAUCCGCACAAAUCUUCUAUAG

40_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CAUCUU-UCCGCA

106
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAACUUGACCAAAUCUUCUAUAG

40_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CAUCUU-CUUGAC

107
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAAUCUUUCCAAAUCUUCUAUAG

40_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CAUCUU-UCUUUC

108
40_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGCGACCAAAUCUUCUAUAG

CAUCUU-CGCGAC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

109
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAUCUAUGGCAAAUCUUCUAUAG

41_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUCUUU-UCUAUG

110
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACACGCGCCGCAAAUCUUCUAUAG

41_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUCUUU-CGCGCC

111
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAUGUAUCGCAAAUCUUCUAUAG

41_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUCUUU-UGUAUC

112
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACAUUGCUCGCAAAUCUUCUAUAG

41_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

AUCUUU-UUGCUC

113
41_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCGCCCGCAAAUCUUCUAUAG

AUCUUU-CCGCCC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

114
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACUUCUUCUGCAAAUCUUCUAUAG

42_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UCUUUU-UUCUUC

115
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACCUGCUCUGCAAAUCUUCUAUAG

42_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UCUUUU-CUGCUC

116
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACACCUUGUUUGCAAAUCUUCUAUAG

42_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UCUUUU-CUUGUU

117
42_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUAUAUUGCAAAUCUUCUAUAG

UCUUUU-CUAUAU
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

118
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACAGUUGUAAUGCAAAUCUUCUAUA

43_6-6_internal_
GGAUCCACAGGGAGGGGGCAUUUUAA

loop-symmetric_
CAUAUCUCUGAACUAAUCAUC

CUUUUG-GUUGUA

119
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACAACCUGAAUGCAAAUCUUCUAUAG

43_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CUUUUG-ACCUGA

120
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACAGCUGUCAUGCAAAUCUUCUAUAG

43_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

CUUUUG-GCUGUC

121
43_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGACCAAUGCAAAUCUUCUAUAG

CUUUUG-AGACCA
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

122
0_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACUACCUCGAUGCAAAUCUUCUAUAG

44_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUUAAC

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUUGU-UACCUC

123
3_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACCUUUCCGAUGCAAAUCUUCUAUAG

44_6-6_internal_
GAUCCACAGGGAGGGGGCAUUUCAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUUGU-CUUUCC

124
4_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACUUGCCUGAUGCAAAUCUUCUAUAG

44_6-6_internal_
GAUCCACAGGGAGGGGGCAUUCUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUUGU-UUGCCU

125
5_1-1_mismatch_
GAUAUUGUGACAUAUCUCUGCACUCAU

A-C
CACUGUUUCGAUGCAAAUCUUCUAUAG

44_6-6_internal_
GAUCCACAGGGAGGGGGCAUCUUAAU

loop-symmetric_
AUAUCUCUGAACUAAUCAUC

UUUUGU-UGUUUC

126
44_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUGCCGAUGCAAAUCUUCUAUAG

UUUUGU-CUUGCC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAACUAAUCAUC

127
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-AAACGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAAAACGAAUC

A-C

128
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-GAAGAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGAAGAGAUC

A-C

129
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-GCACGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGCACGAAUC

A-C

130
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-AGAUAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAAGAUAAAUC

A-C

131
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-ACGCCA
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAAACGCCAAUC

132
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-AAACCG
CAGGAUCAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAAAACCGAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CAGGAU

133
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-AGCGGG
CCUAAUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAGCGGGAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CCUAAU

134
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-GCCUAA
CACAGUCAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGCCUAAAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CACAGU

135
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-GCCAUA
UUAAAUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGCCAUAAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UUAAAU

136
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAUUAG-GGCCAA
CCGUGUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCUCUGAAGGCCAAAUC

loop-symmetric_

UGGAUC-CCGUGU

137
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

GAUUAG-AGAUAG
ACCGAACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAAGAUAGAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UACCGA

138
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

GAUUAG-AUUUAG
ACGCAACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAUUUAGAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CACGCA

139
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

GAUUAG-GGGGCA
AAGCAACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGGGGCAAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-AAAGCA

140
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

GAUUAG-GGGUAA
ACGAGACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUCUCUGAAGGGUAAAUC

loop-symmetric_

GGAUCC-AACGAG

141
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

GAUUAG-GGAAAA
UCAACACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGGAAAAAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCUCAA

142
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCG

GAUUAG-GGUGGG
CUGGCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGGUGGGAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CGCUGG

143
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

GAUUAG-GGCACA
AGCACACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGGCACAAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCAGCA

144
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCU

GAUUAG-AUCGAA
UGUACACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAAUCGAAAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CUUGUA

145
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

GAUUAG-GAUAGA
AGAACACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCUCUGAAGAUAGAAUC

loop-symmetric_

GAUCCU-CCAGAA

146
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGAA

GAUUAG-AGGGGG
AGCCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUGAAAGGGGGAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GAAAGC

147
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUC

GAUUAG-GCACGG
CUGCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCUGAAGCACGGAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CUCCUG

148
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACCU

GAUUAG-ACCGUA
AACCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCUGAAACCGUAAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CCUAAC

149
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUC

GAUUAG-AAGCAG
AUCCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCUGAAAAGCAGAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AUCAUC

150
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGCG

GAUUAG-GAGUGG
AAACCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUAUCUCUGAAGAGUGGAUC

loop-symmetric_

AUCCUA-GCGAAA

151
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUCUA

GAUUAG-AUCUGG
CUUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUGAAAUCUGGAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UCUACU

152
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGCC

GAUUAG-GGUACA
UUUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGGUACAAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGCCUU

153
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUACC

GAUUAG-GGAGCG
AUUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGGAGCGAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UACCAU

154
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUCAC

GAUUAG-GGCCGG
CUUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCUGAAGGCCGGAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UCACCU

155
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUCAC

GAUUAG-GGCAGA
CCUCCACAGGGAGGGGGCAUUUUAAUA

24_6-6_internal_
UAUCUCUGAAGGCAGAAUC

loop-symmetric_

UCCUAU-UCACCC

156
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGAAAC

GAUUAG-GACAGA
CAUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUGAAGACAGAAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GAAACC

157
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACAAA

GAUUAG-AGCGAG
UAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAGCGAGAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACAAAU

158
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCCCCU

GAUUAG-GGGUGG
UAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGGGUGGAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CCCCUU

159
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACCCC

GAUUAG-GACGCG
UAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGACGCGAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACCCCU

160
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGCACC

GAUUAG-GAGCCG
AAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUCUCUGAAGAGCCGAUC

loop-symmetric_

CCUAUA-GCACCA

161
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAUCGAC

GAUUAG-ACAUGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAACAUGAAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AUCGAC

162
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCCCUU

GAUUAG-ACUCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAACUCGAAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCCCUU

163
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCUCGU

GAUUAG-AGCAAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAGCAAGAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCUCGU

164
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGUGA

GAUUAG-GCCAGA
AGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAAGCCAGAAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGUGAA

165
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCGGUC

GAUUAG-GACCGG
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCUCUGAAGACCGGAUC

loop-symmetric_

CUAUAG-GCGGUC

166
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGACCUCG

GAUUAG-AUCUGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAUCUGGAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GACCUC

167
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGAUUCUG

GAUUAG-GGUUAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGGUUAAAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GAUUCU

168
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGCCUUUG

GAUUAG-AGGCCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAAGGCCGAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GCCUUU

169
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGCCUCG

GAUUAG-GCGUGA
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCUCUGAAGCGUGAAUC

loop-symmetric_

UAUAGA-GGCCUC

170
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGUAGUAA

GAUUAG-GAAUAG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAAGAAUAGAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GUAGUA

171
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGACACGAG

GAUUAG-GCAUGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGCAUGGAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GACACG

172
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGGCGCAG

GAUUAG-GAACGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAGAACGAAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GGGCGC

173
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCACCACGAG

GAUUAG-GGCAAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGGCAAAAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-ACCACG

174
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGUGAGCAG

GAUUAG-AACGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUCUCUGAAAACGGGAUC

loop-symmetric_

AUAGAA-GUGAGC

175
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCAGGUUA

GAUUAG-GCCUCG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAAGCCUCGAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCAGGU

176
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGCGUCUAG

GAUUAG-GGGACA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGGGACAAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AGCGUC

177
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGCACCUAG

GAUUAG-ACUCCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAACUCCAAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AGCACC

178
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAGAUUUA

GAUUAG-GGAGCA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAAGGAGCAAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAGAUU

179
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGACAGCUAG

GAUUAG-GACCCG
GAUCCACAGGGAGGGGGCAUUUUAAU

29_6-6_internal_
AUAUCUCUGAAGACCCGAUC

loop-symmetric_

UAGAAG-GACAGC

180
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGAGGCAUA

GAUUAG-AACCCG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAAAACCCGAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGAGGC

181
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGUAUGGAUA

GAUUAG-GCCUGG
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGAAGCCUGGAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GUAUGG

182
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGAGCGAUA

GAUUAG-AUUCGG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGAAAUUCGGAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGAGCG

183
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGUAAGAUA

GAUUAG-AUUCGG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAAAUUCGGAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGUAAG

184
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAACCAAAUAG

GAUUAG-AGGGCG
GAUCCACAGGGAGGGGGCAUUUUAAU

30_6-6_internal_
AUAUCUCUGAAAGGGCGAUC

loop-symmetric_

AGAAGA-AACCAA

185
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUAAAUAUAUA

GAUUAG-GGUUGG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAAGGUUGGAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UAAAUA

186
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAUGAAUAUA

GAUUAG-GGCGAG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAAGGCGAGAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAUGAA

187
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCAAGACUAUAG

GAUUAG-GCCGCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGCCGCGAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCAAGA

188
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACAGGACCUAUAG

GAUUAG-GCCUAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGCCUAAAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CAGGAC

189
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCUAGACUAUAG

GAUUAG-AAUACA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAAUACAAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCUAGA

190
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACAAUAACUAUAG

GAUUAG-ACCCGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAACCCGAAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CAAUAA

191
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUGAUACUAUAG

GAUUAG-GCAUAG
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAUCUCUGAAGCAUAGAUC

loop-symmetric_

AAGAUU-CUGAUA

192
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUAACGCUCUAUAG

GAUUAG-GCCGAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGCCGAAAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UAACGC

193
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUUGGCUCUAUAG

GAUUAG-GCGCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGCGCGAAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUUGGC

194
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCGCCCUCUAUAG

GAUUAG-AGUAAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAGUAAAAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCGCCC

195
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCGGGAUCUAUAG

GAUUAG-GCCCGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGCCCGGAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCGGGA

196
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCCUACUCUAUAG

GAUUAG-GACAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCUCUGAAGACAAAAUC

loop-symmetric_

AGAUUU-CCCUAC

197
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGUCGAUUCUAUA

GAUUAG-GCCACA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAAGCCACAAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AGUCGA

198
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGGGAGUUCUAUA

GAUUAG-ACUCCA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGAAACUCCAAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AGGGAG

199
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAUACAAUUCUAUA

GAUUAG-GCCGCA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGAAGCCGCAAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AUACAA

200
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCUCCGUUCUAUAG

GAUUAG-ACAAAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAACAAAAAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCUCCG

201
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUGCGUUCUAUA

GAUUAG-AGGUAA
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUAUCUCUGAAAGGUAAAUC

loop-symmetric_

GAUUUG-AAUGCG

202
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUGUCGCUUCUAUAG

GAUUAG-AUGUAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAAUGUAGAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUGUCG

203
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUACCGACUUCUAUAG

GAUUAG-AACCCA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAACCCAAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UACCGA

204
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAACUAGCUUCUAUAG

GAUUAG-AGUGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAGUGCAAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AACUAG

205
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAACCGACUUCUAUAG

GAUUAG-GGGAGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGGGAGGAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AACCGA

206
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUACGCCCUUCUAUAG

GAUUAG-AGCGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUAUCUCUGAAAGCGAGAUC

loop-symmetric_

AUUUGC-UACGCC

207
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAUUUCCUCUUCUAUAG

GAUUAG-GGCGAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGGCGAAAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AUUUCC

208
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACUACUUCUUCUAUAG

GAUUAG-AUUUAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAUUUAAAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-ACUACU

209
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGGAGCUUCUUCUAUAG

GAUUAG-AAGGGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAAGGGGAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GGAGCU

210
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCAUAUUCUUCUAUAG

GAUUAG-AAUAGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAAAUAGGAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCAUAU

211
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAUUCCUUCUUCUAUAG

GAUUAG-GAUUAG
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AUAUCUCUGAAGAUUAGAUC

loop-symmetric_

UUUGCA-AUUCCU

212
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUUAAUAUCUUCUAUAG

GAUUAG-AAUUGG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAAAUUGGAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUUAAU

213
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCUAUUAUCUUCUAUAG

GAUUAG-GGAGGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGGAGGGAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCUAUU

214
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAAUUUAUCUUCUAUAG

GAUUAG-GCCCGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGCCCGAAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CAAUUU

215
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUACUCUAUCUUCUAUAG

GAUUAG-GGUGCG
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUCUCUGAAGGUGCGAUC

loop-symmetric_

UUGCAU-UACUCU

216
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUCAGUAAUCUUCUAUAG

GAUUAG-GGUGGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGGUGGAAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUCAGU

217
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUUUUUAAUCUUCUAUA

GAUUAG-GGGCAG
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGAAGGGCAGAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UUUUUU

218
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAACAGUAAUCUUCUAUAG

GAUUAG-ACGGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAACGGGAAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AACAGU

219
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAACGAACAAUCUUCUAUAG

GAUUAG-GGACGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGGACGGAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-ACGAAC

220
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUCUUUAAUCUUCUAUAG

GAUUAG-GAUGCG
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCUCUGAAGAUGCGAUC

loop-symmetric_

UGCAUC-AUCUUU

221
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUCUAGAAAUCUUCUAUAG

GAUUAG-GCGGAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGCGGAGAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUCUAG

222
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUGACAAAAUCUUCUAUAG

GAUUAG-AUGCGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAUGCGGAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUGACA

223
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUCGUAAAAUCUUCUAUAG

GAUUAG-GACAAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGACAAAAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUCGUA

224
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACAUUAACAAAUCUUCUAUAG

GAUUAG-AUCCGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAAUCCGAAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CAUUAA

225
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCCCCCCAAAUCUUCUAUAG

GAUUAG-GCUCAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGCUCAAAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCCCCC

226
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUACGCCCAAAUCUUCUAUAG

GAUUAG-AGCAAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAGCAAAAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UACGCC

227
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACUACAUCAAAUCUUCUAUAG

GAUUAG-AAGUGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAAAGUGAAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CUACAU

228
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCGCGCCAAAUCUUCUAUAG

GAUUAG-GCCAUA
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAUCUCUGAAGCCAUAAUC

loop-symmetric_

CAUCUU-CCGCGC

229
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCCGCGGCAAAUCUUCUAUAG

GAUUAG-GCACGG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGCACGGAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCCGCG

230
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACGCUUAGCAAAUCUUCUAUAG

GAUUAG-ACGUAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAACGUAGAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CGCUUA

231
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCCCAAGCAAAUCUUCUAUAG

GAUUAG-AGUUAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAGUUAGAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCCCAA

232
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUCCAAGCAAAUCUUCUAUAG

GAUUAG-ACACGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAACACGGAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUCCAA

233
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCAUUAGCAAAUCUUCUAUAG

GAUUAG-AUUGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCUCUGAAAUUGGGAUC

loop-symmetric_

AUCUUU-UCAUUA

234
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCGUAUCUGCAAAUCUUCUAUAG

GAUUAG-GGGACG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGGGACGAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CGUAUC

235
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUGGCCUGCAAAUCUUCUAUAG

GAUUAG-AGGCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAAGGCGAAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUGGCC

236
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUAACGUUGCAAAUCUUCUAUAG

GAUUAG-ACGCAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAACGCAGAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UAACGU

237
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGUGCUUGCAAAUCUUCUAUAG

GAUUAG-GCCAGA
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCUCUGAAGCCAGAAUC

loop-symmetric_

UCUUUU-UGUGCU

238
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCCACAAUGCAAAUCUUCUAUAG

GAUUAG-GCCACA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAAGCCACAAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCCACA

239
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACUCUCAUGCAAAUCUUCUAUAG

GAUUAG-AAUUGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAAAAUUGAAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-ACUCUC

240
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUGUACAUGCAAAUCUUCUAUAG

GAUUAG-GGACAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGGACAGAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUGUAC

241
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGCGCUAUGCAAAUCUUCUAUAG

GAUUAG-AAACAA
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUCUCUGAAAAACAAAUC

loop-symmetric_

CUUUUG-AGCGCU

242
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUGUUGAUGCAAAUCUUCUAUA

GAUUAG-GCCUAG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAAGCCUAGAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAUGUU

243
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAAUCCGAUGCAAAUCUUCUAUAG

GAUUAG-GGACGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAAGGACGAAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAAUCC

244
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUUAGUGAUGCAAAUCUUCUAUA

GAUUAG-AUCCAA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGAAAUCCAAAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUUAGU

245
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUAUCGAUGCAAAUCUUCUAUAG

GAUUAG-GCCCGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAAGCCCGAAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAUAUC

246
-12_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUGUACGAUGCAAAUCUUCUAUAG

GAUUAG-GAAGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUCUCUGAAGAAGAGAUC

loop-symmetric_

UUUUGU-CUGUAC

247
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-UAACCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUAACCGCAUC

A-C

248
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-CCAGGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACCAGGGCAUC

A-C

249
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-UUGUAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUGUAGCAUC

A-C

250
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-CAAUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACAAUACCAUC

A-C

251
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-UUCGUG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGAUUCGUGCAUC

252
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-UAAUCC
AGCGGUCAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUAAUCCCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-AGCGGU

253
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-UAAUUG
UCAGGUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUAAUUGCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UCAGGU

254
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-UCCUCG
ACGGGUCAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUCCUCGCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-ACGGGU

255
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-CGGGGA
ACAAAUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACGGGGACAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-ACAAAU

256
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AUUAGU-CAGCAA
ACGGGUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCUCUGACAGCAACAUC

loop-symmetric_

UGGAUC-ACGGGU

257
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

AUUAGU-CAGUUA
ACUAGACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGACAGUUACAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CACUAG

258
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

AUUAGU-CAGAAG
UUACAACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACAGAAGCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-AUUACA

259
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

AUUAGU-CGGUUC
CUUAGACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGACGGUUCCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CCUUAG

260
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

AUUAGU-CCCCAC
AUGAGACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACCCCACCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UAUGAG

261
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

AUUAGU-UCCUUG
CCAAGACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUCUCUGAUCCUUGCAUC

loop-symmetric_

GGAUCC-ACCAAG

262
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

AUUAGU-UGACAA
UCGGCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUGACAACAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUUCGG

263
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

AUUAGU-CAUUUG
AGAACACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACAUUUGCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUAGAA

264
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCA

AUUAGU-CAGGUG
CCGGCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCUGACAGGUGCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CACCGG

265
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

AUUAGU-CAUCUG
ACAGCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACAUCUGCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUACAG

266
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

AUUAGU-UCCUUC
AUGACACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCUCUGAUCCUUCCAUC

loop-symmetric_

GAUCCU-UUAUGA

267
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUC

AUUAGU-UUCUCA
GCACCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUGAUUCUCACAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CUCGCA

268
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACGA

AUUAGU-CGGUGC
AACCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCUGACGGUGCCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CGAAAC

269
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACGC

AUUAGU-UGGUGC
ACGCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCUGAUGGUGCCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CGCACG

270
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGUC

AUUAGU-UACCAC
ACCCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCUGAUACCACCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GUCACC

271
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUG

AUUAGU-CAACGG
UCGCCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUAUCUCUGACAACGGCAUC

loop-symmetric_

AUCCUA-AUGUCG

272
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCAAU

AUUAGU-UGAAGG
GCUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUGAUGAAGGCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CAAUGC

273
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCAUC

AUUAGU-CAGUAC
AUUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACAGUACCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CAUCAU

274
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCGAA

AUUAGU-UGUUCG
GUUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUGUUCGCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CGAAGU

275
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCGCC

AUUAGU-UAGCCA
AUUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUAGCCACAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CGCCAU

276
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGAA

AUUAGU-CGACCG
UUUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAUCUCUGACGACCGCAUC

loop-symmetric_

UCCUAU-UGAAUU

277
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGCCGA

AUUAGU-UAAAAA
AAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUAAAAACAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GCCGAA

278
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUGUC

AUUAGU-CCAUGC
CAUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCUGACCAUGCCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GUGUCC

279
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCCCGC

AUUAGU-UCAACC
CAUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCUGAUCAACCCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CCCGCC

280
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUUCC

AUUAGU-UAGUCC
CAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUCUCUGAUAGUCCCAUC

loop-symmetric_

CCUAUA-GUUCCC

281
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGAACA

AUUAGU-UCCCGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUCCCGACAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AGAACA

282
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGCGUC

AUUAGU-UGUCCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUGUCCCCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AGCGUC

283
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCAACA

AUUAGU-UUUCAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUUCAACAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCAACA

284
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGACAC

AUUAGU-UGGCCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUGGCCGCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGACAC

285
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAUCAUA

AUUAGU-CCAGCG
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCUCUGACCAGCGCAUC

loop-symmetric_

CUAUAG-AUCAUA

286
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGGAAU

AUUAGU-UACCGC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAUACCGCCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGGAAU

287
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAUGGAU

AUUAGU-UAGUUG
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGAUAGUUGCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AUGGAU

288
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCACGAUG

AUUAGU-CAUCGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGACAUCGGCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CACGAU

289
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGGUUU

AUUAGU-UUCCCG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAUUCCCGCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGGUUU

290
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAAUCCG

AUUAGU-CGAUUA
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCUCUGACGAUUACAUC

loop-symmetric_

UAUAGA-CAAUCC

291
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCUCCAAG

AUUAGU-UGAGCA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUGAGCACAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CCUCCA

292
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCUGGUGAG

AUUAGU-UUCGAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUUCGAGCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CUGGUG

293
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCAACGCAG

AUUAGU-CCAAGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGACCAAGACAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CAACGC

294
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAAAAAAA

AUUAGU-UUACCC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAUUACCCCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AAAAAA

295
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAGUAGCAG

AUUAGU-UCCUCA
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUCUCUGAUCCUCACAUC

loop-symmetric_

AUAGAA-AGUAGC

296
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAGUACUA

AUUAGU-UGGAGG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAUGGAGGCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAGUAC

297
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCGAAUUA

AUUAGU-CAGCAC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGACAGCACCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCGAAU

298
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGAACAUUA

AUUAGU-UUGUCG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGAUUGUCGCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GAACAU

299
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUCAAUUA

AUUAGU-UGUCCA
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUAUCUCUGAUGUCCACAUC

loop-symmetric_

UAGAAG-AUCAAU

300
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUAUAGAUA

AUUAGU-UAGGCC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGAUAGGCCCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AUAUAG

301
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGUACCAAUAG

AUUAGU-UGUUCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUGUUCGCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GUACCA

302
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACGUAAAAUA

AUUAGU-CAUUCC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGACAUUCCCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CGUAAA

303
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAAGAAAUA

AUUAGU-UGUCAC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAUGUCACCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAAGAA

304
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGGGGGAUA

AUUAGU-UCCAGG
GGAUCCACAGGGAGGGGGCAUUUUAA

30_6-6_internal_
UAUAUCUCUGAUCCAGGCAUC

loop-symmetric_

AGAAGA-AGGGGG

305
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAGCGAUAUAG

AUUAGU-UCCCGG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUCCCGGCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAGCGA

306
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACUACAGUAUAG

AUUAGU-CAGCAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACAGCAGCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CUACAG

307
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGAGAGUAUA

AUUAGU-CGAAAA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGACGAAAACAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UGAGAG

308
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCGCAGUAUAG

AUUAGU-CAGUUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACAGUUCCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCGCAG

309
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGUGAGUAUA

AUUAGU-CAGUCC
GGAUCCACAGGGAGGGGGCAUUUUAA

31_6-6_internal_
UAUAUCUCUGACAGUCCCAUC

loop-symmetric_

GAAGAU-UGUGAG

310
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACGCAAGCUAUAG

AUUAGU-UGACAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUGACAGCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CGCAAG

311
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCAGUGCUAUAG

AUUAGU-UUCGGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUUCGGACAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCAGUG

312
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCUAUGCUAUAG

AUUAGU-UUAAAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUAAAGCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCUAUG

313
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCAGGCCUAUAG

AUUAGU-UAGCGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUAGCGCCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCAGGC

314
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUAUACCUAUAG

AUUAGU-UAGUCC
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAUCUCUGAUAGUCCCAUC

loop-symmetric_

AAGAUU-CUAUAC

315
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUAGACUCUAUAG

AUUAGU-CGGUAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGACGGUACCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUAGAC

316
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUGCGACUCUAUAG

AUUAGU-UACACG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUACACGCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UGCGAC

317
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUUGACUCUAUAG

AUUAGU-UUAUGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUAUGCCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUUGAC

318
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCCAAGUCUAUAG

AUUAGU-CGAGGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACGAGGACAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCCAAG

319
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCGUAUAUCUAUAG

AUUAGU-UGCAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCUCUGAUGCAUCCAUC

loop-symmetric_

AGAUUU-CGUAUA

320
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUCGAAUUCUAUA

AUUAGU-CAGCGA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGACAGCGACAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUCGAA

321
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCCCCGUUCUAUAG

AUUAGU-UUAUUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUAUUACAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCCCCG

322
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGUGAGUUCUAUA

AUUAGU-UGCCUC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGAUGCCUCCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AGUGAG

323
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCCCGGUUCUAUAG

AUUAGU-CGGCGA
GAUCCACAGGGAGGGGGCAUUUUAAU

34_6-6_internal_
AUAUCUCUGACGGCGACAUC

loop-symmetric_

GAUUUG-GCCCGG

324
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUCUGACUUCUAUAG

AUUAGU-CGGUUA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGACGGUUACAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUCUGA

325
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAUUCCACUUCUAUAG

AUUAGU-UUGCGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUUGCGCCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AUUCCA

326
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUGUUCCUUCUAUAG

AUUAGU-UUACAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUACACCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUGUUC

327
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAAUUGCCUUCUAUAG

AUUAGU-CAACGA
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUAUCUCUGACAACGACAUC

loop-symmetric_

AUUUGC-AAUUGC

328
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACUUUCUCUUCUAUAG

AUUAGU-UGUUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUGUUCCCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-ACUUUC

329
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGUCCUCUCUUCUAUAG

AUUAGU-UAGCAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUAGCAACAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GUCCUC

330
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACAGUGUUCUUCUAUAG

AUUAGU-UAAUCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUAAUCCCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CAGUGU

331
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAGGUUUCUUCUAUA

AUUAGU-UAUCCA
GGAUCCACAGGGAGGGGGCAUUUUAA

36_6-6_internal_
UAUAUCUCUGAUAUCCACAUC

loop-symmetric_

UUUGCA-GAGGUU

332
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCUAACAUCUUCUAUAG

AUUAGU-UGCAUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUGCAUCCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCUAAC

333
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCCUUUUAUCUUCUAUAG

AUUAGU-CGGUUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACGGUUACAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CCUUUU

334
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCAAUCAUCUUCUAUAG

AUUAGU-UUCUUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUCUUCCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCAAUC

335
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUUAACUAUCUUCUAUAG

AUUAGU-CAUUCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACAUUCCCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UUAACU

336
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCACCCUAUCUUCUAUAG

AUUAGU-CAAGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUCUCUGACAAGGGCAUC

loop-symmetric_

UUGCAU-CACCCU

337
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCAAGUAAUCUUCUAUAG

AUUAGU-UCCAUA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUCCAUACAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CCAAGU

338
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUACUCAAUCUUCUAUAG

AUUAGU-CCCGCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACCCGCCCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUACUC

339
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUACCUAAUCUUCUAUAG

AUUAGU-UAAGUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUAAGUACAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUACCU

340
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUUAUCAAUCUUCUAUAG

AUUAGU-CAGGCA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACAGGCACAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UUUAUC

341
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUCUAUAAUCUUCUAUAG

AUUAGU-UUCUUG
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCUCUGAUUCUUGCAUC

loop-symmetric_

UGCAUC-AUCUAU

342
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUUAGAAAAUCUUCUAUAG

AUUAGU-UGGGCC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUGGGCCCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUUAGA

343
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCAAAAAAAUCUUCUAUAG

AUUAGU-UUCUUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUUCUUGCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UCAAAA

344
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCGCCAAAAUCUUCUAUAG

AUUAGU-UUACGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUACGACAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UCGCCA

345
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUAACGAAAUCUUCUAUAG

AUUAGU-UCAUGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUCAUGCCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUAACG

346
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCAGUAAAAUCUUCUAUAG

AUUAGU-CAACCC
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUCUCUGACAACCCCAUC

loop-symmetric_

GCAUCU-UCAGUA

347
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACAUUUUCAAAUCUUCUAUAG

AUUAGU-UACCUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUACCUGCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CAUUUU

348
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACACCUUCAAAUCUUCUAUAG

AUUAGU-CAGUCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACAGUCGCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CACCUU

349
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCAAAACAAAUCUUCUAUAG

AUUAGU-UUCUUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGAUUCUUCCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCAAAA

350
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUUCAACCAAAUCUUCUAUAG

AUUAGU-CGGACA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACGGACACAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UUCAAC

351
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUAAUCCCAAAUCUUCUAUAG

AUUAGU-UUCGGA
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAUCUCUGAUUCGGACAUC

loop-symmetric_

CAUCUU-UAAUCC

352
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUCCCCGCAAAUCUUCUAUAG

AUUAGU-UAAGUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUAAGUCCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUCCCC

353
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCGUGCGCAAAUCUUCUAUAG

AUUAGU-CAGAGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGACAGAGGCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCGUGC

354
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUAGUAAGCAAAUCUUCUAUAG

AUUAGU-UUCAAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUUCAAACAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UAGUAA

355
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUGUCGGCAAAUCUUCUAUAG

AUUAGU-UCACGG
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCUCUGAUCACGGCAUC

loop-symmetric_

AUCUUU-UUGUCG

356
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCCUUUUGCAAAUCUUCUAUAG

AUUAGU-CGACCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGACGACCGCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCCUUU

357
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCACUUUGCAAAUCUUCUAUAG

AUUAGU-UUCAUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUUCAUACAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCACUU

358
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCCCUCUGCAAAUCUUCUAUAG

AUUAGU-CCCUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGACCCUCGCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCCCUC

359
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUCACCUGCAAAUCUUCUAUAG

AUUAGU-UAGCAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUAGCACCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UUCACC

360
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUAUCAUUGCAAAUCUUCUAUAG

AUUAGU-UGCAUA
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCUCUGAUGCAUACAUC

loop-symmetric_

UCUUUU-UAUCAU

361
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCCAUAUGCAAAUCUUCUAUAG

AUUAGU-UGCAUA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGAUGCAUACAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCCAU

362
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAAUCCCAUGCAAAUCUUCUAUAG

AUUAGU-CCAUGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGACCAUGCCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AAUCCC

363
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGCAUUAUGCAAAUCUUCUAUAG

AUUAGU-UGCAGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGAUGCAGCCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AGCAUU

364
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACCCCAAUGCAAAUCUUCUAUAG

AUUAGU-CAUCGG
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUCUCUGACAUCGGCAUC

loop-symmetric_

CUUUUG-ACCCCA

365
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAACCUGAUGCAAAUCUUCUAUAG

AUUAGU-CCAAAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGACCAAAGCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAACCU

366
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUGGUCGAUGCAAAUCUUCUAUAG

AUUAGU-UAAGCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGAUAAGCCCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUGGUC

367
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUCUUUGAUGCAAAUCUUCUAUAG

AUUAGU-CCAACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGACCAACCCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUCUUU

368
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUCUACGAUGCAAAUCUUCUAUAG

AUUAGU-CGGCCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGACGGCCCCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUCUAC

369
-11_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUGUGUGAUGCAAAUCUUCUAUA

AUUAGU-CAUUCC
GGAUCCACAGGGAGGGGGCAUUUUAA

44_6-6_internal_
UAUAUCUCUGACAUUCCCAUC

loop-symmetric_

UUUUGU-UUGUGU

370
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CCCAGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCCCAGCUCAUC

A-C

371
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-UUUCUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUUCUCUCAUC

A-C

372
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CCCAUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCCCAUCUCAUC

A-C

373
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CCUCGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCCUCGCUCAUC

A-C

374
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CGUACC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUGCGUACCUCAUC

375
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-UUGAUU
UGCGGUCAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUUGAUUUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UGCGGU

376
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CUUUCC
UACAAUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCUUUCCUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UACAAU

377
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-UCGGGU
UCAUAUCAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUCGGGUUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UCAUAU

378
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CGUACC
ACUAAUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCGUACCUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-ACUAAU

379
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUAGUU-CAAGAU
AACAAUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCUCUGCAAGAUUCAUC

loop-symmetric_

UGGAUC-AACAAU

380
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UUAGUU-UGUUCC
AUGAAACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUGUUCCUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CAUGAA

381
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

UUAGUU-UUUGUU
CUGCAACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUUGUUUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UCUGCA

382
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UUAGUU-UUAACC
CCAAGACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUUAACCUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CCCAAG

383
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

UUAGUU-UCAGUC
UUGAGACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUCAGUCUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-AUUGAG

384
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCG

UUAGUU-UGAGUU
CUAGCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUGAGUUUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CGCUAG

385
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

UUAGUU-UUGGGC
CCAACACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCUGUUGGGCUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUCCAA

386
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

UUAGUU-UGAGAC
AAAGCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUGAGACUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UAAAAG

387
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

UUAGUU-CGUAUU
CGAACACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCGUAUUUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCCGAA

388
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCA

UUAGUU-CGGGAU
UGCGCACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCUCUGCGGGAUUCAUC

loop-symmetric_

GAUCCU-CAUGCG

389
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACCC

UUAGUU-CCCACC
UGGCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCCCACCUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CCCUGG

390
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAAA

UUAGUU-UCCCGC
UCCCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCUGUCCCGCUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AAAUCC

391
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUC

UUAGUU-UUAAGU
AUGCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUUAAGUUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CUCAUG

392
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUU

UUAGUU-UGUCUU
AUGCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUGUCUUUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AUUAUG

393
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGGC

UUAGUU-CCACCU
CUCCCACAGGGAGGGGGCAUUUUAAUA

23_6-6_internal_
UAUCUCUGCCACCUUCAUC

loop-symmetric_

AUCCUA-GGCCUC

394
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUCAU

UUAGUU-UUACAC
CCUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUGUUACACUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UCAUCC

395
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCGU

UUAGUU-UUGCCU
UUUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUGCCUUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCGUUU

396
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGCC

UUAGUU-CGGAAC
GUUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCGGAACUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGCCGU

397
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUCCA

UUAGUU-CGAUCC
AUUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCGAUCCUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UCCAAU

398
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCAUU

UUAGUU-UGUCGU
UUUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAUCUCUGUGUCGUUCAUC

loop-symmetric_

UCCUAU-CAUUUU

399
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGCCGC

UUAGUU-UCGGAC
AAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUCGGACUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GCCGCA

400
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAGCUA

UUAGUU-CCAAAU
UAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCCAAAUUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AGCUAU

401
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGAAAC

UUAGUU-CUGGUU
UAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCUGGUUUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GAAACU

402
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCGAUU

UUAGUU-UCAAUC
CAUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCUGUCAAUCUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CGAUUC

403
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCCUCA

UUAGUU-UUGGAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUUGGAUUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCCUCA

404
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAAAGCU

UUAGUU-UCGUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUCGUCCUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AAAGCU

405
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACCGAA

UUAGUU-CCGUCU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCCGUCUUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-ACCGAA

406
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAUCCUC

UUAGUU-UCAAGU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUCAAGUUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AUCCUC

407
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGUGCA

UUAGUU-CGGAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCUCUGCGGAUCUCAUC

loop-symmetric_

CUAUAG-AGUGCA

408
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAACCCCG

UUAGUU-CCUCGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCCUCGCUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AACCCC

409
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGGAGCG

UUAGUU-UUACAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUACAUUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGGAGC

410
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCACGAUG

UUAGUU-UGAGCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUGAGCCUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CACGAU

411
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAUCCUG

UUAGUU-CGUAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCUCUGCGUAUCUCAUC

loop-symmetric_

UAUAGA-CAUCCU

412
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAAUACAAG

UUAGUU-CGGAUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCGGAUCUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AAUACA

413
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGAGAGA

UUAGUU-CCAGGC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGCCAGGCUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GGAGAG

414
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCGGCGCAG

UUAGUU-CAGAUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCAGAUUUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CGGCGC

415
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCGCAAAG

UUAGUU-UAAAGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUAAAGCUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GCGCAA

416
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGUGGUGA

UUAGUU-CCGAGC
GGAUCCACAGGGAGGGGGCAUUUUAA

28_6-6_internal_
UAUAUCUCUGCCGAGCUCAUC

loop-symmetric_

AUAGAA-GUGGUG

417
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCAUUUUA

UUAGUU-UUAAAC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGUUAAACUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCAUUU

418
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGGAAUUA

UUAGUU-UGAACC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUGUGAACCUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GGGAAU

419
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCUAAUUA

UUAGUU-UCACCC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGUCACCCUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCUAAU

420
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUGGAUUA

UUAGUU-CCGGUU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGCCGGUUUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AUGGAU

421
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAUACCUAG

UUAGUU-UUUAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

29_6-6_internal_
AUAUCUCUGUUUAUCUCAUC

loop-symmetric_

UAGAAG-AAUACC

422
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAGCACAUAG

UUAGUU-CUGGAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCUGGAUUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAGCAC

423
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAACAAACAUAG

UUAGUU-CCCCCU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCCCCCUUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-ACAAAC

424
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGAGGCAUA

UUAGUU-CUUGCC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGCUUGCCUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGAGGC

425
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACACGGCAUAG

UUAGUU-UCGGUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUCGGUUUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CACGGC

426
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUUAGAAUA

UUAGUU-UUGCAU
GGAUCCACAGGGAGGGGGCAUUUUAA

30_6-6_internal_
UAUAUCUCUGUUGCAUUCAUC

loop-symmetric_

AGAAGA-AUUAGA

427
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUAAGCGUAUA

UUAGUU-CCCAUC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGCCCAUCUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UAAGCG

428
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAUACAUAUAG

UUAGUU-CGUGAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCGUGAUUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAUACA

429
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGUAAGUAUA

UUAGUU-UCAUCU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGUCAUCUUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UGUAAG

430
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACUAAAGUAUA

UUAGUU-UAAAGC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGUAAAGCUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CUAAAG

431
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUUGCUAUAUA

UUAGUU-UUUACC
GGAUCCACAGGGAGGGGGCAUUUUAA

31_6-6_internal_
UAUAUCUCUGUUUACCUCAUC

loop-symmetric_

GAAGAU-UUGCUA

432
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCAUAACUAUAG

UUAGUU-UCAAGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUCAAGUUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCAUAA

433
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCUAAGCUAUAG

UUAGUU-CCCCCU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCCCCCUUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCUAAG

434
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCGAACCUAUAG

UUAGUU-CCCCAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCCCCAUUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCGAAC

435
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACGAAACCUAUAG

UUAGUU-UUGGCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUUGGCCUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CGAAAC

436
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCAGGGCUAUAG

UUAGUU-CUGGAU
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAUCUCUGCUGGAUUCAUC

loop-symmetric_

AAGAUU-UCAGGG

437
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCAGAGGUCUAUAG

UUAGUU-UUGAGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUUGAGUUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CAGAGG

438
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUCGGCUCUAUAG

UUAGUU-CGGGUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCGGGUCUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUCGGC

439
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCACUGUCUAUAG

UUAGUU-CUGGUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCUGGUUUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCACUG

440
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUAACGUCUAUAG

UUAGUU-UCAGUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUCAGUCUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUAACG

441
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCACAGUCUAUAG

UUAGUU-CGAAUU
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCUCUGCGAAUUUCAUC

loop-symmetric_

AGAUUU-CCACAG

442
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUGUAUUCUAUA

UUAGUU-UUUCUC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGUUUCUCUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUUGUA

443
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACUGCGUUCUAUAG

UUAGUU-UUACAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUACACUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACUGCG

444
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCCAGGUUCUAUAG

UUAGUU-UGAUCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUGAUCCUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCCAGG

445
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGUCAAUUCUAUA

UUAGUU-CUUAUC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUGCUUAUCUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AGUCAA

446
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCGCAGUUCUAUAG

UUAGUU-UCCAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

34_6-6_internal_
AUAUCUCUGUCCAUCUCAUC

loop-symmetric_

GAUUUG-GCGCAG

447
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAGUCACUUCUAUAG

UUAGUU-UUGGUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUUGGUUUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UAGUCA

448
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAUGUUCCUUCUAUAG

UUAGUU-UCAAAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUCAAAUUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AUGUUC

449
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAACGGCUUCUAUAG

UUAGUU-CGGAUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCGGAUCUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UAACGG

450
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUUUCACCUUCUAUAG

UUAGUU-UAAGGU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUAAGGUUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UUUCAC

451
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAAAUAGCUUCUAUA

UUAGUU-UUUAUU
GGAUCCACAGGGAGGGGGCAUUUUAA

35_6-6_internal_
UAUAUCUCUGUUUAUUUCAUC

loop-symmetric_

AUUUGC-AAAUAG

452
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAUUUAUUCUUCUAUA

UUAGUU-CCCACC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGCCCACCUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AUUUAU

453
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGUCCGCUCUUCUAUAG

UUAGUU-UUGGUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUGGUCUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GUCCGC

454
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACAUGUUCUUCUAUAG

UUAGUU-UAUAUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUAUAUCUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-ACAUGU

455
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCCCUUUCUUCUAUAG

UUAGUU-CGAAGU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCGAAGUUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCCCUU

456
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAGUCUUCUUCUAUAG

UUAGUU-UAGGGC
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AUAUCUCUGUAGGGCUCAUC

loop-symmetric_

UUUGCA-AAGUCU

457
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUAUAGUAUCUUCUAUA

UUAGUU-UUGCCC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUGUUGCCCUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UAUAGU

458
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUACUACAUCUUCUAUAG

UUAGUU-UGUGUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUGUGUUUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UACUAC

459
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGAUUCAUCUUCUAUAG

UUAGUU-CCCCCU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCCCCCUUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CGAUUC

460
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAAAUCAUCUUCUAUAG

UUAGUU-CCAAAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCCAAACUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CAAAUC

461
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUAAAAUAUCUUCUAUA

UUAGUU-UUAUCC
GGAUCCACAGGGAGGGGGCAUUUUAA

37_6-6_internal_
UAUAUCUCUGUUAUCCUCAUC

loop-symmetric_

UUGCAU-UAAAAU

462
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUCCACAAUCUUCUAUAG

UUAGUU-UAUCUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUAUCUCUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUCCAC

463
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUAACUAAUCUUCUAUAG

UUAGUU-UUGCAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUGCAUUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUAACU

464
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCACUUAAUCUUCUAUAG

UUAGUU-CCAGUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCCAGUUUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CCACUU

465
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUACUAUAAUCUUCUAUAG

UUAGUU-UUGUCU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUUGUCUUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UACUAU

466
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUCAACAAUCUUCUAUAG

UUAGUU-UCUUCC
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCUCUGUCUUCCUCAUC

loop-symmetric_

UGCAUC-AUCAAC

467
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUAGUAAAAUCUUCUAUAG

UUAGUU-CCGUCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCCGUCUUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUAGUA

468
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUUCAGAAAUCUUCUAUAG

UUAGUU-UUUCUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUUUCUCUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUUCAG

469
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUUGGAAAAUCUUCUAUA

UUAGUU-CUUAGU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUGCUUAGUUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUUGGA

470
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACACCAAAAAUCUUCUAUAG

UUAGUU-UUUGUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUUUGUCUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CACCAA

471
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUCUUAAAAUCUUCUAUAG

UUAGUU-CCAGUC
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUCUCUGCCAGUCUCAUC

loop-symmetric_

GCAUCU-UUCUUA

472
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUACACAAAUCUUCUAUAG

UUAGUU-UUGCAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUUGCACUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCUACA

473
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGAAAUCAAAUCUUCUAUAG

UUAGUU-CCACCU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCCACCUUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CGAAAU

474
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUACACUCAAAUCUUCUAUAG

UUAGUU-CCAAUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCCAAUCUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UACACU

475
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUUUAGCCAAAUCUUCUAUAG

UUAGUU-CAGGAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCAGGACUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UUUAGC

476
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGAAACCAAAUCUUCUAUAG

UUAGUU-UUUACC
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAUCUCUGUUUACCUCAUC

loop-symmetric_

CAUCUU-CGAAAC

477
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUUCCAGCAAAUCUUCUAUAG

UUAGUU-CUUAUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCUUAUUUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUUCCA

478
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACACGUGGCAAAUCUUCUAUAG

UUAGUU-CGGGGU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCGGGGUUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CACGUG

479
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCACACGCAAAUCUUCUAUAG

UUAGUU-UUUUCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUUUUCCUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCACAC

480
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCUUUCGCAAAUCUUCUAUAG

UUAGUU-UCAUCU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUCAUCUUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCUUUC

481
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCGCCGGCAAAUCUUCUAUAG

UUAGUU-CCCCCC
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCUCUGCCCCCCUCAUC

loop-symmetric_

AUCUUU-UCGCCG

482
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUACGCCUGCAAAUCUUCUAUAG

UUAGUU-UUACAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGUUACAUUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UACGCC

483
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCUGUCUGCAAAUCUUCUAUAG

UUAGUU-UCCACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGUCCACUUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCUGUC

484
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCCAUUUGCAAAUCUUCUAUAG

UUAGUU-UCUCGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUCUCGCUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCCAUU

485
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCCAUCUGCAAAUCUUCUAUAG

UUAGUU-UGUAUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUGUAUUUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCCAUC

486
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGUCCCUGCAAAUCUUCUAUAG

UUAGUU-CCAGUC
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCUCUGCCAGUCUCAUC

loop-symmetric_

UCUUUU-UGUCCC

487
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUCGCUAUGCAAAUCUUCUAUAG

UUAGUU-CCUCAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCCUCACUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUCGCU

488
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGCCAAAUGCAAAUCUUCUAUAG

UUAGUU-CCGUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCCGUCCUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AGCCAA

489
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUUCUCAUGCAAAUCUUCUAUAG

UUAGUU-UUUCUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGUUUCUUUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUUCUC

490
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCUCAUAUGCAAAUCUUCUAUAG

UUAGUU-CUUCUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGCUUCUCUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCUCAU

491
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAAGUUUAUGCAAAUCUUCUAUA

UUAGUU-UCGAGU
GGAUCCACAGGGAGGGGGCAUUUUAA

43_6-6_internal_
UAUAUCUCUGUCGAGUUCAUC

loop-symmetric_

CUUUUG-AAGUUU

492
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGGCAUGAUGCAAAUCUUCUAUAG

UUAGUU-CGAGGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUGCGAGGUUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGGCAU

493
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGUCUUGAUGCAAAUCUUCUAUAG

UUAGUU-CCUCUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUGCCUCUUUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGUCUU

494
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCCCUCCGAUGCAAAUCUUCUAUAG

UUAGUU-CGUACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUGCGUACCUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CCCUCC

495
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGCCUCGAUGCAAAUCUUCUAUAG

UUAGUU-UUGGUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUGUUGGUUUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGCCUC

496
-10_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUGCCGAUGCAAAUCUUCUAUAG

UUAGUU-CGGAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUCUCUGCGGAUCUCAUC

loop-symmetric_

UUUUGU-CUUGCC

497
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-AUUUAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUAUUUAUAUCAUC

A-C

498
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-UUGUAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUUGUACAUCAUC

A-C

499
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-CAUUUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUCAUUUUAUCAUC

A-C

500
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-CUCCAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCUCCACAUCAUC

A-C

501
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-UCAAAU
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCUUCAAAUAUCAUC

502
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-UUUUGC
ACUAUUCAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUUUUUGCAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-ACUAUU

503
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-UCCGAU
CGCUUUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUCCGAUAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CGCUUU

504
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-AUGUAU
AAGGAUCAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUAUGUAUAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-AAGGAU

505
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-ACGUCC
UCGGGUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUACGUCCAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UCGGGU

506
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UAGUUC-UUCACC
UACUUUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCUCUUUCACCAUCAUC

loop-symmetric_

UGGAUC-UACUUU

507
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

UAGUUC-UAUGGU
AGAAAACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUUAUGGUAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UAGAAA

508
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

UAGUUC-UUUUCC
CUACAACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUUUUCCAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UCUACA

509
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

UAGUUC-UUCCGC
CCUAAACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUUUCCGCAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-ACCUAA

510
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

UAGUUC-UCCCGC
CGCAGACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUUCCCGCAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-ACGCAG

511
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UAGUUC-AGUGAU
UUAGAACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUCUCUAGUGAUAUCAUC

loop-symmetric_

GGAUCC-CUUAGA

512
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUC

UAGUUC-AUCAUU
UCCGCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUAUCAUUAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UCUCCG

513
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCU

UAGUUC-UAUGAU
ACCACACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCUUAUGAUAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CUACCA

514
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

UAGUUC-UCCUCC
AUUACACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUUCCUCCAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UAAUUA

515
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

UAGUUC-AUGGGU
UGUACACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAUGGGUAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UAUGUA

516
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

UAGUUC-CAGUCC
CGCGCACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCUCUCAGUCCAUCAUC

loop-symmetric_

GAUCCU-UUCGCG

517
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUU

UAGUUC-CUCCAU
GCACCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUCUCCAUAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AUUGCA

518
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGAU

UAGUUC-CAUGCC
UAACCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUCAUGCCAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GAUUAA

519
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGUC

UAGUUC-UCCUCC
CUACCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCUUCCUCCAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GUCCUA

520
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGAC

UAGUUC-ACAGGU
AAACCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUACAGGUAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GACAAA

521
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGGC

UAGUUC-ACCGUU
UGGCCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUAUCUCUACCGUUAUCAUC

loop-symmetric_

AUCCUA-GGCUGG

522
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGAU

UAGUUC-CACCGC
UCUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUCACCGCAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGAUUC

523
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUUAC

UAGUUC-UAGUAU
AUUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUAGUAUAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UUACAU

524
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUUCA

UAGUUC-CCUCAU
UCUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCUCCUCAUAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UUCAUC

525
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCAA

UAGUUC-CCCGAU
UUUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCCCGAUAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCAAUU

526
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUUAA

UAGUUC-UUCCGC
UCUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAUCUCUUUCCGCAUCAUC

loop-symmetric_

UCCUAU-UUAAUC

527
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACUUU

UAGUUC-CUCGUU
CAUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUCUCUCGUUAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACUUUC

528
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUAUC

UAGUUC-UUCCGC
CAUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCUUUCCGCAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GUAUCC

529
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAUUCA

UAGUUC-UGUUCC
UAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUUGUUCCAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AUUCAU

530
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACUUC

UAGUUC-UUAAAU
CAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUCUCUUUAAAUAUCAUC

loop-symmetric_

CCUAUA-ACUUCC

531
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGACACC

UAGUUC-ACCAAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUACCAAUAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GACACC

532
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGAGGUC

UAGUUC-AGUUAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUAGUUACAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GAGGUC

533
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACUCUC

UAGUUC-CGUUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCGUUACAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-ACUCUC

534
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCAAAU

UAGUUC-CUUGGU
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCUCUCUUGGUAUCAUC

loop-symmetric_

CUAUAG-GCAAAU

535
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCACUUCG

UAGUUC-UUAGAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUUUAGAUAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CACUUC

536
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGCCUUG

UAGUUC-UUUGCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUUUGCCAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGCCUU

537
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCCCUCCG

UAGUUC-AUCGCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUAUCGCCAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CCCUCC

538
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGACACG

UAGUUC-AUUGUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAUUGUUAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AGACAC

539
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGUCCCUG

UAGUUC-UGUAGU
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCUCUUGUAGUAUCAUC

loop-symmetric_

UAUAGA-GUCCCU

540
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCGUUGAG

UAGUUC-AUCCCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUAUCCCUAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GCGUUG

541
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCGCACAG

UAGUUC-UCCGAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUCCGAUAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CCGCAC

542
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAGGAAGA

UAGUUC-UUCAGU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUUUCAGUAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AGGAAG

543
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAAGCCCAG

UAGUUC-AUCAAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAUCAAUAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AAGCCC

544
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCACAAGGAG

UAGUUC-AUUUAU
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUCUCUAUUUAUAUCAUC

loop-symmetric_

AUAGAA-ACAAGG

545
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGAGAGCUA

UAGUUC-UCAUAU
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUUCAUAUAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GAGAGC

546
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGCGGUUA

UAGUUC-UUUUCC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUUUUUCCAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GGCGGU

547
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGAGGUUA

UAGUUC-CUAAAU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUCUAAAUAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GGAGGU

548
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUACCACUUAG

UAGUUC-AUCCCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAUCCCCAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-ACCACU

549
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGCAGGCAUAG

UAGUUC-CCAGUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUCCAGUUAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GCAGGC

550
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGAGAGCAUA

UAGUUC-CCUGGU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUCCUGGUAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GAGAGC

551
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACGAGGAAUA

UAGUUC-CACCCC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUCACCCCAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CGAGGA

552
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGCCGAAUAG

UAGUUC-CAGUAU
GAUCCACAGGGAGGGGGCAUUUUAAU

30_6-6_internal_
AUAUCUCUCAGUAUAUCAUC

loop-symmetric_

AGAAGA-AGCCGA

553
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAACGAUAUAG

UAGUUC-AUGUUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUAUGUUCAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAACGA

554
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCAACGUAUAG

UAGUUC-CCCUUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUCCCUUCAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCAACG

555
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGACAAUAUA

UAGUUC-CCAAAU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUCCAAAUAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UGACAA

556
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACUGGUAUAUA

UAGUUC-CGCCGC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUCGCCGCAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CUGGUA

557
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGACGAUAUA

UAGUUC-UAUAAU
GGAUCCACAGGGAGGGGGCAUUUUAA

31_6-6_internal_
UAUAUCUCUUAUAAUAUCAUC

loop-symmetric_

GAAGAU-UGACGA

558
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUAAGGGCUAUA

UAGUUC-UUUAAU
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUUUUAAUAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UAAGGG

559
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUCAUCCUAUAG

UAGUUC-CCAAGU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUCCAAGUAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUCAUC

560
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCGAAACUAUAG

UAGUUC-AGUGAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAGUGAUAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCGAAA

561
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUGGAGACUAUA

UAGUUC-UAUUUU
GGAUCCACAGGGAGGGGGCAUUUUAA

32_6-6_internal_
UAUAUCUCUUAUUUUAUCAUC

loop-symmetric_

AAGAUU-UGGAGA

562
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCCAUGUCUAUAG

UAGUUC-UUCCCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUUUCCCUAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCCAUG

563
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCAUAACUCUAUAG

UAGUUC-ACCUUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUACCUUUAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CAUAAC

564
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUACAGUCUAUAG

UAGUUC-AUUUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAUUUACAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUACAG

565
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUGCCGUCUAUAG

UAGUUC-AUUAAU
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCUCUAUUAAUAUCAUC

loop-symmetric_

AGAUUU-UUGCCG

566
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAUUGGGUUCUAUA

UAGUUC-UCCACC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCUUCCACCAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AUUGGG

567
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUAUGGUUCUAUA

UAGUUC-UCUUAC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCUUCUUACAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUAUGG

568
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACCAGGUUCUAUAG

UAGUUC-UUUGGU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUUUUGGUAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACCAGG

569
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGCGAAUUCUAUA

UAGUUC-UUUUAC
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUAUCUCUUUUUACAUCAUC

loop-symmetric_

GAUUUG-AGCGAA

570
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAAUGGACUUCUAUA

UAGUUC-UAUAAU
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUUAUAAUAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AAUGGA

571
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAUCGUGCUUCUAUAG

UAGUUC-AUUCAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUAUUCAUAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AUCGUG

572
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUUCGUGCUUCUAUAG

UAGUUC-ACCCGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUACCCGCAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UUCGUG

573
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAUCCGACUUCUAUAG

UAGUUC-CACCAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCACCACAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AUCCGA

574
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUCCUACCUUCUAUAG

UAGUUC-CUCGGU
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUAUCUCUCUCGGUAUCAUC

loop-symmetric_

AUUUGC-UCCUAC

575
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCAUUCUCUUCUAUAG

UAGUUC-UCCCCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUUCCCCUAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCAUUC

576
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAAACCUCUUCUAUAG

UAGUUC-UCAAAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUCAAAUAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAAACC

577
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCGUUUUCUUCUAUAG

UAGUUC-CCUUAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUCCUUAUAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCGUUU

578
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAGUCCUCUUCUAUAG

UAGUUC-AUCUCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUAUCUCCAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GAGUCC

579
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUUGAUAUCUUCUAUAG

UAGUUC-CCUUGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUCCUUGCAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUUGAU

580
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGAACUAUCUUCUAUAG

UAGUUC-CCCUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUCCCUCCAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CGAACU

581
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUAUCCAUCUUCUAUAG

UAGUUC-UCUUGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUUCUUGCAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUAUCC

582
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCAGUUAUCUUCUAUAG

UAGUUC-CGCAGU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCGCAGUAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCAGUU

583
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUUUGACAUCUUCUAUAG

UAGUUC-AUUAUU
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUCUCUAUUAUUAUCAUC

loop-symmetric_

UUGCAU-UUUGAC

584
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUAUCUAAUCUUCUAUAG

UAGUUC-CCUUCC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUCCUUCCAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUAUCU

585
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACAGAAUAAUCUUCUAUAG

UAGUUC-UUCGCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUUCGCCAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CAGAAU

586
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCCAAUAAUCUUCUAUAG

UAGUUC-UCCUCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUUCCUCCAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCCAAU

587
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCCAAUAAUCUUCUAUAG

UAGUUC-ACAGGU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUACAGGUAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CCCAAU

588
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUUAUCAAUCUUCUAUAG

UAGUUC-UUCGGU
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCUCUUUCGGUAUCAUC

loop-symmetric_

UGCAUC-CUUAUC

589
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUUAAAAAAUCUUCUAUA

UAGUUC-ACCCAC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCUACCCACAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUUAAA

590
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACACCGAAAAUCUUCUAUAG

UAGUUC-UAGUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUAGUCCAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CACCGA

591
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUAAAUAAAAUCUUCUAUA

UAGUUC-CAUGCC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUCAUGCCAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UAAAUA

592
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUUACGAAAUCUUCUAUAG

UAGUUC-CCGUUU
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUCUCUCCGUUUAUCAUC

loop-symmetric_

GCAUCU-CUUACG

593
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCCUCCCAAAUCUUCUAUAG

UAGUUC-CGUGAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUCGUGAUAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCCUCC

594
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUUCCCAAAUCUUCUAUAG

UAGUUC-UCUUGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUCUUGCAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCUUCC

595
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUUCCAACAAAUCUUCUAUAG

UAGUUC-AUCCAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUAUCCAUAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UUCCAA

596
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGCGACCAAAUCUUCUAUAG

UAGUUC-UAUGAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUUAUGAUAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CGCGAC

597
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCACAUCAAAUCUUCUAUAG

UAGUUC-CCUGUU
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAUCUCUCCUGUUAUCAUC

loop-symmetric_

CAUCUU-CCACAU

598
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACACAUGGCAAAUCUUCUAUAG

UAGUUC-CCGGGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUCCGGGUAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CACAUG

599
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUGUUAGCAAAUCUUCUAUAG

UAGUUC-AUCCGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUAUCCGCAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CUGUUA

600
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUAUCAGCAAAUCUUCUAUAG

UAGUUC-CACCGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUCACCGCAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CUAUCA

601
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUUCAAGCAAAUCUUCUAUAG

UAGUUC-CCCCGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCCCCGCAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CUUCAA

602
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACAUCGCGCAAAUCUUCUAUAG

UAGUUC-UUCGGU
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCUCUUUCGGUAUCAUC

loop-symmetric_

AUCUUU-CAUCGC

603
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGCGAUUGCAAAUCUUCUAUAG

UAGUUC-UUCCGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUUUCCGCAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UGCGAU

604
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGUCUCUGCAAAUCUUCUAUAG

UAGUUC-CCUUGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUCCUUGCAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UGUCUC

605
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCAGUUUGCAAAUCUUCUAUAG

UAGUUC-UCGGUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUUCGGUUAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCAGUU

606
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCUCACUGCAAAUCUUCUAUAG

UAGUUC-AUUUUU
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCUCUAUUUUUAUCAUC

loop-symmetric_

UCUUUU-CCUCAC

607
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCCAUCAUGCAAAUCUUCUAUAG

UAGUUC-CUGUCC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUCUGUCCAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCCAUC

608
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAAUACUAUGCAAAUCUUCUAUAG

UAGUUC-UUCAGU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUUUCAGUAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AAUACU

609
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACUCAUAUGCAAAUCUUCUAUAG

UAGUUC-AUUUUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUAUUUUUAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-ACUCAU

610
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUGGCAAUGCAAAUCUUCUAUAG

UAGUUC-CGCCCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCUCGCCCCAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUGGCA

611
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAAAUCAAUGCAAAUCUUCUAUAG

UAGUUC-CUUAGU
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUCUCUCUUAGUAUCAUC

loop-symmetric_

CUUUUG-AAAUCA

612
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUGUCCGAUGCAAAUCUUCUAUAG

UAGUUC-AGUAGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCUAGUAGUAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUGUCC

613
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUACCGAUGCAAAUCUUCUAUAG

UAGUUC-CUCCGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCUCUCCGCAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAUACC

614
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUUUCGAUGCAAAUCUUCUAUAG

UAGUUC-UCCCAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCUUCCCACAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAUUUC

615
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGAUAUGAUGCAAAUCUUCUAUA

UAGUUC-AUUGCC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCUAUUGCCAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGAUAU

616
-9_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUUACGAUGCAAAUCUUCUAUAG

UAGUUC-AUCACC
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUCUCUAUCACCAUCAUC

loop-symmetric_

UUUUGU-UAUUAC

617
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-CUUCGG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCUUCGGAAUCAUC

A-C

618
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-AUCUAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAUCUAAAAUCAUC

A-C

619
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-CCACAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCCACAAAAUCAUC

A-C

620
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-GGUGAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGGUGAGAAUCAUC

A-C

621
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-CCCUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUCCCCUGGAAUCAUC

622
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-AUUUCG
CAAAUUCAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCAUUUCGAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CAAAUU

623
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-AACAAG
UGCAGUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAACAAGAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UGCAGU

624
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-AUCGUA
ACUGAUCAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCAUCGUAAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-ACUGAU

625
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-CAGUUC
AAGUGUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCAGUUCAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-AAGUGU

626
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGUUCA-CUCUGG
CCGGAUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCUCCUCUGGAAUCAUC

loop-symmetric_

UGGAUC-CCGGAU

627
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

AGUUCA-CCUCAA
UCAAAACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCCUCAAAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-AUCAAA

628
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

AGUUCA-GCCUGG
CUGCAACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCGCCUGGAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-ACUGCA

629
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

AGUUCA-GUUUAA
AGUGGACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCGUUUAAAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-AAGUGG

630
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

AGUUCA-GCAGGA
UUAUAACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGCAGGAAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UUUAUA

631
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

AGUUCA-CCCCGG
UGCGAACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUCUCCCCCGGAAUCAUC

loop-symmetric_

GGAUCC-UUGCGA

632
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

AGUUCA-GGUCCG
AAAACACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCGGUCCGAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UAAAAA

633
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

AGUUCA-CCGCAG
CACGCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCCCGCAGAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UACACG

634
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCU

AGUUCA-GGUUUC
AUAGCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCGGUUUCAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CUAUAG

635
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

AGUUCA-GAUUGA
CUGGCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGAUUGAAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCCUGG

636
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUC

AGUUCA-AUUUAG
CUUACACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCUCAUUUAGAAUCAUC

loop-symmetric_

GAUCCU-UCCUUA

637
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAAC

AGUUCA-GCGUUA
GUACCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCGCGUUAAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AACGUA

638
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACAA

AGUUCA-CCGCCC
AAACCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCCGCCCAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CAAAAA

639
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUC

AGUUCA-GCCCGA
GCGCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCGCCCGAAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CUCGCG

640
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUG

AGUUCA-GUUUUA
CACCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCGUUUUAAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AUGCAC

641
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACAU

AGUUCA-AUACCG
UCCCCACAGGGAGGGGGCAUUUUAAUA

23_6-6_internal_
UAUCUCAUACCGAAUCAUC

loop-symmetric_

AUCCUA-CAUUCC

642
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCUU

AGUUCA-AUUGUA
UUUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCAUUGUAAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCUUUU

643
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGCA

AGUUCA-CUAUGG
UUUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCUAUGGAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGCAUU

644
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCUC

AGUUCA-GCGUUG
CUUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUCGCGUUGAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCUCCU

645
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCUCU

AGUUCA-GACGAA
ACUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUCGACGAAAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CUCUAC

646
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCCU

AGUUCA-CUAUGG
UUUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAUCUCCUAUGGAAUCAUC

loop-symmetric_

UCCUAU-CCCUUU

647
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAAUCU

AGUUCA-CCGUCG
UAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCCGUCGAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AAUCUU

648
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCUCCG

AGUUCA-GUAUGG
CAUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUCGUAUGGAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CUCCGC

649
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGAUUC

AGUUCA-CAUUUC
AAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCAUUUCAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GAUUCA

650
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUCGC

AGUUCA-CUUUCG
UAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCUUUCGAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GUCGCU

651
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCGCAU

AGUUCA-ACUGUA
CAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUCUCACUGUAAAUCAUC

loop-symmetric_

CCUAUA-CGCAUC

652
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACCUGC

AGUUCA-AUUUAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAUUUAAAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-ACCUGC

653
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACGGCC

AGUUCA-AUUCCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCAUUCCCAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-ACGGCC

654
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGUAUC

AGUUCA-GUCGGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGUCGGGAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGUAUC

655
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAACGCU

AGUUCA-AACCGG
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCUCAACCGGAAUCAUC

loop-symmetric_

CUAUAG-AACGCU

656
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAGGACG

AGUUCA-ACGUUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCACGUUGAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CAGGAC

657
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAUAAGCG

AGUUCA-AUUUUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAUUUUCAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AUAAGC

658
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAUCGUG

AGUUCA-CCGUAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCCGUAGAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CAUCGU

659
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAAUUACG

AGUUCA-CAUCGA
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCUCCAUCGAAAUCAUC

loop-symmetric_

UAUAGA-AAUUAC

660
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGAUUAA

AGUUCA-AUCCCA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCAUCCCAAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GGAUUA

661
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCGCGCAG

AGUUCA-GCUCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCGCUCGAAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CCGCGC

662
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCUGGAGAG

AGUUCA-CUUUUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCUUUUAAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CUGGAG

663
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCAGUCAG

AGUUCA-CUUGGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCUUGGGAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CCAGUC

664
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGGAACAG

AGUUCA-AACCCG
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUCUCAACCCGAAUCAUC

loop-symmetric_

AUAGAA-GGGAAC

665
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUACCUUUUAG

AGUUCA-ACUCAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCACUCAGAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-ACCUUU

666
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGUAUUUA

AGUUCA-AAGUAA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCAAGUAAAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AGUAUU

667
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGACACUAG

AGUUCA-AAUCGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCAAUCGAAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GGACAC

668
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAGAUUUA

AGUUCA-AAGUUC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCAAGUUCAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAGAUU

669
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUAGUUUA

AGUUCA-GAUGUC
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUAUCUCGAUGUCAAUCAUC

loop-symmetric_

UAGAAG-AUAGUU

670
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAGGACAUAG

AGUUCA-CCCUCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCCCUCGAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAGGAC

671
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAGGUGAUA

AGUUCA-GGUUUC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCGGUUUCAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAGGUG

672
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAACCCAUAG

AGUUCA-CACCAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCACCAAAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAACCC

673
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGGGUAAAUA

AGUUCA-ACCAUG
GGAUCCACAGGGAGGGGGCAUUUUAA

30_6-6_internal_
UAUAUCUCACCAUGAAUCAUC

loop-symmetric_

AGAAGA-GGGUAA

674
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGUGAGUAUA

AGUUCA-GCAUUC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCGCAUUCAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UGUGAG

675
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCUAGGUAUAG

AGUUCA-AAAUCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAAAUCGAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCUAGG

676
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUCACAGUAUAG

AGUUCA-AUAUUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCAUAUUAAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UCACAG

677
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCUAAGUAUAG

AGUUCA-GGUGUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGGUGUAAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCUAAG

678
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGAAGGUAUA

AGUUCA-CCCUAG
GGAUCCACAGGGAGGGGGCAUUUUAA

31_6-6_internal_
UAUAUCUCCCCUAGAAUCAUC

loop-symmetric_

GAAGAU-CGAAGG

679
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUAACCCUAUAG

AGUUCA-ACCUAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCACCUAGAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUAACC

680
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUGGACCUAUAG

AGUUCA-ACCCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCACCCGAAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUGGAC

681
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUCAGGCUAUAG

AGUUCA-GCUCGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGCUCGAAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUCAGG

682
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUAAGACUAUAG

AGUUCA-ACCUUC
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAUCUCACCUUCAAUCAUC

loop-symmetric_

AAGAUU-CUAAGA

683
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCACGAUCUAUAG

AGUUCA-AAUGUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCAAUGUGAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCACGA

684
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCACUGUCUAUAG

AGUUCA-CACAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCACAGAAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCACUG

685
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUACCUGUCUAUAG

AGUUCA-CACGAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCACGAGAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UACCUG

686
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUACUAAUCUAUAG

AGUUCA-GCAUGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGCAUGAAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UACUAA

687
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUCGGGUCUAUAG

AGUUCA-ACAUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCUCACAUGGAAUCAUC

loop-symmetric_

AGAUUU-UUCGGG

688
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCUUGAUUCUAUA

AGUUCA-CUUCAG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUCCUUCAGAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCUUGA

689
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUAAAUUCUAUA

AGUUCA-ACUCGA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCACUCGAAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AAUAAA

690
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACCCAAUUCUAUAG

AGUUCA-GAUUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCGAUUCGAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACCCAA

691
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCGUUAUUCUAUA

AGUUCA-AUUUAA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCAUUUAAAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCGUUA

692
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUGAAUUCUAUA

AGUUCA-GCAUGG
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUAUCUCGCAUGGAAUCAUC

loop-symmetric_

GAUUUG-AAUGAA

693
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUUUCCACUUCUAUAG

AGUUCA-CACCAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCACCAAAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UUUCCA

694
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUCCCCUUCUAUAG

AGUUCA-ACUCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCACUCGAAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUUCCC

695
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCCCUAGCUUCUAUAG

AGUUCA-AUCGGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCAUCGGGAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CCCUAG

696
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUUCGUGCUUCUAUAG

AGUUCA-ACUUUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCACUUUCAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UUCGUG

697
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAGGUCGCUUCUAUAG

AGUUCA-CCUCCG
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUAUCUCCCUCCGAAUCAUC

loop-symmetric_

AUUUGC-AGGUCG

698
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACAGGUUUCUUCUAUAG

AGUUCA-GCUUAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCGCUUAAAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CAGGUU

699
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAAACUUCUUCUAUAG

AGUUCA-CUUCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCUUCGAAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GAAACU

700
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAAUUUUCUUCUAUA

AGUUCA-CCCUGG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUCCCCUGGAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAAUUU

701
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGUCUUCUCUUCUAUAG

AGUUCA-CUUUUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCUUUUGAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GUCUUC

702
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACUCUUUCUUCUAUAG

AGUUCA-AUUCCG
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AUAUCUCAUUCCGAAUCAUC

loop-symmetric_

UUUGCA-ACUCUU

703
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUAAGACAUCUUCUAUAG

AGUUCA-CCAUAG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCCAUAGAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UAAGAC

704
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGAUUCAUCUUCUAUAG

AGUUCA-GACCCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCGACCCCAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CGAUUC

705
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGAGUCAUCUUCUAUAG

AGUUCA-GGUCGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCGGUCGAAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CGAGUC

706
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAUAUCAUCUUCUAUAG

AGUUCA-GCCCCA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGCCCCAAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CAUAUC

707
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGUUUCAUCUUCUAUAG

AGUUCA-ACUGUG
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUCUCACUGUGAAUCAUC

loop-symmetric_

UUGCAU-CGUUUC

708
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUCACUAAUCUUCUAUAG

AGUUCA-AUUGGG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCAUUGGGAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AUCACU

709
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCACUUAAUCUUCUAUAG

AGUUCA-AAGUUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAAGUUAAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCACUU

710
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAAACUUAAUCUUCUAUAG

AGUUCA-CACCAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCACCAGAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AAACUU

711
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUUCUCAAUCUUCUAUAG

AGUUCA-ACAGGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCACAGGGAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AUUCUC

712
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUAAACAAUCUUCUAUAG

AGUUCA-CACGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCUCCACGAGAAUCAUC

loop-symmetric_

UGCAUC-AUAAAC

713
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUAUCAGAAAUCUUCUAUAG

AGUUCA-GUCUAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCGUCUAAAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UAUCAG

714
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCUGGAAAAUCUUCUAUAG

AGUUCA-AUACCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCAUACCCAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CCUGGA

715
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCUCGAAAAUCUUCUAUAG

AGUUCA-CCGUAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCCGUAAAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CCUCGA

716
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCUACAAAAUCUUCUAUAG

AGUUCA-ACACCC
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUCUCACACCCAAUCAUC

loop-symmetric_

GCAUCU-CCUACA

717
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCAGCCCAAAUCUUCUAUAG

AGUUCA-ACCAGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCACCAGAAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCAGCC

718
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGCAUUCAAAUCUUCUAUAG

AGUUCA-CCGUAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCCGUAAAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CGCAUU

719
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCCACACAAAUCUUCUAUAG

AGUUCA-CAUUUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCAUUUCAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCCACA

720
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACACACUCAAAUCUUCUAUAG

AGUUCA-ACACCA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCACACCAAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CACACU

721
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCCAUUCAAAUCUUCUAUAG

AGUUCA-GACAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAUCUCGACAAAAAUCAUC

loop-symmetric_

CAUCUU-CCCAUU

722
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCGCGCGCAAAUCUUCUAUAG

AGUUCA-CUCCGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCUCCGAAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCGCGC

723
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUGUCCAGCAAAUCUUCUAUAG

AGUUCA-GUUCAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCGUUCAAAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UGUCCA

724
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCUUGCGCAAAUCUUCUAUAG

AGUUCA-GUUUUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCGUUUUCAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCUUGC

725
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCGUCGGCAAAUCUUCUAUAG

AGUUCA-CUUCCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCUUCCGAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCGUCG

726
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUACCGGCAAAUCUUCUAUAG

AGUUCA-ACAGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCUCACAGAGAAUCAUC

loop-symmetric_

AUCUUU-UUACCG

727
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUCGAUUGCAAAUCUUCUAUAG

AGUUCA-ACUUCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCACUUCGAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUCGAU

728
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUCCAUUGCAAAUCUUCUAUAG

AGUUCA-CCACAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCCACAAAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUCCAU

729
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGCGCUUGCAAAUCUUCUAUAG

AGUUCA-ACACGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCACACGGAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UGCGCU

730
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUCGUUUGCAAAUCUUCUAUAG

AGUUCA-CAUUGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCCAUUGGAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UUCGUU

731
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUAUCCUGCAAAUCUUCUAUAG

AGUUCA-GGUGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCUCGGUGAGAAUCAUC

loop-symmetric_

UCUUUU-UUAUCC

732
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACGCUAAUGCAAAUCUUCUAUAG

AGUUCA-CACCAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCCACCAAAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-ACGCUA

733
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCUGCAUGCAAAUCUUCUAUAG

AGUUCA-CAUCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUCCAUCGAAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCUGC

734
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCCAAAUGCAAAUCUUCUAUAG

AGUUCA-CUCCCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCCUCCCCAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCCAA

735
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUUUGAAUGCAAAUCUUCUAUA

AGUUCA-GACAGG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUCGACAGGAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUUUGA

736
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUGUACAUGCAAAUCUUCUAUAG

AGUUCA-GCGGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUCUCGCGGGGAAUCAUC

loop-symmetric_

CUUUUG-AUGUAC

737
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGCCGUGAUGCAAAUCUUCUAUAG

AGUUCA-GGUUUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUCGGUUUCAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGCCGU

738
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUGGUUGAUGCAAAUCUUCUAUA

AGUUCA-GUUUAA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUCGUUUAAAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUGGUU

739
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCCCUUUGAUGCAAAUCUUCUAUAG

AGUUCA-AAGUAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUCAAGUAGAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CCCUUU

740
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUUUCGAUGCAAAUCUUCUAUAG

AGUUCA-GAUUCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUCGAUUCGAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUUUUC

741
-8_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGUGCUGAUGCAAAUCUUCUAUAG

AGUUCA-CCAUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUCUCCCAUGGAAUCAUC

loop-symmetric_

UUUUGU-UGUGCU

742
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-GGCUCA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGGCUCAUAAUCAUC

A-C

743
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-GCCGCA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGCCGCAUAAUCAUC

A-C

744
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-AACUAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAACUAAUAAUCAUC

A-C

745
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-AACACA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUAACACAUAAUCAUC

A-C

746
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-GGCCCG
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCUGGCCCGUAAUCAUC

747
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-AAAUUG
AAAAGUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAAAUUGUAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-AAAAGU

748
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-ACGUCG
CGCAAUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACGUCGUAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CGCAAU

749
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GUUCAG-GGUCAA
CUCAGUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCUGGUCAAUAAUCAUC

loop-symmetric_

UGGAUC-CUCAGU

750
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

GUUCAG-AAAUCG
CUGAGACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUAAAUCGUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-ACUGAG

751
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

GUUCAG-ACAAUA
CUCAAACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUACAAUAUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UCUCAA

752
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

GUUCAG-ACGCUA
UAAGAACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACGCUAUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UUAAGA

753
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

GUUCAG-AUUCCA
CCUAAACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUCUAUUCCAUAAUCAUC

loop-symmetric_

GGAUCC-ACCUAA

754
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

GUUCAG-AACCUG
UUGACACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUAACCUGUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UAUUGA

755
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

GUUCAG-GGUCGA
CUAGCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGGUCGAUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UACUAG

756
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCU

GUUCAG-GCUUGA
AGCACACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGCUUGAUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CUAGCA

757
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

GUUCAG-AAGCAA
CCCGCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUAAGCAAUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUCCCG

758
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCA

GUUCAG-AAUUCG
CCGGCACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCUAAUUCGUAAUCAUC

loop-symmetric_

GAUCCU-CACCGG

759
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGCC

GUUCAG-GGCUCA
UACCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUGGCUCAUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GCCUAC

760
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGCU

GUUCAG-GACCCA
CGCCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUGACCCAUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GCUCGC

761
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAACA

GUUCAG-GGCUUA
ACGCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUGGCUUAUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-ACAACG

762
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUC

GUUCAG-GAAGUG
AGCCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCUGAAGUGUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AUCAGC

763
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGCC

GUUCAG-AUCACG
ACCCCACAGGGAGGGGGCAUUUUAAUA

23_6-6_internal_
UAUCUAUCACGUAAUCAUC

loop-symmetric_

AUCCUA-GCCACC

764
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCUCG

GUUCAG-GCUCCG
UCUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUGCUCCGUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CUCGUC

765
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCAU

GUUCAG-GGUCCA
CUUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCUGGUCCAUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCAUCU

766
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCACA

GUUCAG-GGCGUG
AUUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGGCGUGUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CACAAU

767
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUAAC

GUUCAG-ACUUGA
GUUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACUUGAUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UAACGU

768
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGUA

GUUCAG-AAGCCA
UUUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAUCUAAGCCAUAAUCAUC

loop-symmetric_

UCCUAU-UGUAUU

769
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGACUC

GUUCAG-AAAAUA
CAUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCUAAAAUAUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GACUCC

770
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGAAGA

GUUCAG-GCCGCA
AAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGCCGCAUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GAAGAA

771
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAUCAC

GUUCAG-AAAUUA
CAUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCUAAAUUAUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AUCACC

772
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACGUU

GUUCAG-ACUAUG
UAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACUAUGUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACGUUU

773
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCCCUU

GUUCAG-AUUUUG
UAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUCUAUUUUGUAAUCAUC

loop-symmetric_

CCUAUA-CCCUUU

774
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGAAU

GUUCAG-ACUUGA
AGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUACUUGAUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGAAUA

775
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGAACGC

GUUCAG-GCACUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGCACUGUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GAACGC

776
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGAUAUC

GUUCAG-AGUUAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAGUUAAUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GAUAUC

777
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAUACCU

GUUCAG-AUAGUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUAUAGUGUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AUACCU

778
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGGCUC

GUUCAG-AACACA
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCUAACACAUAAUCAUC

loop-symmetric_

CUAUAG-AGGCUC

779
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGGCGUG

GUUCAG-AACUCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUAACUCGUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AGGCGU

780
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGUGUUU

GUUCAG-AGUUAA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUAGUUAAUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GUGUUU

781
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAUCAUG

GUUCAG-ACCUCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUACCUCAUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CAUCAU

782
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGCAGUG

GUUCAG-GGCCUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGGCCUAUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AGCAGU

783
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCCACUCG

GUUCAG-GACCUA
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCUGACCUAUAAUCAUC

loop-symmetric_

UAUAGA-CCACUC

784
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCAGUUCAG

GUUCAG-ACCUUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUACCUUGUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CAGUUC

785
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGAUCGAG

GUUCAG-AGUUUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAGUUUGUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GGAUCG

786
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGUGAUGA

GUUCAG-GGCGCG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUGGCGCGUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GUGAUG

787
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGACCUCAG

GUUCAG-GCGCGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGCGCGAUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GACCUC

788
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCGAGCAAG

GUUCAG-GCAGUG
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUCUGCAGUGUAAUCAUC

loop-symmetric_

AUAGAA-CGAGCA

789
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUGAUCUA

GUUCAG-AGUAUA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUAGUAUAUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AUGAUC

790
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGUGCCUAG

GUUCAG-GAUGUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGAUGUAUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GGUGCC

791
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUACAGGUUA

GUUCAG-AACGGA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUAACGGAUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-ACAGGU

792
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGACGUUUA

GUUCAG-ACGUUG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUACGUUGUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GACGUU

793
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUCAAUUA

GUUCAG-GACCUA
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUAUCUGACCUAUAAUCAUC

loop-symmetric_

UAGAAG-AUCAAU

794
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGAACGAUA

GUUCAG-ACCAUG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUACCAUGUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGAACG

795
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGGGUGGAUA

GUUCAG-AGCUCA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUAGCUCAUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GGGUGG

796
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGAGCCGAUAG

GUUCAG-GGCCUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGGCCUAUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GAGCCG

797
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUGGGGAUA

GUUCAG-GGCUUG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCUGGCUUGUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AUGGGG

798
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUACACAUAG

GUUCAG-GACUCA
GAUCCACAGGGAGGGGGCAUUUUAAU

30_6-6_internal_
AUAUCUGACUCAUAAUCAUC

loop-symmetric_

AGAAGA-AUACAC

799
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGGAAAUAUA

GUUCAG-AAUUUA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUAAUUUAUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGGAAA

800
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAGGUAUAUA

GUUCAG-GGCGGA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUGGCGGAUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAGGUA

801
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCGACGUAUAG

GUUCAG-AACUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAACUCGUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCGACG

802
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUUGCCAUAUAG

GUUCAG-AUUUUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUAUUUUGUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UUGCCA

803
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGUACAUAUAG

GUUCAG-GAUUGA
GAUCCACAGGGAGGGGGCAUUUUAAU

31_6-6_internal_
AUAUCUGAUUGAUAAUCAUC

loop-symmetric_

GAAGAU-CGUACA

804
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUAAGCACUAUAG

GUUCAG-GAAAUA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGAAAUAUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UAAGCA

805
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUAAGCCUAUAG

GUUCAG-GCAGUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGCAGUGUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUAAGC

806
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCUGCCCUAUAG

GUUCAG-GGCUAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGGCUAAUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCUGCC

807
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUACGCGCUAUAG

GUUCAG-ACCCCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACCCCGUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UACGCG

808
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCCACACUAUAG

GUUCAG-AACGCA
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAUCUAACGCAUAAUCAUC

loop-symmetric_

AAGAUU-UCCACA

809
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUAUAAAUCUAUA

GUUCAG-GCCCGA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUGCCCGAUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UAUAAA

810
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCUAUAUCUAUAG

GUUCAG-AGUUUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAGUUUAUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCUAUA

811
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCCGACUCUAUAG

GUUCAG-AGCCUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAGCCUAUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCCGAC

812
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCAUGACUCUAUAG

GUUCAG-AACCUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUAACCUGUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CAUGAC

813
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUUUAAUCUAUAG

GUUCAG-AACGCG
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCUAACGCGUAAUCAUC

loop-symmetric_

AGAUUU-CUUUAA

814
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGCGCAUUCUAUAG

GUUCAG-GCGCUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGCGCUGUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AGCGCA

815
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCCUGGUUCUAUAG

GUUCAG-GCCCCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGCCCCGUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCCUGG

816
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUAAGUUCUAUA

GUUCAG-AGAUUG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCUAGAUUGUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AAUAAG

817
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACUCGAUUCUAUAG

GUUCAG-GACUCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGACUCGUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACUCGA

818
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUCUGGUUCUAUA

GUUCAG-GGUCUG
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUAUCUGGUCUGUAAUCAUC

loop-symmetric_

GAUUUG-GUCUGG

819
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAGGUCGCUUCUAUAG

GUUCAG-GACAUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGACAUGUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AGGUCG

820
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAACUGCCUUCUAUAG

GUUCAG-AAUCCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAAUCCGUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AACUGC

821
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAUUCUACUUCUAUAG

GUUCAG-ACCUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUACCUCGUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AUUCUA

822
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAUGGGCUUCUAUA

GUUCAG-GCCCCG
GGAUCCACAGGGAGGGGGCAUUUUAA

35_6-6_internal_
UAUAUCUGCCCCGUAAUCAUC

loop-symmetric_

AUUUGC-UAUGGG

823
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAGUGUUCUUCUAUA

GUUCAG-AUUCCG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCUAUUCCGUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAGUGU

824
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAAUGUUCUUCUAUA

GUUCAG-GGUUGA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUGGUUGAUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAAUGU

825
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCUCUUUCUUCUAUAG

GUUCAG-AGUGUG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAGUGUGUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCUCUU

826
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAGGUCUCUUCUAUAG

GUUCAG-AGACGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUAGACGAUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAGGUC

827
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAAUGUUCUUCUAUA

GUUCAG-GGAUUG
GGAUCCACAGGGAGGGGGCAUUUUAA

36_6-6_internal_
UAUAUCUGGAUUGUAAUCAUC

loop-symmetric_

UUUGCA-GAAUGU

828
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUAUACAUCUUCUAUAG

GUUCAG-GAUUCA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGAUUCAUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUAUAC

829
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCCUUUUAUCUUCUAUAG

GUUCAG-AGCCUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAGCCUAUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CCUUUU

830
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUCAUUAUCUUCUAUAG

GUUCAG-AGUUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAGUUCGUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUCAUU

831
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUAAACCAUCUUCUAUAG

GUUCAG-ACUAUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACUAUGUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UAAACC

832
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGACCUAUCUUCUAUAG

GUUCAG-AGCCCG
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUCUAGCCCGUAAUCAUC

loop-symmetric_

UUGCAU-CGACCU

833
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUUCAUAAUCUUCUAUAG

GUUCAG-GCUCUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGCUCUGUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UUUCAU

834
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACAAUAUAAUCUUCUAUAG

GUUCAG-AGCAUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAGCAUAUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CAAUAU

835
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAACUUCUAAUCUUCUAUAG

GUUCAG-ACACCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUACACCAUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-ACUUCU

836
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAACUAACAAUCUUCUAUAG

GUUCAG-AUAAGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUAUAAGAUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-ACUAAC

837
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUCAACAAUCUUCUAUAG

GUUCAG-ACCUUG
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCUACCUUGUAAUCAUC

loop-symmetric_

UGCAUC-UUCAAC

838
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUCACAAAAUCUUCUAUAG

GUUCAG-GAUCCA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGAUCCAUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUCACA

839
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUAAGUAAAAUCUUCUAUA

GUUCAG-GACGCA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCUGACGCAUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UAAGUA

840
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUUCAGAAAUCUUCUAUAG

GUUCAG-GGAUUG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGGAUUGUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUUCAG

841
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCAAAGAAAUCUUCUAUAG

GUUCAG-ACGUGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUACGUGAUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UCAAAG

842
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCACUGAAAUCUUCUAUAG

GUUCAG-ACCGCA
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUCUACCGCAUAAUCAUC

loop-symmetric_

GCAUCU-UCACUG

843
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUCCACAAAUCUUCUAUAG

GUUCAG-GCCCAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGCCCAAUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCUCCA

844
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGUCAUCAAAUCUUCUAUAG

GUUCAG-AGAUUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAGAUUGUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CGUCAU

845
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCUAAACAAAUCUUCUAUAG

GUUCAG-AGUUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAGUUCGUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCUAAA

846
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCCUAGGCAAAUCUUCUAUAG

GUUCAG-GAAAGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGAAAGAUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCCUAG

847
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCAUGCGCAAAUCUUCUAUAG

GUUCAG-AGCGUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUAGCGUGUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCAUGC

848
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACGCCCAGCAAAUCUUCUAUAG

GUUCAG-AACUCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUAACUCGUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CGCCCA

849
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUAUCGGCAAAUCUUCUAUAG

GUUCAG-GCUCCA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGCUCCAUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CUAUCG

850
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCGUUCGCAAAUCUUCUAUAG

GUUCAG-GACUCG
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCUGACUCGUAAUCAUC

loop-symmetric_

AUCUUU-CCGUUC

851
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCGCUCUGCAAAUCUUCUAUAG

GUUCAG-ACGUCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUACGUCGUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCGCUC

852
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGCGUUUGCAAAUCUUCUAUAG

GUUCAG-GGUUUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGGUUUGUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UGCGUU

853
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUACCCUGCAAAUCUUCUAUAG

GUUCAG-GAAGUG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGAAGUGUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UUACCC

854
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUAUACUGCAAAUCUUCUAUAG

GUUCAG-GACUAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGACUAAUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUAUAC

855
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCAUCUCUGCAAAUCUUCUAUAG

GUUCAG-AGUCUG
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCUAGUCUGUAAUCAUC

loop-symmetric_

UCUUUU-CAUCUC

856
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGCUCAAUGCAAAUCUUCUAUAG

GUUCAG-GCAGUA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUGCAGUAUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AGCUCA

857
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCCCAAAUGCAAAUCUUCUAUAG

GUUCAG-GCAUCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGCAUCGUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCCCAA

858
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCAUAAUGCAAAUCUUCUAUAG

GUUCAG-GAUUUG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGAUUUGUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCAUA

859
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGUGCUAUGCAAAUCUUCUAUAG

GUUCAG-GAUCUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGAUCUAUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AGUGCU

860
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACGCUAAUGCAAAUCUUCUAUAG

GUUCAG-GGUUAA
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUCUGGUUAAUAAUCAUC

loop-symmetric_

CUUUUG-ACGCUA

861
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUGGCUGAUGCAAAUCUUCUAUAG

GUUCAG-AGCUUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCUAGCUUGUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUGGCU

862
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUUGCGAUGCAAAUCUUCUAUAG

GUUCAG-GGUAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCUGGUAGAUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUUUGC

863
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCCCGCCGAUGCAAAUCUUCUAUAG

GUUCAG-GACUAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCUGACUAAUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CCCGCC

864
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGGUGCGAUGCAAAUCUUCUAUAG

GUUCAG-GCGCUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCUGCGCUGUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGGUGC

865
-7_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAAUUCGAUGCAAAUCUUCUAUAG

GUUCAG-GACAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUCUGACAAAUAAUCAUC

loop-symmetric_

UUUUGU-UAAUUC

866
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-AUAAAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCAUAAAUCUAAUCAUC

A-C

867
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-AAGUGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAAGUGCCUAAUCAUC

A-C

868
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-AUACCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCAUACCCCUAAUCAUC

A-C

869
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-AAUCCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAAUCCCCUAAUCAUC

A-C

870
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-CAUACC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUCCAUACCCUAAUCAUC

871
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-GUUCAC
CUGUGUCAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGUUCACCUAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-CUGUGU

872
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-ACCUUC
ACAUAUCAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCACCUUCCUAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-ACAUAU

873
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-CAUUAU
AGCGUUCAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCCAUUAUCUAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-AGCGUU

874
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-AGGCUU
UUGUGUCAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAGGCUUCUAAUCAUC

A-C

20_6-6_internal_

loop-symmetric_

UGGAUC-UUGUGU

875
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UUCAGA-GGCGCU
AACGAUCAGGGAGGGGGCAUUUUAAU

20_6-6_internal_
AUAUCGGCGCUCUAAUCAUC

loop-symmetric_

UGGAUC-AACGAU

876
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

UUCAGA-GUUCAU
CACGGACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGUUCAUCUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UCACGG

877
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

UUCAGA-AAGUCC
GCAGGACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAAGUCCCUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-AGCAGG

878
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UUCAGA-CACUUU
AACAAACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCCACUUUCUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CAACAA

879
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UUCAGA-AUAUCC
UCAGAACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAUAUCCCUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-CUCAGA

880
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UUCAGA-ACCUUC
UCGAGACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUCACCUUCCUAAUCAUC

loop-symmetric_

GGAUCC-CUCGAG

881
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

UUCAGA-ACAAUC
CAAACACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCACAAUCCUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUCAAA

882
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCA

UUCAGA-GUAACU
CUAGCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGUAACUCUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CACUAG

883
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

UUCAGA-CACAUU
CUGACACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCCACAUUCUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUCUGA

884
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

UUCAGA-GGUUAU
UCCACACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCGGUUAUCUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCUCCA

885
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

UUCAGA-GGAACC
AACGCACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUCGGAACCCUAAUCAUC

loop-symmetric_

GAUCCU-CCAACG

886
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGUC

UUCAGA-AGGCUC
CAGCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCAGGCUCCUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GUCCAG

887
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAAU

UUCAGA-GGCCCU
UUCCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCGGCCCUCUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AAUUUC

888
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGUA

UUCAGA-AGGCCU
UCCCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCAGGCCUCUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GUAUCC

889
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAAA

UUCAGA-GGCCUC
AUACCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCGGCCUCCUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AAAAUA

890
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAGU

UUCAGA-AGACCC
AAACCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUAUCAGACCCCUAAUCAUC

loop-symmetric_

AUCCUA-AGUAAA

891
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCUUU

UUCAGA-AUACUC
UUUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCAUACUCCUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CUUUUU

892
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGAC

UUCAGA-AAUCGC
CUUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCAAUCGCCUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGACCU

893
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCGU

UUCAGA-AAUACU
ACUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUCAAUACUCUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCGUAC

894
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCUU

UUCAGA-AAGCUC
UCUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUCAAGCUCCUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCUUUC

895
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCGAC

UUCAGA-GACUUC
GCUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAUCGACUUCCUAAUCAUC

loop-symmetric_

UCCUAU-CGACGC

896
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAACGC

UUCAGA-CAAAGU
CAUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUCCAAAGUCUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AACGCC

897
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCAACG

UUCAGA-ACCUUU
CAUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUCACCUUUCUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CAACGC

898
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAGCGC

UUCAGA-AGCAUC
AAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCAGCAUCCUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AGCGCA

899
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUGUC

UUCAGA-CAAAUU
AAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCCAAAUUCUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GUGUCA

900
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGAAUA

UUCAGA-AGCUUU
AAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUCAGCUUUCUAAUCAUC

loop-symmetric_

CCUAUA-GAAUAA

901
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACGAAA

UUCAGA-GGAAUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGAAUCCUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-ACGAAA

902
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGUCCU

UUCAGA-GUAAUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGUAAUUCUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGUCCU

903
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCACCU

UUCAGA-GACACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGACACCCUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCACCU

904
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGGAA

UUCAGA-AGGUAU
AGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCAGGUAUCUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AGGAAA

905
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACGACA

UUCAGA-GUACAC
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUCGUACACCUAAUCAUC

loop-symmetric_

CUAUAG-ACGACA

906
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGUGGGCG

UUCAGA-AGCUCC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCAGCUCCCUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GUGGGC

907
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAUCGCG

UUCAGA-GGUACC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGUACCCUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CAUCGC

908
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGCCUUG

UUCAGA-GGGCUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGGGCUCCUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AGCCUU

909
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGAACACG

UUCAGA-AAGCUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAAGCUUCUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GAACAC

910
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGCGCGUG

UUCAGA-GCCUUC
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUCGCCUUCCUAAUCAUC

loop-symmetric_

UAUAGA-GCGCGU

911
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCUGGAGAG

UUCAGA-AAUUCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCAAUUCUCUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CUGGAG

912
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCAAACAG

UUCAGA-GUAUCU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGUAUCUCUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GCAAAC

913
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGUGCGAG

UUCAGA-AAACUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCAAACUUCUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GGUGCG

914
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGAGGAAA

UUCAGA-AGGCCU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCAGGCCUCUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GAGGAA

915
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCGGAAGAG

UUCAGA-AAACCC
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUCAAACCCCUAAUCAUC

loop-symmetric_

AUAGAA-CGGAAG

916
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGCGCCUAG

UUCAGA-GGCUUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGCUUUCUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AGCGCC

917
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAGUAUUA

UUCAGA-AACAUU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCAACAUUCUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAGUAU

918
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGAAUUUA

UUCAGA-AGCUUU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCAGCUUUCUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AGAAUU

919
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGUAGUUA

UUCAGA-AGAUCU
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUAUCAGAUCUCUAAUCAUC

loop-symmetric_

UAGAAG-AGUAGU

920
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGGCCACAUAG

UUCAGA-AAGUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAAGUCCCUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GGCCAC

921
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUAGUGAUA

UUCAGA-CACCGC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCCACCGCCUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AUAGUG

922
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGAGGACAUA

UUCAGA-GGUCAU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCGGUCAUCUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GAGGAC

923
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGGGCAAAUA

UUCAGA-AGGCAU
GGAUCCACAGGGAGGGGGCAUUUUAA

30_6-6_internal_
UAUAUCAGGCAUCUAAUCAUC

loop-symmetric_

AGAAGA-GGGCAA

924
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGACCAUAUAG

UUCAGA-CAAAUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCCAAAUCCUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGACCA

925
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCAUAAUAUAG

UUCAGA-AGUCGU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAGUCGUCUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCAUAA

926
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGAAUAUAUA

UUCAGA-GAUACC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCGAUACCCUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGAAUA

927
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUUAGCAUAUA

UUCAGA-GCCAUU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCGCCAUUCUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UUAGCA

928
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGACGGUAUAG

UUCAGA-GUGUUU
GAUCCACAGGGAGGGGGCAUUUUAAU

31_6-6_internal_
AUAUCGUGUUUCUAAUCAUC

loop-symmetric_

GAAGAU-CGACGG

929
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCUAGACUAUAG

UUCAGA-GGAAUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGAAUUCUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCUAGA

930
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUGGCCCUAUAG

UUCAGA-CAACAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCCAACACCUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUGGCC

931
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACGGACACUAUAG

UUCAGA-AGAUUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCAGAUUUCUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CGGACA

932
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCCAUACUAUAG

UUCAGA-CAACUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCCAACUUCUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCCAUA

933
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUCGGGCUAUAG

UUCAGA-AGGUUC
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAUCAGGUUCCUAAUCAUC

loop-symmetric_

AAGAUU-UUCGGG

934
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCCCUAUCUAUAG

UUCAGA-CACCUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCCACCUCCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCCCUA

935
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

936
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCGCUGUCUAUAG

UUCAGA-GUACUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGUACUCCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCGCUG

937
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUGCACUCUAUAG

UUCAGA-GGCUUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCGGCUUUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUGCAC

938
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCAGAAUCUAUAG

UUCAGA-AGUAAU
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUCAGUAAUCUAAUCAUC

loop-symmetric_

AGAUUU-CCAGAA

939
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUUUAUUCUAUA

UUCAGA-GAUACU
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUCGAUACUCUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AAUUUA

940
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUGCGUUCUAUA

UUCAGA-ACAUAC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCACAUACCUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUUGCG

941
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACCGCAUUCUAUAG

UUCAGA-AGGUGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAGGUGCCUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACCGCA

942
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAACGCAUUCUAUAG

UUCAGA-GCCCCC
GAUCCACAGGGAGGGGGCAUUUUAAU

34_6-6_internal_
AUAUCGCCCCCCUAAUCAUC

loop-symmetric_

GAUUUG-AACGCA

943
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUACCACCCUUCUAUAG

UUCAGA-AUAAGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCAUAAGCCUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-ACCACC

944
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAUGCCCUUCUAUAG

UUCAGA-GAAUUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGAAUUCCUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UAUGCC

945
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUGACCACUUCUAUAG

UUCAGA-AGCAUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCAGCAUCCUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UGACCA

946
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAGUGCCUUCUAUAG

UUCAGA-AGGUCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAGGUCCCUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UAGUGC

947
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUUUAUACUUCUAUA

UUCAGA-GGGUUC
GGAUCCACAGGGAGGGGGCAUUUUAA

35_6-6_internal_
UAUAUCGGGUUCCUAAUCAUC

loop-symmetric_

AUUUGC-UUUAUA

948
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACUUACCUCUUCUAUAG

UUCAGA-GGAUAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGAUAUCUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CUUACC

949
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACUAGUUUCUUCUAUAG

UUCAGA-AGCUAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAGCUAUCUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CUAGUU

950
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACAACCUUCUUCUAUAG

UUCAGA-GAGACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGAGACCCUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CAACCU

951
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAUCGCUCUUCUAUAG

UUCAGA-CACUCU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCCACUCUCUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAUCGC

952
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACAUUUUCUUCUAUAG

UUCAGA-AGCACU
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AUAUCAGCACUCUAAUCAUC

loop-symmetric_

UUUGCA-ACAUUU

953
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCCCUAUAUCUUCUAUAG

UUCAGA-GGUUUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGUUUCCUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CCCUAU

954
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUACUCUAUCUUCUAUAG

UUCAGA-GAGCCU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGAGCCUCUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UACUCU

955
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCACGUUAUCUUCUAUAG

UUCAGA-GUGCCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGUGCCCCUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CACGUU

956
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCACACUAUCUUCUAUAG

UUCAGA-GGGCCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCGGGCCCCUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CACACU

957
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCACUCCAUCUUCUAUAG

UUCAGA-AGGUUC
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUCAGGUUCCUAAUCAUC

loop-symmetric_

UUGCAU-CACUCC

958
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUGAACAAUCUUCUAUAG

UUCAGA-GACAGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGACAGCCUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUGAAC

959
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCGUCUAAUCUUCUAUAG

UUCAGA-GGUUAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGGUUAUCUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCGUCU

960
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCGACCAAUCUUCUAUAG

UUCAGA-GGAAUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCGGAAUCCUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCGACC

961
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCCAGUAAUCUUCUAUAG

UUCAGA-GCAUCC
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAUCGCAUCCCUAAUCAUC

loop-symmetric_

UGCAUC-CCCAGU

962
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCGCAGAAAUCUUCUAUAG

UUCAGA-GGGCAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGGCACCUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UCGCAG

963
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUUUUAAAAUCUUCUAUA

UUCAGA-GGAAGC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAAGCCUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUUUUA

964
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUAAAUAAAAUCUUCUAUA

UUCAGA-AGAUUC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCAGAUUCCUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UAAAUA

965
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUAUUUAAAAUCUUCUAUA

UUCAGA-AUACGU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUCAUACGUCUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UAUUUA

966
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACAUCCGAAAUCUUCUAUAG

UUCAGA-CACAGC
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUCCACAGCCUAAUCAUC

loop-symmetric_

GCAUCU-CAUCCG

967
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUGCUCCCAAAUCUUCUAUAG

UUCAGA-AUAAGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCAUAAGUCUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UGCUCC

968
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACUUUUUCAAAUCUUCUAUAG

UUCAGA-AUAUUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAUAUUUCUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CUUUUU

969
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCAACUCAAAUCUUCUAUAG

UUCAGA-GGAAUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGGAAUUCUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCAACU

970
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACUACACCAAAUCUUCUAUAG

UUCAGA-AAAAUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAAAAUUCUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CUACAC

971
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACAAAUCGCAAAUCUUCUAUAG

UUCAGA-CAUUUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCCAUUUUCUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CAAAUC

972
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACGCAAAGCAAAUCUUCUAUAG

UUCAGA-CACGCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCCACGCCCUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CGCAAA

973
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCACAAGCAAAUCUUCUAUAG

UUCAGA-GUCAAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGUCAAUCUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCACAA

974
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCGCUGGCAAAUCUUCUAUAG

UUCAGA-GUAUUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCGUAUUCCUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCGCUG

975
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACACUCAGCAAAUCUUCUAUAG

UUCAGA-GAUCUU
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUCGAUCUUCUAAUCAUC

loop-symmetric_

AUCUUU-CACUCA

976
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCGUCGUUGCAAAUCUUCUAUAG

UUCAGA-GUGUUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGUGUUUCUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CGUCGU

977
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUGUCCUGCAAAUCUUCUAUAG

UUCAGA-AGCAUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAGCAUCCUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUGUCC

978
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCGCUUCUGCAAAUCUUCUAUAG

UUCAGA-GGGUUC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCGGGUUCCUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CGCUUC

979
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUAACACUGCAAAUCUUCUAUAG

UUCAGA-AACUCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAACUCCCUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UAACAC

980
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUUACUUGCAAAUCUUCUAUAG

UUCAGA-GUGCUU
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUCGUGCUUCUAAUCAUC

loop-symmetric_

UCUUUU-UUUACU

981
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCAUCAUGCAAAUCUUCUAUAG

UUCAGA-AAAAAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAAAAACCUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCAUC

982
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUGUGAAUGCAAAUCUUCUAUA

UUCAGA-GUAUCU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUCGUAUCUCUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUGUGA

983
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUUACUAUGCAAAUCUUCUAUAG

UUCAGA-AAAACU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCAAAACUCUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUUACU

984
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCUUAAAUGCAAAUCUUCUAUAG

UUCAGA-AACACC
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUCAACACCCUAAUCAUC

loop-symmetric_

CUUUUG-GCUUAA

985
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUGGUCGAUGCAAAUCUUCUAUAG

UUCAGA-GGGCCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUCGGGCCUCUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUGGUC

986
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGAUCCGAUGCAAAUCUUCUAUAG

UUCAGA-AACAUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCAACAUCCUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGAUCC

987
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUGCUCGAUGCAAAUCUUCUAUAG

UUCAGA-CACACU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUCCACACUCUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUGCUC

988
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGUCCUGAUGCAAAUCUUCUAUAG

UUCAGA-GUAAGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUCGUAAGCCUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGUCCU

989
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGUAUCGAUGCAAAUCUUCUAUAG

UUCAGA-CAAUUU
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUCCAAUUUCUAAUCAUC

loop-symmetric_

UUUUGU-UGUAUC

990
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UCAGAG-GAAGCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGAAGCUACUAAUCAUC

A-C

991
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UCAGAG-GCAAAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGCAAAUACUAAUCAUC

A-C

992
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UCAGAG-AGGGCU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAGGGCUACUAAUCAUC

A-C

993
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UCAGAG-GCAUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGCAUACACUAAUCAUC

A-C

994
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

UCAGAG-AGAGAU
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAUAGAGAUACUAAUCAUC

995
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

UCAGAG-AGGCGU
CGCGAACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAGGCGUACUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UCGCGA

996
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAA

UCAGAG-GAGAAU
CCCUAACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAUGAGAAUACUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-ACCCUA

997
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAU

UCAGAG-AACCAC
CAGUAACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAACCACACUAAUCAUC

A-C

21_6-6_internal_

loop-symmetric_

GGAUCC-UCAGUA

998
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAC

UCAGAG-AGGUAU
UAGUAACAGGGAGGGGGCAUUUUAAU

21_6-6_internal_
AUAUAGGUAUACUAAUCAUC

loop-symmetric_

GGAUCC-CUAGUA

999
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCA

UCAGAG-GGAACC
CUGGCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGGAACCACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CACUGG

1000
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

UCAGAG-AUGCAC
ACAGCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAUGCACACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UAACAG

1001
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

UCAGAG-GGAAAU
AACACACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGGAAAUACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUAACA

1002
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

UCAGAG-AAGGCU
CUAACACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAAGGCUACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCCUAA

1003
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUA

UCAGAG-GAGAGU
GCAGCACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUAUGAGAGUACUAAUCAUC

loop-symmetric_

GAUCCU-UAGCAG

1004
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAACA

UCAGAG-GCAUUU
AUGCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGCAUUUACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-ACAAUG

1005
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUU

UCAGAG-GCAUAC
CGCCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUGCAUACACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CUUCGC

1006
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGUU

UCAGAG-AUAGUC
AAGCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAUAGUCACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GUUAAG

1007
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAUU

UCAGAG-AGAUAC
AAGCCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUAUAGAUACACUAAUCAUC

loop-symmetric_

AUCCUA-AUUAAG

1008
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUUUU

UCAGAG-GAGAGU
CUUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAUGAGAGUACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UUUUCU

1009
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUAUU

UCAGAG-AUAACU
GUUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAUAACUACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UAUUGU

1010
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGAC

UCAGAG-AAACCC
ACUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUAAACCCACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGACAC

1011
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCUUA

UCAGAG-GAACCU
UCUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUGAACCUACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CUUAUC

1012
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGUA

UCAGAG-AACCAC
CCUCCACAGGGAGGGGGCAUUUUAAUA

24_6-6_internal_
UAUAACCACACUAAUCAUC

loop-symmetric_

UCCUAU-UGUACC

1013
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACUUC

UCAGAG-AUUACC
AAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAUUACCACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACUUCA

1014
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCAGUC

UCAGAG-GAUACC
UAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGAUACCACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CAGUCU

1015
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCCCAC

UCAGAG-GGGACU
CAUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UAUGGGACUACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CCCACC

1016
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGACUC

UCAGAG-GCAUCC
CAUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAUGCAUCCACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GACUCC

1017
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACCGA

UCAGAG-GCAUAU
AAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAUGCAUAUACUAAUCAUC

loop-symmetric_

CCUAUA-ACCGAA

1018
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGUCUC

UCAGAG-GAACCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGAACCCACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AGUCUC

1019
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAAUCCU

UCAGAG-AACAAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAACAACACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AAUCCU

1020
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGCACC

UCAGAG-AGAGUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAGAGUUACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGCACC

1021
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGAUCAA

UCAGAG-AGACGU
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAUAGACGUACUAAUCAUC

loop-symmetric_

CUAUAG-GAUCAA

1022
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGACAAUG

UCAGAG-AACCAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAACCAUACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GACAAU

1023
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGCGCUG

UCAGAG-AACAUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAACAUUACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AGCGCU

1024
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCACGACG

UCAGAG-GCAGUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGCAGUUACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CACGAC

1025
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGUUUCCG

UCAGAG-GGAGCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGAGCCACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GUUUCC

1026
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGCUUUG

UCAGAG-ACGAGC
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAUACGAGCACUAAUCAUC

loop-symmetric_

UAUAGA-GGCUUU

1027
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGACAGAAG

UCAGAG-AAAGAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAAAGAUACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GACAGA

1028
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCUAGAGAG

UCAGAG-AUAAAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAUAAAUACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CUAGAG

1029
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCUGCGGAG

UCAGAG-AAGACU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAAGACUACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CUGCGG

1030
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCGAUCGAG

UCAGAG-GGUUAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGUUAUACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CGAUCG

1031
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAAGUUCAG

UCAGAG-AGAGCU
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAUAGAGCUACUAAUCAUC

loop-symmetric_

AUAGAA-AAGUUC

1032
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAAACCUAG

UCAGAG-ACGUAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUACGUACACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAAACC

1033
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGAGACUUA

UCAGAG-AAACCU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUAAACCUACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GAGACU

1034
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGAAUGCUA

UCAGAG-GCAUAU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUGCAUAUACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GAAUGC

1035
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGGCUUUUA

UCAGAG-AAACGC
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUAUAAACGCACUAAUCAUC

loop-symmetric_

UAGAAG-GGCUUU

1036
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACGAAUAAUA

UCAGAG-GAUAUC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUGAUAUCACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CGAAUA

1037
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGCAACAUAG

UCAGAG-GGACUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGGACUUACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGCAAC

1038
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGGCAUAAUA

UCAGAG-AAUUAU
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUAAUUAUACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GGCAUA

1039
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACACCGGAUAG

UCAGAG-GGAUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGAUACACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CACCGG

1040
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACGAGAAAUA

UCAGAG-GGGACC
GGAUCCACAGGGAGGGGGCAUUUUAA

30_6-6_internal_
UAUAUGGGACCACUAAUCAUC

loop-symmetric_

AGAAGA-CGAGAA

1041
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCUCAGUAUAG

UCAGAG-GAACAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGAACACACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCUCAG

1042
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCAGCGUAUAG

UCAGAG-GCAGAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGCAGAUACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCAGCG

1043
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGGAAAUAUA

UCAGAG-GGAAUC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAUGGAAUCACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGGAAA

1044
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUUGGGAUAUA

UCAGAG-GCAACU
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUGCAACUACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UUGGGA

1045
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGUGCAUAUAG

UCAGAG-AUGCAU
GAUCCACAGGGAGGGGGCAUUUUAAU

31_6-6_internal_
AUAUAUGCAUACUAAUCAUC

loop-symmetric_

GAAGAU-CGUGCA

1046
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUAAGCCUAUAG

UCAGAG-ACAAGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUACAAGUACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUAAGC

1047
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUAUAGCUAUA

UCAGAG-AUAGUC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUAUAGUCACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUAUAG

1048
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUAGGACUAUAG

UCAGAG-ACCAUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUACCAUUACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUAGGA

1049
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUAAGCCCUAUAG

UCAGAG-GCAUUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGCAUUUACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UAAGCC

1050
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCGCCGUCUAUAG

UCAGAG-AGUUAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAGUUACACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCGCCG

1051
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCGCCCCUCUAUAG

UCAGAG-AGAUAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAGAUACACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CGCCCC

1052
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCUUGGUCUAUAG

UCAGAG-AACAAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAACAACACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCUUGG

1053
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCCAUAUCUAUAG

UCAGAG-AGUAGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAGUAGCACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCCAUA

1054
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCUGGAUCUAUAG

UCAGAG-GAGAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUAUGAGAUCACUAAUCAUC

loop-symmetric_

AGAUUU-CCUGGA

1055
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUCCUAUUCUAUAG

UCAGAG-GACAUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGACAUCACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUCCUA

1056
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUCGCAUUCUAUAG

UCAGAG-AAGAUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAAGAUCACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUCGCA

1057
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCCUCGUUCUAUAG

UCAGAG-GGAGUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGGAGUUACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCCUCG

1058
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAUCGGGUUCUAUA

UCAGAG-ACGCAC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAUACGCACACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AUCGGG

1059
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUGGGUUCUAUA

UCAGAG-AUACCC
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUAUAUACCCACUAAUCAUC

loop-symmetric_

GAUUUG-GUUGGG

1060
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAAUUGACUUCUAUA

UCAGAG-ACAAGU
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAUACAAGUACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AAUUGA

1061
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAUUAGCUUCUAUA

UCAGAG-GAAAGU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUGAAAGUACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UAUUAG

1062
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUCGCCUUCUAUAG

UCAGAG-GAAGAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGAAGAUACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUUCGC

1063
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUGGUCCCUUCUAUAG

UCAGAG-GAAGAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGAAGAUACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UGGUCC

1064
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAGGUCGCUUCUAUAG

UCAGAG-AUGGCU
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUAUAUGGCUACUAAUCAUC

loop-symmetric_

AUUUGC-AGGUCG

1065
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCCCGUUCUUCUAUAG

UCAGAG-GGGGUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGGGGUCACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCCCGU

1066
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACUCCUCUCUUCUAUAG

UCAGAG-AAUUAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAAUUACACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CUCCUC

1067
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAGACUUCUUCUAUAG

UCAGAG-ACGUUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUACGUUUACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GAGACU

1068
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCUCGUUCUUCUAUAG

UCAGAG-GCACCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGCACCCACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCUCGU

1069
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAUUUCUCUUCUAUAG

UCAGAG-ACGGUU
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AUAUACGGUUACUAAUCAUC

loop-symmetric_

UUUGCA-GAUUUC

1070
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCAGGUAUCUUCUAUAG

UCAGAG-AGGACC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAGGACCACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCAGGU

1071
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGAUUCAUCUUCUAUAG

UCAGAG-AAGGUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAAGGUUACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CGAUUC

1072
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUCGUCAUCUUCUAUAG

UCAGAG-GGAGAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGGAGAUACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUCGUC

1073
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCCGUCAUCUUCUAUAG

UCAGAG-GAGCCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGAGCCCACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCCGUC

1074
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCCAUCUAUCUUCUAUAG

UCAGAG-ACCAUC
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUAUACCAUCACUAAUCAUC

loop-symmetric_

UUGCAU-CCAUCU

1075
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCUCGUAAUCUUCUAUAG

UCAGAG-GCAAUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGCAAUUACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCUCGU

1076
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAACCCAUAAUCUUCUAUAG

UCAGAG-AGAUAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAGAUAUACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-ACCCAU

1077
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUACUCAAUCUUCUAUAG

UCAGAG-AUACGU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAUACGUACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUACUC

1078
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAACGUUUAAUCUUCUAUAG

UCAGAG-GGAGAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGAGAUACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-ACGUUU

1079
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUCUAGAAAUCUUCUAUAG

UCAGAG-AAAUUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAAAUUUACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUCUAG

1080
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCAAAAAAAUCUUCUAUAG

UCAGAG-AAGGCC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAAGGCCACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UCAAAA

1081
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACGCCCAAAAUCUUCUAUAG

UCAGAG-AAGUUU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAAGUUUACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CGCCCA

1082
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACAUCAGAAAUCUUCUAUAG

UCAGAG-GAUCAC
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUAUGAUCACACUAAUCAUC

loop-symmetric_

GCAUCU-CAUCAG

1083
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCCAGUCAAAUCUUCUAUAG

UCAGAG-AGAGUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUAGAGUCACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCCAGU

1084
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCUGACCAAAUCUUCUAUAG

UCAGAG-AAGUCU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUAAGUCUACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCUGAC

1085
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUUACUUCAAAUCUUCUAUAG

UCAGAG-AUGCCU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAUGCCUACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UUACUU

1086
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUAACCAAAUCUUCUAUAG

UCAGAG-AAACCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUAAACCCACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCUAAC

1087
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCUUACCAAAUCUUCUAUAG

UCAGAG-GCAAUU
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAUGCAAUUACUAAUCAUC

loop-symmetric_

CAUCUU-UCUUAC

1088
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUGUCAGCAAAUCUUCUAUAG

UCAGAG-ACGAAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUACGAAUACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUGUCA

1089
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCCAUCGCAAAUCUUCUAUAG

UCAGAG-GGGGUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGGGGUCACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCCAUC

1090
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUGUCGGCAAAUCUUCUAUAG

UCAGAG-AGAAUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUAGAAUUACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUGUCG

1091
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUCCACAGCAAAUCUUCUAUAG

UCAGAG-GGAGCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGAGCCACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UCCACA

1092
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACGCAUGGCAAAUCUUCUAUAG

UCAGAG-AGAAAU
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUAUAGAAAUACUAAUCAUC

loop-symmetric_

AUCUUU-CGCAUG

1093
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCAUCUUGCAAAUCUUCUAUAG

UCAGAG-ACACAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUACACAUACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCAUCU

1094
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUUAACUGCAAAUCUUCUAUAG

UCAGAG-GACCAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGACCACACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UUUAAC

1095
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUCUAUUGCAAAUCUUCUAUAG

UCAGAG-GAUAUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGAUAUUACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUCUAU

1096
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGCCACUGCAAAUCUUCUAUAG

UCAGAG-GGACAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGACACACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UGCCAC

1097
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGCUUUUGCAAAUCUUCUAUAG

UCAGAG-AAUAUU
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAUAAUAUUACUAAUCAUC

loop-symmetric_

UCUUUU-UGCUUU

1098
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCACCCAUGCAAAUCUUCUAUAG

UCAGAG-GCGACC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGCGACCACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCACCC

1099
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGGUCUAUGCAAAUCUUCUAUAG

UCAGAG-GCGUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGCGUCCACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AGGUCU

1100
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUAUACAUGCAAAUCUUCUAUAG

UCAGAG-GCGUUU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAUGCGUUUACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUAUAC

1101
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCUAAAUGCAAAUCUUCUAUAG

UCAGAG-GGUUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGGUUACACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCUAA

1102
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUUGCCAUGCAAAUCUUCUAUAG

UCAGAG-AUACGC
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAUAUACGCACUAAUCAUC

loop-symmetric_

CUUUUG-GUUGCC

1103
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUACUCGAUGCAAAUCUUCUAUAG

UCAGAG-GCAGCU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAUGCAGCUACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUACUC

1104
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGCCCCGAUGCAAAUCUUCUAUAG

UCAGAG-GGGUCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUGGGUCCACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGCCCC

1105
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGCCUUGAUGCAAAUCUUCUAUAG

UCAGAG-GCGCAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAUGCGCAUACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGCCUU

1106
-5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUGGUUGAUGCAAAUCUUCUAUAG

UCAGAG-GGGCAC
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUAUGGGCACACUAAUCAUC

loop-symmetric_

UUUUGU-CUGGUU

1107
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

CAGAGA-GUAAGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGUAAGAAACUAAUCAUC

A-C

1108
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

CAGAGA-GCCCAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAGCCCAUAACUAAUCAUC

A-C

1109
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

CAGAGA-CGAGAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACGAGAUAACUAAUCAUC

A-C

1110
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

CAGAGA-AUGUAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAUGUACAACUAAUCAUC

A-C

1111
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

CAGAGA-AGAGAC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUAAGAGACAACUAAUCAUC

1112
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

CAGAGA-GUACGC
AUGACACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGUACGCAACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCAUGA

1113
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUU

CAGAGA-AGAGCC
UUGACACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAGAGCCAACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UUUUGA

1114
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

CAGAGA-AGCACC
AUGGCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAAGCACCAACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-CCAUGG

1115
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUUC

CAGAGA-AGCAGC
UUGGCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAGCAGCAACUAAUCAUC

A-C

22_6-6_internal_

loop-symmetric_

GAUCCU-UCUUGG

1116
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUCC

CAGAGA-CGAAAC
CCAGCACAGGGAGGGGGCAUUUUAAU

22_6-6_internal_
AUACGAAACAACUAAUCAUC

loop-symmetric_

GAUCCU-CCCCAG

1117
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACCU

CAGAGA-GUAAUC
UUCCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UAGUAAUCAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CCUUUC

1118
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACGA

CAGAGA-CAGAGA
AACCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UACAGAGAAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CGAAAC

1119
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUC

CAGAGA-AACGGA
GUACCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAAACGGAAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CUCGUA

1120
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAACA

CAGAGA-AGCAGU
ACACCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAAGCAGUAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-ACAACA

1121
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACUC

CAGAGA-GAGGUA
UCGCCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUAGAGGUAAACUAAUCAUC

loop-symmetric_

AUCCUA-CUCUCG

1122
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUACA

CAGAGA-GAGGUA
UUUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGAGGUAAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UACAUU

1123
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUAAU

CAGAGA-GCAGGA
CCUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UAGCAGGAAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UAAUCC

1124
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCAGA

CAGAGA-AACGUC
AUUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAAACGUCAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CAGAAU

1125
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCGU

CAGAGA-GGCGUU
UCUCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UAGGCGUUAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCGUUC

1126
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCCU

CAGAGA-AGGAGU
CUUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
AUAAGGAGUAACUAAUCAUC

loop-symmetric_

UCCUAU-CCCUCU

1127
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAGAUU

CAGAGA-CGGACA
CAUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UACGGACAAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AGAUUC

1128
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACUCC

CAGAGA-AGGAAU
UAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAGGAAUAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACUCCU

1129
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUCGA

CAGAGA-GUACGC
UAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGUACGCAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GUCGAU

1130
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACGUC

CAGAGA-AGGAGU
AAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAGGAGUAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACGUCA

1131
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCCACU

CAGAGA-GACAGC
CAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUAGACAGCAACUAAUCAUC

loop-symmetric_

CCUAUA-CCACUC

1132
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCUCCU

CAGAGA-GAAAAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGAAAAAAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCUCCU

1133
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAAUCGA

CAGAGA-CGGACC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUACGGACCAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AAUCGA

1134
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCGGUU

CAGAGA-GGUGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGGUGCAAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCGGUU

1135
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAAAAU

CAGAGA-AAGGGC
AGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAAAGGGCAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AAAAUA

1136
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGCCUC

CAGAGA-AGAAGA
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUAAGAAGAAACUAAUCAUC

loop-symmetric_

CUAUAG-GGCCUC

1137
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAUAACUG

CAGAGA-ACCACC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAACCACCAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AUAACU

1138
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAGCAUG

CAGAGA-CGCCAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUACGCCACAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CAGCAU

1139
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGACGGCG

CAGAGA-CACAUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACACAUAAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GACGGC

1140
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGCGAUG

CAGAGA-GUAGAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGUAGACAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AGCGAU

1141
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGAGUCCG

CAGAGA-AUGGGU
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUAAUGGGUAACUAAUCAUC

loop-symmetric_

UAUAGA-GAGUCC

1142
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCGACGAG

CAGAGA-GGAGUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGGAGUCAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GCGACG

1143
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCAGGGAG

CAGAGA-AGCACC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAGCACCAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CCAGGG

1144
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAACAAGAG

CAGAGA-AUGACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAAUGACCAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AACAAG

1145
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGUACCGAG

CAGAGA-GAGUAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGAGUAUAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GUACCG

1146
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGUCAGAG

CAGAGA-GGCCGC
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUAGGCCGCAACUAAUCAUC

loop-symmetric_

AUAGAA-GGUCAG

1147
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCAUCCUAG

CAGAGA-CGGGUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUACGGGUCAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCAUCC

1148
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAGAUUCUA

CAGAGA-AAAAGU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAAAAAGUAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AGAUUC

1149
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGAGGCCUAG

CAGAGA-CGGAAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACGGAAUAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GAGGCC

1150
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAAAGUUA

CAGAGA-GGGAGC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAGGGAGCAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAAAGU

1151
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGACAGUUA

CAGAGA-GACGUC
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUAGACGUCAACUAAUCAUC

loop-symmetric_

UAGAAG-GACAGU

1152
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAACGGAUAG

CAGAGA-AUGGGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAAUGGGAAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAACGG

1153
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAACCGAAUAG

CAGAGA-CCAGGU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUACCAGGUAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AACCGA

1154
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAACGACAUAG

CAGAGA-GAAACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGAAACCAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AACGAC

1155
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUGCACAUAG

CAGAGA-AUAUAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAUAUAAAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AUGCAC

1156
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGGCCGGAUAG

CAGAGA-AGCAGA
GAUCCACAGGGAGGGGGCAUUUUAAU

30_6-6_internal_
AUAAGCAGAAACUAAUCAUC

loop-symmetric_

AGAAGA-GGCCGG

1157
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGAAAGUAUA

CAGAGA-GCCGCA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUAGCCGCAAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGAAAG

1158
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUAAUGGUAUA

CAGAGA-GCACAU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAGCACAUAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UAAUGG

1159
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACACAUAUAUAG

CAGAGA-AGCAAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAAGCAAUAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CACAUA

1160
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUUGCUAUAUA

CAGAGA-GAAGAC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUAGAAGACAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UUGCUA

1161
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAAUUAUAUA

CAGAGA-GGCGCC
GGAUCCACAGGGAGGGGGCAUUUUAA

31_6-6_internal_
UAUAGGCGCCAACUAAUCAUC

loop-symmetric_

GAAGAU-CAAUUA

1162
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCGAGCCUAUAG

CAGAGA-AAGGUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAAAGGUUAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCGAGC

1163
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCCAGCCUAUAG

CAGAGA-AUGAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAUGAGAAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CCCAGC

1164
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUCACACUAUAG

CAGAGA-GGUGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGGUGCAAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUCACA

1165
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUGGGCCUAUAG

CAGAGA-GGCACC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGGCACCAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CUGGGC

1166
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACCCGGACUAUAG

CAGAGA-AUACAC
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
AUAAUACACAACUAAUCAUC

loop-symmetric_

AAGAUU-CCCGGA

1167
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCAGGCUCUAUAG

CAGAGA-AAAGCC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAAAAGCCAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCAGGC

1168
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCGCGGAUCUAUAG

CAGAGA-GUAGUC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAGUAGUCAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CGCGGA

1169
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUGGCGUCUAUAG

CAGAGA-CGAAAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACGAAAUAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGGCG

1170
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUGCGGUCUAUAG

CAGAGA-AGGGAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAGGGAAAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGCGG

1171
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCCGAAUCUAUAG

CAGAGA-CCCAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUACCCAAAAACUAAUCAUC

loop-symmetric_

AGAUUU-CCCGAA

1172
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACGCCGUUCUAUAG

CAGAGA-GAGGAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGAGGAUAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACGCCG

1173
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUACGUUCUAUA

CAGAGA-AGCGUU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAAGCGUUAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AAUACG

1174
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUCAGUUCUAUA

CAGAGA-AUGGGA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUAAUGGGAAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUUCAG

1175
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUACCAUUCUAUAG

CAGAGA-GGAGCC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGGAGCCAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUACCA

1176
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUGAGUUCUAUA

CAGAGA-GACGGC
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUAGACGGCAACUAAUCAUC

loop-symmetric_

GAUUUG-GUUGAG

1177
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAACUCACUUCUAUAG

CAGAGA-GAGUAU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGAGUAUAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AACUCA

1178
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUGACCACUUCUAUAG

CAGAGA-AACCGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAACCGCAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UGACCA

1179
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUACGCUUCUAUAG

CAGAGA-CGCACA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACGCACAAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUUACG

1180
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUUACCACUUCUAUAG

CAGAGA-CGGACA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUACGGACAAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UUACCA

1181
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUCCACCUUCUAUAG

CAGAGA-AACACC
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUAAACACCAACUAAUCAUC

loop-symmetric_

AUUUGC-CUCCAC

1182
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAGGCUUCUUCUAUAG

CAGAGA-CAGGAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUACAGGACAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GAGGCU

1183
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGAAUCCUCUUCUAUAG

CAGAGA-AUGGCC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAUGGCCAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GAAUCC

1184
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAGUCCUCUUCUAUAG

CAGAGA-GCAGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGCAGCAAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAGUCC

1185
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGACCUCUCUUCUAUAG

CAGAGA-AAGGUC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAAGGUCAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GACCUC

1186
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAAUACAUCUUCUAUAG

CAGAGA-GCGGUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGCGGUCAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CAAUAC

1187
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAUAUCAUCUUCUAUAG

CAGAGA-AACAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAACAGAAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CAUAUC

1188
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUAGAUAUCUUCUAUAG

CAGAGA-CACCCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACACCCAAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUAGAU

1189
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCAGUUAUCUUCUAUAG

CAGAGA-AUAGAU
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAAUAGAUAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCAGUU

1190
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUAGGUAUCUUCUAUAG

CAGAGA-CGAGCC
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUACGAGCCAACUAAUCAUC

loop-symmetric_

UUGCAU-CUAGGU

1191
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCCAAUAAUCUUCUAUAG

CAGAGA-GUAUUC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGUAUUCAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCCAAU

1192
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACGGACCAAUCUUCUAUAG

CAGAGA-CCAAAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUACCAAACAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CGGACC

1193
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCCCCUAAUCUUCUAUAG

CAGAGA-CGGGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACGGGCAAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CCCCCU

1194
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCGUUUAAUCUUCUAUAG

CAGAGA-CGGUAU

5_1-1_mismatch_
GAUCCACAGGGAGGGGGCAUCUUAAU

A-C
AUACGGUAUAACUAAUCAUC

38_6-6_internal_

loop-symmetric_

UGCAUC-CCGUUU

1195
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACAACCUAAUCUUCUAUAG

CAGAGA-AUAGAC
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUAAUAGACAACUAAUCAUC

loop-symmetric_

UGCAUC-CAACCU

1196
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCCCCGAAAUCUUCUAUAG

CAGAGA-AGCACA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAAGCACAAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CCCCCG

1197
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCGCAGAAAUCUUCUAUAG

CAGAGA-AAAGUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAAAGUAAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CCGCAG

1198
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCCAAAAAAUCUUCUAUAG

CAGAGA-GCCGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGCCGCAAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CCCAAA

1199
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACCACAAAAAUCUUCUAUAG

CAGAGA-GAACGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGAACGCAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CCACAA

1200
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUUGAGAAAUCUUCUAUA

CAGAGA-GCAACC
GGAUCCACAGGGAGGGGGCAUUUUAA

39_6-6_internal_
UAUAGCAACCAACUAAUCAUC

loop-symmetric_

GCAUCU-UUUGAG

1201
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUAAUCAAAUCUUCUAUAG

CAGAGA-GAAGUU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGAAGUUAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCUAAU

1202
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACACGCUCAAAUCUUCUAUAG

CAGAGA-AGAGAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAAGAGAAAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CACGCU

1203
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACACGCCCAAAUCUUCUAUAG

CAGAGA-CCAGAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUACCAGACAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CACGCC

1204
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACAUAGCCAAAUCUUCUAUAG

CAGAGA-CGGUAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUACGGUAAAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CAUAGC

1205
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACUACUCCAAAUCUUCUAUAG

CAGAGA-GUGGCC
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUAGUGGCCAACUAAUCAUC

loop-symmetric_

CAUCUU-CUACUC

1206
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCAUUCGCAAAUCUUCUAUAG

CAGAGA-GGGAGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGGGAGUAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCAUUC

1207
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUGUACGGCAAAUCUUCUAUAG

CAGAGA-CAGGGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUACAGGGCAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UGUACG

1208
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUAAUGGCAAAUCUUCUAUAG

CAGAGA-GAGACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGAGACCAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUAAUG

1209
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCAUAGGCAAAUCUUCUAUAG

CAGAGA-GGAGAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGGAGACAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCAUAG

1210
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUGCCAGCAAAUCUUCUAUAG

CAGAGA-CAACGC
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUACAACGCAACUAAUCAUC

loop-symmetric_

AUCUUU-CUGCCA

1211
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCCCUCUGCAAAUCUUCUAUAG

CAGAGA-ACAGGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAACAGGCAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCCCUC

1212
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCGUCCUGCAAAUCUUCUAUAG

CAGAGA-GACAUU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAGACAUUAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCGUCC

1213
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUACACUGCAAAUCUUCUAUAG

CAGAGA-GGGAGU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGGGAGUAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUACAC

1214
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCUUACUGCAAAUCUUCUAUAG

CAGAGA-GCCACA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGCCACAAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCUUAC

1215
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUCUCUUGCAAAUCUUCUAUAG

CAGAGA-GUAGCA
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUAGUAGCAAACUAAUCAUC

loop-symmetric_

UCUUUU-CUCUCU

1216
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUAACCAUGCAAAUCUUCUAUAG

CAGAGA-GUAGGU
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAGUAGGUAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUAACC

1217
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAACUUAAUGCAAAUCUUCUAUAG

CAGAGA-GUGGAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAGUGGAAAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AACUUA

1218
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACUCAUAUGCAAAUCUUCUAUAG

CAGAGA-AGGACC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAAGGACCAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-ACUCAU

1219
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCUAUCAUGCAAAUCUUCUAUAG

CAGAGA-GAAGGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUAGAAGGAAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCUAUC

1220
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGUGCUAUGCAAAUCUUCUAUAG

CAGAGA-GGGAGC
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUAGGGAGCAACUAAUCAUC

loop-symmetric_

CUUUUG-AGUGCU

1221
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUCUUCGAUGCAAAUCUUCUAUAG

CAGAGA-AACACA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUAAACACAAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUCUUC

1222
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUGGCCGAUGCAAAUCUUCUAUAG

CAGAGA-GCCCAU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAGCCCAUAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUGGCC

1223
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUGGUCCGAUGCAAAUCUUCUAUAG

CAGAGA-GCACAU
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUAGCACAUAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UGGUCC

1224
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUUAUGAUGCAAAUCUUCUAUAG

CAGAGA-CAGAUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUACAGAUAAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUUUAU

1225
-4_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUGUUGAUGCAAAUCUUCUAUAG

CAGAGA-CCCAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUACCCAAAAACUAAUCAUC

loop-symmetric_

UUUUGU-CUUGUU

1226
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAGAU-UGGCGC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUGGCGCGAACUAAUCAUC

A-C

1227
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAGAU-UGUACC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUGUACCGAACUAAUCAUC

A-C

1228
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAGAU-UCAGAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUCAGAGGAACUAAUCAUC

A-C

1229
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAGAU-CGGCAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCGGCAAGAACUAAUCAUC

A-C

1230
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAGAU-UGGCCC
GAUCCACAGGGAGGGGGCAUUUUAAU

AUUGGCCCGAACUAAUCAUC

1231
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAAGC

AGAGAU-UGGGGG
CUACCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UUGGGGGGAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-AGCCUA

1232
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAACU

AGAGAU-CAGAAG
CACCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UCAGAAGGAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-ACUCAC

1233
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUACCC

AGAGAU-UCAUAC
ACACCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
UUCAUACGAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-CCCACA

1234
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGCC

AGAGAU-UCACCC
GCGCCACAGGGAGGGGGCAUCUUAAUA

5_1-1_mismatch_
UUCACCCGAACUAAUCAUC

A-C

23_6-6_internal_

loop-symmetric_

AUCCUA-GCCGCG

1235
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAGAA

AGAGAU-UGUGGC
AUGCCACAGGGAGGGGGCAUUUUAAU

23_6-6_internal_
AUUGUGGCGAACUAAUCAUC

loop-symmetric_

AUCCUA-GAAAUG

1236
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCUU

AGAGAU-UAGAAA
CUUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UUAGAAAGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCUUCU

1237
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUAUA

AGAGAU-UACCAG
CCUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
UUACCAGGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UAUACC

1238
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUUUA

AGAGAU-CAUGGA
UUUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCAUGGAGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UUUAUU

1239
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUGCA

AGAGAU-UUGGGG
AUUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUUGGGGGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UGCAAU

1240
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCGAGU

AGAGAU-UGAGGG
CAUCCACAGGGAGGGGGCAUUUUAACA

0_1-1_mismatch_
UUGAGGGGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CGAGUC

1241
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCUCGU

AGAGAU-CGGAAG
UAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCGGAAGGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CUCGUU

1242
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACAAA

AGAGAU-UUGGAA
UAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUUGGAAGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACAAAU

1243
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAGAAU

AGAGAU-CCUACG
AAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCCUACGGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AGAAUA

1244
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACAAC

AGAGAU-UAAGUA
UAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
AUUAAGUAGAACUAAUCAUC

loop-symmetric_

CCUAUA-ACAACU

1245
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAACCAC

AGAGAU-CAUAUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCAUAUAGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AACCAC

1246
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAAGGCA

AGAGAU-UAGUAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUAGUACGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AAGGCA

1247
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGCCCGA

AGAGAU-UAAAGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUAAAGGGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GCCCGA

1248
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAUCUUA

AGAGAU-UCCAUA
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AUUCCAUAGAACUAAUCAUC

loop-symmetric_

CUAUAG-AUCUUA

1249
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCCCCCCG

AGAGAU-UAAAUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUAAAUGGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CCCCCC

1250
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGGACUG

AGAGAU-UUGGGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUUGGGCGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGGACU

1251
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGUAUUU

AGAGAU-UUAAGA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUUUAAGAGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GUAUUU

1252
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCCACCCG

AGAGAU-UUGGUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUUGGUAGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-CCACCC

1253
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGCACCG

AGAGAU-CCGCAA
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
AUCCGCAAGAACUAAUCAUC

loop-symmetric_

UAUAGA-AGCACC

1254
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAUACCGAG

AGAGAU-UCCAGG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUCCAGGGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AUACCG

1255
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGAAUCAAG

AGAGAU-UAGCGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUAGCGCGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GAAUCA

1256
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGGUCACAG

AGAGAU-CCACCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCCACCAGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GGUCAC

1257
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCAUCAGAG

AGAGAU-UUUAGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUUUAGGGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-CAUCAG

1258
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCGACGGAG

AGAGAU-UCAGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AUUCAGGGGAACUAAUCAUC

loop-symmetric_

AUAGAA-CGACGG

1259
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUUAGCUA

AGAGAU-UAACAA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUUAACAAGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AUUAGC

1260
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAGAGUUA

AGAGAU-CCGAAC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUCCGAACGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAGAGU

1261
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCCACCUAG

AGAGAU-UAGGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUAGGGAGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCCACC

1262
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAUACUUA

AGAGAU-UAGCGA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUUAGCGAGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAUACU

1263
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGACGUUUA

AGAGAU-CAAGGA
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UAUCAAGGAGAACUAAUCAUC

loop-symmetric_

UAGAAG-GACGUU

1264
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACAUAUGAUA

AGAGAU-UUAAUA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUUUAAUAGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CAUAUG

1265
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGUCAAAUA

AGAGAU-CCUGCG
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUCCUGCGGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGUCAA

1266
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACCCCGCAUAG

AGAGAU-CCGAGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCCGAGAGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CCCCGC

1267
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACACGAAAUAG

AGAGAU-CAAGUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCAAGUAGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CACGAA

1268
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGCCAGAAUAG

AGAGAU-CGAGUG
GAUCCACAGGGAGGGGGCAUUUUAAU

30_6-6_internal_
AUCGAGUGGAACUAAUCAUC

loop-symmetric_

AGAAGA-GCCAGA

1269
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUGGGGAUAUA

AGAGAU-UGGCGA
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUUGGCGAGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UGGGGA

1270
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACUGGUAUAUA

AGAGAU-UAACGC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUUAACGCGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CUGGUA

1271
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGGGAAUAUA

AGAGAU-CCACCA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUCCACCAGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGGGAA

1272
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUCAACGUAUAG

AGAGAU-UUGAGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUUGAGAGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UCAACG

1273
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUGACCCUAUAG

AGAGAU-UAGCCG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUAGCCGGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUGACC

1274
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUAAAACCUAUAG

AGAGAU-CGUAUG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCGUAUGGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UAAAAC

1275
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUCAUGCUAUAG

AGAGAU-UAAACA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUAAACAGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUCAUG

1276
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUGCAGCCUAUAG

AGAGAU-UGUAUG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUGUAUGGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UGCAGC

1277
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUAGGGCUAUA

AGAGAU-UCAGGA
GGAUCCACAGGGAGGGGGCAUUUUAA

32_6-6_internal_
UAUUCAGGAGAACUAAUCAUC

loop-symmetric_

AAGAUU-UUAGGG

1278
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCCUACUCUAUAG

AGAGAU-UGUAGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUGUAGAGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCCUAC

1279
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUACAAUCUAUAG

AGAGAU-CCUGCG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCCUGCGGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUACAA

1280
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCGGGCUCUAUAG

AGAGAU-UGACCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUGACCGGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCGGGC

1281
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCAACCUCUAUAG

AGAGAU-CAAUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AUCAAUGGGAACUAAUCAUC

loop-symmetric_

AGAUUU-CCAACC

1282
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUUAGUUCUAUA

AGAGAU-UGGCGG
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUUGGCGGGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUUUAG

1283
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGACUGCGUUCUAUAG

AGAGAU-UCAGAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUCAGAAGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-ACUGCG

1284
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAUACGGUUCUAUA

AGAGAU-UUGAAA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAUUUGAAAGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AUACGG

1285
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCGUGAUUCUAUA

AGAGAU-CCAAUG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUCCAAUGGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCGUGA

1286
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGUAAAUUCUAUA

AGAGAU-CGAACG
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAUCGAACGGAACUAAUCAUC

loop-symmetric_

GAUUUG-AGUAAA

1287
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAAUAUACUUCUAUA

AGAGAU-UAGGAC
GGAUCCACAGGGAGGGGGCAUUUUAA

0_1-1_mismatch_
CAUUAGGACGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AAUAUA

1288
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUCGCCUUCUAUAG

AGAGAU-CAUAGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCAUAGGGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUUCGC

1289
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUCCGCCUUCUAUAG

AGAGAU-CAGCGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCAGCGAGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUCCGC

1290
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAUUGUGCUUCUAUA

AGAGAU-UCACAG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUUCACAGGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AUUGUG

1291
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUACACCUUCUAUAG

AGAGAU-CAGGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
AUCAGGAGGAACUAAUCAUC

loop-symmetric_

AUUUGC-CUACAC

1292
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGUCUACUCUUCUAUAG

AGAGAU-UAAGUA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUAAGUAGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GUCUAC

1293
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGGGUCCUCUUCUAUAG

AGAGAU-CCAGGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCCAGGGGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-GGGUCC

1294
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCCCUCUCUUCUAUAG

AGAGAU-UCAAAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUCAAACGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCCCUC

1295
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACAUUCUCUUCUAUAG

AGAGAU-CACAGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCACAGCGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-ACAUUC

1296
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAAACCUCUUCUAUAG

AGAGAU-UGGAUG
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AUUGGAUGGAACUAAUCAUC

loop-symmetric_

UUUGCA-AAAACC

1297
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCCGUUAUCUUCUAUAG

AGAGAU-UACAAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUACAACGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCCGUU

1298
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUACUUCAUCUUCUAUAG

AGAGAU-UGGCAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUGGCACGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UACUUC

1299
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAAAUUAUCUUCUAUAG

AGAGAU-UGGGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUGGGGAGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CAAAUU

1300
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUAAGAUAUCUUCUAUA

AGAGAU-CCAGUG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUCCAGUGGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UAAGAU

1301
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCGUUUUAUCUUCUAUAG

AGAGAU-UAGUAC
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AUUAGUACGAACUAAUCAUC

loop-symmetric_

UUGCAU-CGUUUU

1302
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUAUUCAAUCUUCUAUAG

AGAGAU-UAACGA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUAACGAGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UUAUUC

1303
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUCUCCAAUCUUCUAUAG

AGAGAU-CAAGGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCAAGGGGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AUCUCC

1304
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACUAUCUAAUCUUCUAUAG

AGAGAU-UUGGAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUUGGACGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CUAUCU

1305
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCUAGUAAUCUUCUAUAG

AGAGAU-UUGAGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUUUGAGAGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CCUAGU

1306
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACAACGUAAUCUUCUAUAG

AGAGAU-CGAGAA
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
AUCGAGAAGAACUAAUCAUC

loop-symmetric_

UGCAUC-CAACGU

1307
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACGCAAAAAAUCUUCUAUAG

AGAGAU-UGUAAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUGUAACGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CGCAAA

1308
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUAUCAGAAAUCUUCUAUAG

AGAGAU-CGAGAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCGAGACGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UAUCAG

1309
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACACUAGAAAUCUUCUAUAG

AGAGAU-CCGAGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCCGAGCGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CACUAG

1310
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUAUUAAAAUCUUCUAUA

AGAGAU-UGGGUG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAUUGGGUGGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUAUUA

1311
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCAACGAAAUCUUCUAUAG

AGAGAU-CCAAGC
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
AUCCAAGCGAACUAAUCAUC

loop-symmetric_

GCAUCU-UCAACG

1312
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUCACCCCAAAUCUUCUAUAG

AGAGAU-UAGACG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUAGACGGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UCACCC

1313
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUAAUCAAAUCUUCUAUAG

AGAGAU-CGACGC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCGACGCGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCUAAU

1314
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACUCCAUCAAAUCUUCUAUAG

AGAGAU-CGACCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCGACCAGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CUCCAU

1315
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACAAUUUCAAAUCUUCUAUAG

AGAGAU-CAGCAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCAGCAAGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CAAUUU

1316
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCUGCCCAAAUCUUCUAUAG

AGAGAU-UCCAGA
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AUUCCAGAGAACUAAUCAUC

loop-symmetric_

CAUCUU-CCUGCC

1317
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCGUGCGCAAAUCUUCUAUAG

AGAGAU-UACAAC
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUACAACGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCGUGC

1318
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUAUACGCAAAUCUUCUAUAG

AGAGAU-UUACGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUUACGGGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUAUAC

1319
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUAACCGCAAAUCUUCUAUAG

AGAGAU-UAGCAC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUAGCACGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CUAACC

1320
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUUGUAGCAAAUCUUCUAUAG

AGAGAU-CAAGGC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCAAGGCGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUUGUA

1321
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUGCUCAGCAAAUCUUCUAUAG

AGAGAU-CAGUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
AUCAGUGGGAACUAAUCAUC

loop-symmetric_

AUCUUU-UGCUCA

1322
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCCUAUUGCAAAUCUUCUAUAG

AGAGAU-UUAGUG
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUUAGUGGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCCUAU

1323
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUGUACCUGCAAAUCUUCUAUAG

AGAGAU-CAGCAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCAGCAGGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UGUACC

1324
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCCCUCUGCAAAUCUUCUAUAG

AGAGAU-UCCAAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUCCAAAGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UCCCUC

1325
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUCCGUUGCAAAUCUUCUAUAG

AGAGAU-CCGCAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCCGCAAGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UUCCGU

1326
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCGGCCUUGCAAAUCUUCUAUAG

AGAGAU-CAAGGA
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AUCAAGGAGAACUAAUCAUC

loop-symmetric_

UCUUUU-CGGCCU

1327
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUGGCAAUGCAAAUCUUCUAUAG

AGAGAU-UAACAA
GAUCCACAGGGAGGGGGCAUUUUAAC

0_1-1_mismatch_
AUUAACAAGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AUGGCA

1328
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAAUCAAAUGCAAAUCUUCUAUAG

AGAGAU-UUGGAC
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUUUGGACGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AAUCAA

1329
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCCAUAAUGCAAAUCUUCUAUAG

AGAGAU-UACCGC
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUUACCGCGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCCAUA

1330
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUCAAAAUGCAAAUCUUCUAUAG

AGAGAU-CGAGGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCGAGGAGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUCAAA

1331
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUCCUCAUGCAAAUCUUCUAUAG

AGAGAU-CAUGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
AUCAUGAGGAACUAAUCAUC

loop-symmetric_

CUUUUG-AUCCUC

1332
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUCAUGAUGCAAAUCUUCUAUAG

AGAGAU-CCGGGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUCCGGGAGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAUCAU

1333
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUACCCUGAUGCAAAUCUUCUAUAG

AGAGAU-CACCAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AUCACCAGGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UACCCU

1334
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUGUCUGAUGCAAAUCUUCUAUAG

AGAGAU-CGUAUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AUCGUAUAGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUGUCU

1335
-3_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUGGUUGAUGCAAAUCUUCUAUAG

AGAGAU-CACACG
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
AUCACACGGAACUAAUCAUC

loop-symmetric_

UUUUGU-CUGGUU

1336
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAGAUA-AUGACG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAUGACGUGAACUAAUCAUC

A-C

1337
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAGAUA-AUGAGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AAUGAGGUGAACUAAUCAUC

A-C

1338
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAGAUA-AUGAAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AAUGAAAUGAACUAAUCAUC

A-C

1339
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

GAGAUA-AACGCA
GAUCCACAGGGAGGGGGCAUUUUAAU

AAACGCAUGAACUAAUCAUC

1340
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCUA

GAGAUA-GCCACG
CCUCCACAGGGAGGGGGCAUUUCAAUA

3_1-1_mismatch_
GCCACGUGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCUACC

1341
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCCCC

GAGAUA-ACCACA
ACUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
ACCACAUGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-CCCCAC

1342
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUUCCA

GAGAUA-ACCAGG
UUUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AACCAGGUGAACUAAUCAUC

A-C

24_6-6_internal_

loop-symmetric_

UCCUAU-UCCAUU

1343
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUCGCU

GAGAUA-CUGGAA
UCUCCACAGGGAGGGGGCAUUUUAAU

24_6-6_internal_
ACUGGAAUGAACUAAUCAUC

loop-symmetric_

UCCUAU-CGCUUC

1344
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGAUCC

GAGAUA-AACAAG
UAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAACAAGUGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GAUCCU

1345
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGCAGU

GAGAUA-CCAGCA
CAUCCACAGGGAGGGGGCAUUCUAAUA

4_1-1_mismatch_
CCAGCAUGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-GCAGUC

1346
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCAACAU

GAGAUA-GCGAAG
AAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AGCGAAGUGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-AACAUA

1347
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGUAAA

GAGAUA-CGGGGG
AAUCCACAGGGAGGGGGCAUUUUAAU

25_6-6_internal_
ACGGGGGUGAACUAAUCAUC

loop-symmetric_

CCUAUA-GUAAAA

1348
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGAUAA

GAGAUA-GUAUAA
UGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAGUAUAAUGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GAUAAU

1349
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGUCUU

GAGAUA-ACGACA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AACGACAUGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AGUCUU

1350
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGCGCU

GAGAUA-GCAAUA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AGCAAUAUGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGCGCU

1351
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGCACU

GAGAUA-GGAUAG
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
AGGAUAGUGAACUAAUCAUC

loop-symmetric_

CUAUAG-GGCACU

1352
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAUACUCG

GAGAUA-AAAGUA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAAAGUAUGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-AUACUC

1353
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGAGCGUG

GAGAUA-GUGGAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGUGGAAUGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GAGCGU

1354
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGUUCGCG

GAGAUA-CAAUGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACAAUGGUGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GUUCGC

1355
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAACAUUG

GAGAUA-CCCGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
ACCCGAGUGAACUAAUCAUC

loop-symmetric_

UAUAGA-AACAUU

1356
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCACAAAG

GAGAUA-GGGACA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGGGACAUGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GCACAA

1357
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAAGUUCAG

GAGAUA-GUAGAA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AGUAGAAUGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AAGUUC

1358
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCGACAAAG

GAGAUA-GGGUUA
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
AGGGUUAUGAACUAAUCAUC

loop-symmetric_

AUAGAA-CGACAA

1359
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUGUAUUA

GAGAUA-GCUACA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAGCUACAUGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AUGUAU

1360
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGAGGCCUAG

GAGAUA-AGCUAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AAGCUAGUGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GAGGCC

1361
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAAUGGCUA

GAGAUA-CCAUAA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UACCAUAAUGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-AAUGGC

1362
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUACAAGUUA

GAGAUA-CGCGAG
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UACGCGAGUGAACUAAUCAUC

loop-symmetric_

UAGAAG-ACAAGU

1363
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAAGCGAAUA

GAGAUA-CAGGUA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UACAGGUAUGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AAGCGA

1364
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGUAUUGAUA

GAGAUA-GUGUGG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAGUGUGGUGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GUAUUG

1365
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGGUACAUA

GAGAUA-CAGAGA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UACAGAGAUGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AGGUAC

1366
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACGCCACAUAG

GAGAUA-GAAUGA
GAUCCACAGGGAGGGGGCAUUUUAAU

30_6-6_internal_
AGAAUGAUGAACUAAUCAUC

loop-symmetric_

AGAAGA-CGCCAC

1367
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACCGCAAUAUAG

GAGAUA-ACUACA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AACUACAUGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CCGCAA

1368
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAAACGUAUAG

GAGAUA-CACGCG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
ACACGCGUGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAAACG

1369
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACUGCGGUAUAG

GAGAUA-CCCGGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACCCGGGUGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CUGCGG

1370
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACACACAUAUAG

GAGAUA-GCGGGA
GAUCCACAGGGAGGGGGCAUUUUAAU

31_6-6_internal_
AGCGGGAUGAACUAAUCAUC

loop-symmetric_

GAAGAU-CACACA

1371
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUAGGGCUAUA

GAGAUA-AUGAGG
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAAUGAGGUGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUAGGG

1372
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUGGUACCUAUAG

GAGAUA-GCCAAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGCCAAAUGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UGGUAC

1373
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCAAAACUAUAG

GAGAUA-CGAAAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACGAAAGUGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UCAAAA

1374
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACGACCCCUAUAG

GAGAUA-CGAGGG
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
ACGAGGGUGAACUAAUCAUC

loop-symmetric_

AAGAUU-CGACCC

1375
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCGCAAAUCUAUAG

GAGAUA-GUGGCA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AGUGGCAUGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CGCAAA

1376
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCCGGAGUCUAUAG

GAGAUA-GACCAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGACCAAUGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CCGGAG

1377
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCAAAAUCUAUAG

GAGAUA-GGGGCA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AGGGGCAUGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UCAAAA

1378
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUACAUAUCUAUAG

GAGAUA-GUAGCG
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
AGUAGCGUGAACUAAUCAUC

loop-symmetric_

AGAUUU-UACAUA

1379
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCCUAGUUCUAUAG

GAGAUA-ACCCAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AACCCAAUGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCCUAG

1380
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUUGAUUCUAUA

GAGAUA-AAAGUA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAAAAGUAUGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUUUGA

1381
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGUUACAUUCUAUA

GAGAUA-ACAGCA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UAACAGCAUGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GUUACA

1382
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAUCAAUUCUAUA

GAGAUA-ACCACG
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UAACCACGUGAACUAAUCAUC

loop-symmetric_

GAUUUG-AAUCAA

1383
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUCCGUCCUUCUAUAG

GAGAUA-AUGACA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAUGACAUGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UCCGUC

1384
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAAGUGGCUUCUAUA

GAGAUA-GCAAAA
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UAGCAAAAUGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AAGUGG

1385
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUAACGUCCUUCUAUAG

GAGAUA-ACUGAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AACUGAGUGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-AACGUC

1386
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUCACCUUCUAUAG

GAGAUA-CGGUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
ACGGUGGUGAACUAAUCAUC

loop-symmetric_

AUUUGC-CUUCAC

1387
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCGUUUUCUUCUAUAG

GAGAUA-CGGAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
ACGGAGAUGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCGUUU

1388
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACUAGUCUCUUCUAUAG

GAGAUA-GCUGGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGCUGGGUGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CUAGUC

1389
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAACACUUUCUUCUAUAG

GAGAUA-GUGGGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AGUGGGAUGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-ACACUU

1390
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGACCUUUCUUCUAUAG

GAGAUA-GAAUAA
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
AGAAUAAUGAACUAAUCAUC

loop-symmetric_

UUUGCA-GACCUU

1391
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCACCCUAUCUUCUAUAG

GAGAUA-GCGGAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AGCGGAGUGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CACCCU

1392
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCAUUUAUCUUCUAUAG

GAGAUA-CCCUAG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
ACCCUAGUGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCAUUU

1393
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUUACCCAUCUUCUAUAG

GAGAUA-GGCAGA
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
AGGCAGAUGAACUAAUCAUC

loop-symmetric_

UUGCAU-UUACCC

1394
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUUUUUCAAUCUUCUAUAG

GAGAUA-ACGAAA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AACGAAAUGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UUUUUC

1395
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCAUAUAAUCUUCUAUAG

GAGAUA-AAGUGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AAAGUGGUGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-UCAUAU

1396
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUUAACAAUCUUCUAUAG

GAGAUA-CAAUAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACAAUAGUGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AUUAAC

1397
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAACAAUAAUCUUCUAUAG

GAGAUA-CUGAGG
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
ACUGAGGUGAACUAAUCAUC

loop-symmetric_

UGCAUC-AACAAU

1398
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUACACAAAAUCUUCUAUAG

GAGAUA-GCCGCA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AGCCGCAUGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UACACA

1399
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUCCCGAAAUCUUCUAUAG

GAGAUA-GAAGAA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGAAGAAUGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UUCCCG

1400
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACGCACGAAAUCUUCUAUAG

GAGAUA-ACAGCG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AACAGCGUGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CGCACG

1401
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUGAAUUCAAAUCUUCUAUAG

GAGAUA-AAAAGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAAAAGGUGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UGAAUU

1402
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACGCUUUCAAAUCUUCUAUAG

GAGAUA-CUAGCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
ACUAGCAUGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CGCUUU

1403
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUGAAUACAAAUCUUCUAUAG

GAGAUA-GACUGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AGACUGAUGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UGAAUA

1404
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUUAUUUCAAAUCUUCUAUAG

GAGAUA-GUGAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
AGUGAAAUGAACUAAUCAUC

loop-symmetric_

CAUCUU-UUAUUU

1405
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACCUAGCGCAAAUCUUCUAUAG

GAGAUA-GUGUGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AGUGUGGUGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CCUAGC

1406
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUUCUAGCAAAUCUUCUAUAG

GAGAUA-CGAGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
ACGAGGAUGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UUUCUA

1407
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACGCAACGCAAAUCUUCUAUAG

GAGAUA-CCGACA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACCGACAUGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CGCAAC

1408
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUUCGGGCAAAUCUUCUAUAG

GAGAUA-CUAGAG
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
ACUAGAGUGAACUAAUCAUC

loop-symmetric_

AUCUUU-CUUCGG

1409
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCGCACUUGCAAAUCUUCUAUAG

GAGAUA-CUGGGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
ACUGGGGUGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CGCACU

1410
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCCUACUGCAAAUCUUCUAUAG

GAGAUA-GGAGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AGGAGGAUGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCCUAC

1411
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCCUCCCUGCAAAUCUUCUAUAG

GAGAUA-AGCGGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
AAGCGGGUGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CCUCCC

1412
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUUCCCUGCAAAUCUUCUAUAG

GAGAUA-GAAUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
AGAAUGGUGAACUAAUCAUC

loop-symmetric_

UCUUUU-CUUCCC

1413
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACUUCCAUGCAAAUCUUCUAUAG

GAGAUA-AGGAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAGGAGAUGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-ACUUCC

1414
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCACCAAUGCAAAUCUUCUAUAG

GAGAUA-CGGGUA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
ACGGGUAUGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCACCA

1415
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAACCCAUAUGCAAAUCUUCUAUAG

GAGAUA-CAAGAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACAAGAGUGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-ACCCAU

1416
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCUCUCAUGCAAAUCUUCUAUAG

GAGAUA-CAGGCA
GAUCCACAGGGAGGGGGCAUUUUAAU

43_6-6_internal_
ACAGGCAUGAACUAAUCAUC

loop-symmetric_

CUUUUG-GCUCUC

1417
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUCUUUGAUGCAAAUCUUCUAUAG

GAGAUA-AGGGGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AAGGGGAUGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUCUUU

1418
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUCCACUGAUGCAAAUCUUCUAUAG

GAGAUA-ACAACG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
AACAACGUGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UCCACU

1419
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUUACGAUGCAAAUCUUCUAUAG

GAGAUA-CACCCA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
ACACCCAUGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-CUUUAC

1420
-2_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAUAUCGAUGCAAAUCUUCUAUAG

GAGAUA-CACUGA
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
ACACUGAUGAACUAAUCAUC

loop-symmetric_

UUUUGU-UAUAUC

1421
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAACC

CCCUGGA
CUGGACUGAACUAAUCAUC

1422
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAUAU-CCCAAG
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
CCAAGCUGAACUAAUCAUC

A-C

1423
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAUAU-UCGCGG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UCGCGGCUGAACUAAUCAUC

A-C

1424
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAUAU-CCUGGA
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
CUGGACUGAACUAAUCAUC

A-C

1425
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCUAUAG

AGAUAU-UACUGA
GAUCCACAGGGAGGGGGCAUUUUAAU

UACUGACUGAACUAAUCAUC

1426
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACUUU

AGAUAUA-
CAUCCACAGGGAGGGGGCAUUUUAACC

CCCCUUG
CCUUGCUGAACUAAUCAUC

25_6-6_internal_

loop-symmetric_

CCUAUA-ACUUUC

1427
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCUCCC

AGAUAU-CGGACG
UAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
GGACGCUGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CUCCCU

1428
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCACAUA

AGAUAU-UCUGAC
UAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UCUGACCUGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-ACAUAU

1429
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCCAAUC

AGAUAU-UAACAC
UAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UAACACCUGAACUAAUCAUC

A-C

25_6-6_internal_

loop-symmetric_

CCUAUA-CAAUCU

1430
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUCGGCGC

AGAUAU-CGCCGA
CAUCCACAGGGAGGGGGCAUUUUAAUC

25_6-6_internal_
GCCGACUGAACUAAUCAUC

loop-symmetric_

CCUAUA-GGCGCC

1431
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGAGCUU

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUUUAGG
UUUAGGCUGAACUAAUCAUC

26_6-6_internal_

loop-symmetric_

CUAUAG-GAGCUU

1432
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGGUCAU

AGAUAU-CUGACA
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
UGACACUGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-GGUCAU

1433
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUAGCUCC

AGAUAU-UACGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UACGGACUGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-AGCUCC

1434
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUACGAUU

AGAUAU-CCGGAC
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
CGGACCUGAACUAAUCAUC

A-C

26_6-6_internal_

loop-symmetric_

CUAUAG-ACGAUU

1435
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUUGACGCC

AGAUAU-CGGCAG
GAUCCACAGGGAGGGGGCAUUUUAAU

26_6-6_internal_
CGGCAGCUGAACUAAUCAUC

loop-symmetric_

CUAUAG-GACGCC

1436
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUAGCCCUG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CGAGCGG
GAGCGGCUGAACUAAUCAUC

27_6-6_internal_

loop-symmetric_

UAUAGA-AGCCCU

1437
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGAUUGCG

AGAUAU-UUUAGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UUUAGGCUGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GAUUGC

1438
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGACCUG

AGAUAU-CGCUAG
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
GCUAGCUGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGACCU

1439
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUGGUUACG

AGAUAU-UCCGGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UCCGGACUGAACUAAUCAUC

A-C

27_6-6_internal_

loop-symmetric_

UAUAGA-GGUUAC

1440
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCUCAGUCUG

AGAUAU-CAAACA
GAUCCACAGGGAGGGGGCAUUUUAAU

27_6-6_internal_
CAAACACUGAACUAAUCAUC

loop-symmetric_

UAUAGA-CAGUCU

1441
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCCAUGAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUACCAC
UACCACCUGAACUAAUCAUC

28_6-6_internal_

loop-symmetric_

AUAGAA-GCCAUG

1442
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGCCAUGAG

AGAUAU-UACUGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UACUGGCUGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GCCAUG

1443
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCGUAGGAA

AGAUAU-CUUGAC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UCUUGACCUGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-GUAGGA

1444
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCAAGAACAG

AGAUAU-UUUGAG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UUUGAGCUGAACUAAUCAUC

A-C

28_6-6_internal_

loop-symmetric_

AUAGAA-AAGAAC

1445
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUCCCGGGAAG

AGAUAU-CGGCGA
GAUCCACAGGGAGGGGGCAUUUUAAU

28_6-6_internal_
CGGCGACUGAACUAAUCAUC

loop-symmetric_

AUAGAA-CCGGGA

1446
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCAGAUUA

AGAUAUA-
GGAUCCACAGGGAGGGGGCAUUUUAA

CCACCGA
CCACCGACUGAACUAAUCAUC

29_6-6_internal_

loop-symmetric_

UAGAAG-GCAGAU

1447
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUGCAGUCUAG

AGAUAU-UGGCAG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UGGCAGCUGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-GCAGUC

1448
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUACAACCUAG

AGAUAU-UAAAGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UAAAGACUGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-ACAACC

1449
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUACAGAUUA

AGAUAU-UCAAAC
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UUCAAACCUGAACUAAUCAUC

A-C

29_6-6_internal_

loop-symmetric_

UAGAAG-ACAGAU

1450
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAUAUAGGUUA

AGAUAU-UCGAGG
GGAUCCACAGGGAGGGGGCAUUUUAA

29_6-6_internal_
UUCGAGGCUGAACUAAUCAUC

loop-symmetric_

UAGAAG-AUAGGU

1451
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAACCCCAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAACC

CCCUCAG
CUCAGCUGAACUAAUCAUC

30_6-6_internal_

loop-symmetric_

AGAAGA-AACCCC

1452
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAGUCAAAAUA

AGAUAU-CCAGAC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UCCAGACCUGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-GUCAAA

1453
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAUUAAAAUA

AGAUAU-CAACGG
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UCAACGGCUGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-AUUAAA

1454
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAACCCGUAAUAG

AGAUAU-CACGAC
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
ACGACCUGAACUAAUCAUC

A-C

30_6-6_internal_

loop-symmetric_

AGAAGA-CCCGUA

1455
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAAAGAUAAAUA

AGAUAU-UCAGAC
GGAUCCACAGGGAGGGGGCAUUUUAA

30_6-6_internal_
UUCAGACCUGAACUAAUCAUC

loop-symmetric_

AGAAGA-AGAUAA

1456
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGACAAUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CACUUAA
ACUUAACUGAACUAAUCAUC

31_6-6_internal_

loop-symmetric_

GAAGAU-CGACAA

1457
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACGUUAAUAUA

AGAUAU-CCAAAC
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UCCAAACCUGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CGUUAA

1458
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAGUGGUAUA

AGAUAU-UGCGAC
GGAUCCACAGGGAGGGGGCAUUCUAA

4_1-1_mismatch_
UUGCGACCUGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-CAGUGG

1459
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAAUAGGGAUAUA

AGAUAU-CAUUAA
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UCAUUAACUGAACUAAUCAUC

A-C

31_6-6_internal_

loop-symmetric_

GAAGAU-UAGGGA

1460
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAACAGGAGUAUA

AGAUAU-UGCCAA
GGAUCCACAGGGAGGGGGCAUUUUAA

31_6-6_internal_
UUGCCAACUGAACUAAUCAUC

loop-symmetric_

GAAGAU-CAGGAG

1461
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACUGGGCCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CAACCGG
AACCGGCUGAACUAAUCAUC

32_6-6_internal_

loop-symmetric_

AAGAUU-CUGGGC

1462
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUACGGGCUAUAG

AGAUAU-UGUGGG
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UGUGGGCUGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UACGGG

1463
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCACAGGGGCUAUAG

AGAUAU-UCCCUG
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UCCCUGCUGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-CAGGGG

1464
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUUGAGACUAUA

AGAUAU-UGGGAG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UUGGGAGCUGAACUAAUCAUC

A-C

32_6-6_internal_

loop-symmetric_

AAGAUU-UUGAGA

1465
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCAUCGGCCCUAUAG

AGAUAU-CAUUAC
GAUCCACAGGGAGGGGGCAUUUUAAU

32_6-6_internal_
CAUUACCUGAACUAAUCAUC

loop-symmetric_

AAGAUU-UCGGCC

1466
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUCAAGGUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUACCGG
UACCGGCUGAACUAAUCAUC

33_6-6_internal_

loop-symmetric_

AGAUUU-UCAAGG

1467
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUUCACUCUAUAG

AGAUAU-UUUGGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UUUGGACUGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUUCAC

1468
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCUUUGGCUCUAUAG

AGAUAU-CUUGGA
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
UUGGACUGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-UUUGGC

1469
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCUCAGAUCUAUAG

AGAUAU-CCAGGG
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
CAGGGCUGAACUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUCAGA

1470
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGCCAUAAAUCUAUAG

AGAUAU-CACUAG
GAUCCACAGGGAGGGGGCAUUUUAAU

33_6-6_internal_
CACUAGCUGAACUAAUCAUC

loop-symmetric_

AGAUUU-CAUAAA

1471
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAGCCAGUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUUUGUG
UUUGUGCUGAACUAAUCAUC

34_6-6_internal_

loop-symmetric_

GAUUUG-AGCCAG

1472
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAAACUAUUCUAUA

AGAUAU-CAGGUG
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UCAGGUGCUGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-AAACUA

1473
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCUCAAUUCUAUAG

AGAUAU-CACUGA
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
ACUGACUGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCUCAA

1474
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGGCGCCAUUCUAUAG

AGAUAU-CACAAA
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
ACAAACUGAACUAAUCAUC

A-C

34_6-6_internal_

loop-symmetric_

GAUUUG-GCGCCA

1475
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUGAUUCGGUUCUAUA

AGAUAU-UCUGGG
GGAUCCACAGGGAGGGGGCAUUUUAA

34_6-6_internal_
UUCUGGGCUGAACUAAUCAUC

loop-symmetric_

GAUUUG-AUUCGG

1476
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUACUGACUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CGAGCGG
GAGCGGCUGAACUAAUCAUC

35_6-6_internal_

loop-symmetric_

AUUUGC-UACUGA

1477
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUUAAUAACUUCUAUA

AGAUAU-UACCAA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UUACCAACUGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-UAAUAA

1478
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUCACCUUCUAUAG

AGAUAU-UGCCCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UGCCCACUGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUUCAC

1479
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUGCCCUUCUAUAG

AGAUAU-UACCGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UACCGGCUGAACUAAUCAUC

A-C

35_6-6_internal_

loop-symmetric_

AUUUGC-CUUGCC

1480
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAUCUUUACCUUCUAUAG

AGAUAU-CGAAAA
GAUCCACAGGGAGGGGGCAUUUUAAU

35_6-6_internal_
CGAAAACUGAACUAAUCAUC

loop-symmetric_

AUUUGC-CUUUAC

1481
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACAGUUCUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CACUUGG
ACUUGGCUGAACUAAUCAUC

36_6-6_internal_

loop-symmetric_

UUUGCA-CAGUUC

1482
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACAAUCUUCUUCUAUAG

AGAUAU-UGGCGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UGGCGACUGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CAAUCU

1483
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGACCCCCUUCUUCUAUAG

AGAUAU-CGUUAA
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
GUUAACUGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-CCCCCU

1484
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAAAGGUUUCUUCUAUA

AGAUAU-UGUGGG
GGAUCCACAGGGAGGGGGCAUCUUAA

5_1-1_mismatch_
UUGUGGGCUGAACUAAUCAUC

A-C

36_6-6_internal_

loop-symmetric_

UUUGCA-AAGGUU

1485
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGAGACCACUCUUCUAUAG

AGAUAU-UUUAAG
GAUCCACAGGGAGGGGGCAUUUUAAU

36_6-6_internal_
UUUAAGCUGAACUAAUCAUC

loop-symmetric_

UUUGCA-GACCAC

1486
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCCAGAUAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUGCUAG
UGCUAGCUGAACUAAUCAUC

37_6-6_internal_

loop-symmetric_

UUGCAU-CCAGAU

1487
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCUUUUAUCUUCUAUAG

AGAUAU-UGCAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UGCAGACUGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCUUUU

1488
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCUUUCUAUCUUCUAUAG

AGAUAU-CGACGG
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
GACGGCUGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-CUUUCU

1489
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGUCAUCUAUCUUCUAUAG

AGAUAU-UAUAGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UAUAGGCUGAACUAAUCAUC

A-C

37_6-6_internal_

loop-symmetric_

UUGCAU-UCAUCU

1490
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAGCAUAGUAUCUUCUAUAG

AGAUAU-CACCUG
GAUCCACAGGGAGGGGGCAUUUUAAU

37_6-6_internal_
CACCUGCUGAACUAAUCAUC

loop-symmetric_

UUGCAU-CAUAGU

1491
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACAGAAUAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUCUAAG
UCUAAGCUGAACUAAUCAUC

38_6-6_internal_

loop-symmetric_

UGCAUC-CAGAAU

1492
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAAUUUACAAUCUUCUAUAG

AGAUAU-UCGAGA
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
UCGAGACUGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-AUUUAC

1493
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAACCUAUCAAUCUUCUAUAG

AGAUAU-CUCCGG
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
UCCGGCUGAACUAAUCAUC

A-C

38_6-6_internal_

loop-symmetric_

UGCAUC-CCUAUC

1494
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAAUCUCCCAAUCUUCUAUAG

AGAUAU-UGGACG
GAUCCACAGGGAGGGGGCAUUUUAAU

38_6-6_internal_
UGGACGCUGAACUAAUCAUC

loop-symmetric_

UGCAUC-UCUCCC

1495
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUCUAAAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAACC

CCGUUAA
GUUAACUGAACUAAUCAUC

39_6-6_internal_

loop-symmetric_

GCAUCU-UUCUAA

1496
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAACUCUAAAAAUCUUCUAUAG

AGAUAU-CAUUGG
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
AUUGGCUGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-CUCUAA

1497
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUACGAGAAAUCUUCUAUAG

AGAUAU-UGACCA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UGACCACUGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UACGAG

1498
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUCCGGAAAAUCUUCUAUAG

AGAUAU-UCGGGG
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UCGGGGCUGAACUAAUCAUC

A-C

39_6-6_internal_

loop-symmetric_

GCAUCU-UCCGGA

1499
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAAUUAACAAAAUCUUCUAUAG

AGAUAU-UCCUGG
GAUCCACAGGGAGGGGGCAUUUUAAU

39_6-6_internal_
UCCUGGCUGAACUAAUCAUC

loop-symmetric_

GCAUCU-UUAACA

1500
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUAUAGCCAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CACAGGA
ACAGGACUGAACUAAUCAUC

40_6-6_internal_

loop-symmetric_

CAUCUU-UAUAGC

1501
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUGCAGCCAAAUCUUCUAUAG

AGAUAU-CAGGUA
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
AGGUACUGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UGCAGC

1502
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACCACAACAAAUCUUCUAUAG

AGAUAU-UAGGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UAGGGACUGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-CCACAA

1503
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAAUUUACUCAAAUCUUCUAUAG

AGAUAU-CUCCGA
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
UCCGACUGAACUAAUCAUC

A-C

40_6-6_internal_

loop-symmetric_

CAUCUU-UUUACU

1504
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAACACUUACAAAUCUUCUAUAG

AGAUAU-UCCAUG
GAUCCACAGGGAGGGGGCAUUUUAAU

40_6-6_internal_
UCCAUGCUGAACUAAUCAUC

loop-symmetric_

CAUCUU-CACUUA

1505
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUAUGCGGCAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAACC

CCUUAGA
UUAGACUGAACUAAUCAUC

41_6-6_internal_

loop-symmetric_

AUCUUU-UAUGCG

1506
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUACAAAGCAAAUCUUCUAUAG

AGAUAU-CCCUGA
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
CCUGACUGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-UACAAA

1507
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACUUAACGCAAAUCUUCUAUAG

AGAUAU-CCAGGG
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
CAGGGCUGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CUUAAC

1508
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACACGCCCGGCAAAUCUUCUAUAG

AGAUAU-CACCAG
GAUCCACAGGGAGGGGGCAUCUUAAUC

5_1-1_mismatch_
ACCAGCUGAACUAAUCAUC

A-C

41_6-6_internal_

loop-symmetric_

AUCUUU-CGCCCG

1509
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACAUUUUCCGCAAAUCUUCUAUAG

AGAUAU-CGAGUA
GAUCCACAGGGAGGGGGCAUUUUAAU

41_6-6_internal_
CGAGUACUGAACUAAUCAUC

loop-symmetric_

AUCUUU-UUUUCC

1510
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUCACUUGCAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAACC

CCCUCCA
CUCCACUGAACUAAUCAUC

42_6-6_internal_

loop-symmetric_

UCUUUU-UUCACU

1511
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUUCGCUUGCAAAUCUUCUAUAG

AGAUAU-CGUUAC
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
GUUACCUGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UUCGCU

1512
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUAUAACUGCAAAUCUUCUAUAG

AGAUAU-UCUGGA
GAUCCACAGGGAGGGGGCAUUCUAAU

4_1-1_mismatch_
UCUGGACUGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-UAUAAC

1513
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACCUUGUCUGCAAAUCUUCUAUAG

AGAUAU-UAGGGA
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UAGGGACUGAACUAAUCAUC

A-C

42_6-6_internal_

loop-symmetric_

UCUUUU-CUUGUC

1514
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACACUCUCGUUGCAAAUCUUCUAUAG

AGAUAU-UAAGUG
GAUCCACAGGGAGGGGGCAUUUUAAU

42_6-6_internal_
UAAGUGCUGAACUAAUCAUC

loop-symmetric_

UCUUUU-UCUCGU

1515
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUGCUAAUGCAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CACGCGG
ACGCGGCUGAACUAAUCAUC

43_6-6_internal_

loop-symmetric_

CUUUUG-GUGCUA

1516
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAGCUAUAUGCAAAUCUUCUAUAG

AGAUAU-CCAAAC
GAUCCACAGGGAGGGGGCAUUUCAAUC

3_1-1_mismatch_
CAAACCUGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-AGCUAU

1517
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGCCCCCAUGCAAAUCUUCUAUAG

AGAUAU-CCGACG
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
CGACGCUGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GCCCCC

1518
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAGUGCUCAUGCAAAUCUUCUAUAG

AGAUAU-UGAAAC
GAUCCACAGGGAGGGGGCAUCUUAAU

5_1-1_mismatch_
UGAAACCUGAACUAAUCAUC

A-C

43_6-6_internal_

loop-symmetric_

CUUUUG-GUGCUC

1519
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACAAUUUGUAUGCAAAUCUUCUAUA

AGAUAU-CCUAGA
GGAUCCACAGGGAGGGGGCAUUUUAA

43_6-6_internal_
UCCUAGACUGAACUAAUCAUC

loop-symmetric_

CUUUUG-AUUUGU

1520
-6->0_7-7_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUUACUGAUGCAAAUCUUCUAUAG

AGAUAUA-
GAUCCACAGGGAGGGGGCAUUUUAAC

CUCUUAA
UCUUAACUGAACUAAUCAUC

44_6-6_internal_

loop-symmetric_

UUUUGU-UUUACU

1521
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUUUAGUGAUGCAAAUCUUCUAUA

AGAUAU-UGCGUA
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UUGCGUACUGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UUUAGU

1522
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACUAGCUCGAUGCAAAUCUUCUAUAG

AGAUAU-CUUUAC
GAUCCACAGGGAGGGGGCAUUCUAAUC

4_1-1_mismatch_
UUUACCUGAACUAAUCAUC

A-C

44_6-6_internal_

loop-symmetric_

UUUUGU-UAGCUC

1523
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGCACUCAU

loop-symmetric_
CACCUUUCCGAUGCAAAUCUUCUAUAG

AGAUAU-UUUAGA
GAUCCACAGGGAGGGGGCAUUUUAAU

44_6-6_internal_
UUUAGACUGAACUAAUCAUC

loop-symmetric_

UUUUGU-CUUUCC

1524
-11_2-2_bulge-
GAUAUUGUGAAUUAUCUCUGGCCUCA

symmetric_
UCACUAAAAAGAUGACAAUCUUCUUA

GU-UG
AGGAUCCAACGGGAGGGGAGAUUUUA

-1_2-2_bulge-
AUCCAUCUCUGAUGUAAUCAUC

symmetric_

AU-CC

8_2-2_bulge-

symmetric_

GC-AG

18_2-2_bulge-

symmetric_

UG-AC

28_2-2_bulge-

symmetric_

AU-UA

38_2-2_bulge-

symmetric_

UG-AC

48_2-2_bulge-

symmetric_

GU-UA

58_2-2_bulge-

symmetric_

UG-GC

68_2-2_bulge-

symmetric_

UG-AU

1525
-10_3-3_bulge-
GAUAUUGUGACAACGCUCUGCACGAUU

symmetric_
CACACAACAAAUGCAAAUAUGCUAUAG

GUU-CCG
GAAGAACAGGGAGAAAGCAUUUUAUU

-1->1_3-3_bulge-
UUAUCUCUGCCGUAAUCAUC

symmetric_

UAU-UUU

10_3-3_bulge-

symmetric_

CCC-AAA

21_3-3_bulge-

symmetric_

GGA-AGA

32_3-3_bulge-

symmetric_

AAG-AUG

43_3-3_bulge-

symmetric_

CUU-CAA

54_3-3_bulge-

symmetric_

UGA-GAU

65_3-3_bulge-

symmetric_

AUA-ACG

1526
-9_4-4_bulge-
GAUAAUACGACAUAUCGAACCACUCAU

symmetric_
CUAUGAAAAGAUGAACCUCUUCUAUCA

GUUC-CUUG

0->3_4-4_bulge-

symmetric_

AUUA-CUUC

12_4-4_bulge-

symmetric_

CCUC-CCUU

24_4-4_bulge-
CCUCCACAGGCCUUGGGCAUUUCUUCA

symmetric_
UAUCUCUCUUGUAAUCAUC

UCCU-CACC

36_4-4_bulge-

symmetric_

UUUG-AACC

48_4-4_bulge-

symmetric_

GUGU-UAUG

60_4-4_bulge-

symmetric_

CAGA-GAAC

72_4-4_bulge-

symmetric_

ACAA-AUAC

1527
-8_5-5_internal_
GAUAUUGUGCGAAUUCUCUGCAGAUU

loop-symmetric_
CCACACAAACAAGCCAAAUCUUGAUUC

GUUCA-AUUCG
GGAUCCACCACAUGGGGGCAUACUUCU

1_5-5_internal_
AUAUCUCAUUCGUAAUCAUC

loop-symmetric_

UUAAA-ACUUC

14_5-5_internal_

loop-symmetric_

UCCCU-CACAU

27_5-5_internal_

loop-symmetric_

UAUAG-GAUUC

40_5-5_internal_

loop-symmetric_

CAUCU-CAAGC

53_5-5_internal_

loop-symmetric_

AUGAG-GAUUC

66_5-5_internal_

loop-symmetric_

UAUGU-CGAAU

1528
-7_6-6_internal_
GACCUGGGGACAUAUCGAGAGUCUCAU

loop-symmetric_
CACCUCUAUGAUGCAAAACACGGAUAG

GUUCAG-AUAAUG
GAUCAUCUCAGAGGGGGCUUUAACAU

2_6-6_internal_
AUAUCUAUAAUGUAAUCAUC

loop-symmetric_

UAAAAU-UUUAAC

16_6-6_internal_

loop-symmetric_

CCUGUG-AUCUCA

30_6-6_internal_

loop-symmetric_

AGAAGA-ACACGG

44_6-6_internal_

loop-symmetric_

UUUUGU-CUCUAU

58_6-6_internal_

loop-symmetric_

UGCAGA-GAGAGU

72_6-6_internal_

loop-symmetric_

ACAAUA-CCUGGG

1529
-6_7-7_internal_
GAUAUUGUGAAGCUGGACUGCACUCCA

loop-symmetric_
AAGUGAAAAGAUGGUACUACUCUAUA

GUUCAGA-
GGUAAUUGUGGGAGGGGAUAAUACAA

GGUCAUG
UAUAUCGGUCAUGUAAUCAUC

3_7-7_internal_

loop-symmetric_

AAAAUGC-

AUAAUAC

18_7-7_internal_

loop-symmetric_

UGUGGAU-

UAAUUGU

33_7-7_internal_

loop-symmetric_

AGAUUUG-

GUACUAC

48_7-7_internal_

loop-symmetric_

GUGUGAU-

CAAAGUG

63_7-7_internal_

loop-symmetric_

AGAUAUG-

AGCUGGA

1530
-5_8-8_internal_
GAUACUAUUAAUUAUCUCUGGUGGAU

loop-symmetric_
GGACACAAAAACUCCGUCUCUUCUAUC

GUUCAGAG-
UAAUAGUCAGGGAGGCGAUUUAGUAA

GCGUCCAA
UAUAUGCGUCCAAUAAUCAUC

4_8-8_internal_

loop-symmetric_

AAAUGCCC-

CGAUUUAG

20_8-8_internal_

loop-symmetric_

UGGAUCCU-

CUAAUAGU

36_8-8_internal_

loop-symmetric_

UUUGCAUC-

ACUCCGUC

52_8-8_internal_

loop-symmetric_

GAUGAGUG-

GUGGAUGG

68_8-8_internal_

loop-symmetric_

UGUCACAA-

CUAUUAAU

1531
-9_2-2_bulge-
GAUACGGUGACAUAUCCGUGCACUCAU

symmetric_
CCAACAAAAGAUGGUAAUCUUCUAUUC

UC-AC
GAUCCACAGGUUGGGGGCAUUUGUAU

2_2-2_bulge-
AUAUCUCUACACUAAUCAUC

symmetric_

UA-GU

14_2-2_bulge-

symmetric_

UC-UU

26_2-2_bulge-

symmetric_

CU-UC

38_2-2_bulge-

symmetric_

UG-GU

50_2-2_bulge-

symmetric_

GU-CA

62_2-2_bulge-

symmetric_

GA-CG

74_2-2_bulge-

symmetric_

AA-CG

1532
-8_3-3_bulge-
GAUAUUGUGUGUUAUCUCUGCAGAAA

symmetric_
UCACACAAACCUUGCAAAUCUUAGCUA

UCA-AAU
GGAUCCACUAUGAGGGGGCAUACCAAU

3_3-3_bulge-
AUAUCUCAAUACUAAUCAUC

symmetric_

AAA-ACC

16_3-3_bulge-

symmetric_

CCU-UAU

29_3-3_bulge-

symmetric_

UAG-AGC

42_3-3_bulge-

symmetric_

UCU-CCU

55_3-3_bulge-

symmetric_

GAG-GAA

68_3-3_bulge-

symmetric_

UGU-UGU

1533
-7_4-4_bulge-
GAGUACGUGACAUAUCCACCCACUCAU

symmetric_
CACCUCCAAGAUGCAAAGUAACUAUAG

UCAG-GAUC
GAUCAUCUGGGAGGGGGCUGAAUAAU

4_4-4_bulge-
AUAUCUGAUCACUAAUCAUC

symmetric_

AAAU-UGAA

18_4-4_bulge-

symmetric_

UGUG-AUCU

32_4-4_bulge-

symmetric_

AAGA-GUAA

46_4-4_bulge-

symmetric_

UUGU-CUCC

60_4-4_bulge-

symmetric_

CAGA-CACC

74_4-4_bulge-

symmetric_

AAUA-GUAC

1534
-6_5-5_internal_
GAUAUUGUGAGUACACUCUGCACUCCC

loop-symmetric_
AAAACAAAAGAUGGUCACCUUCUAUA

UCAGA-AACCU
GGCUAGUCAGGGAGGGGUAAAAUUAA

5_5-5_internal_
UAUAUCAACCUACUAAUCAUC

loop-symmetric_

AAUGC-UAAAA

20_5-5_internal_

loop-symmetric_

UGGAU-CUAGU

35_5-5_internal_

loop-symmetric_

AUUUG-GUCAC

50_5-5_internal_

loop-symmetric_

GUGAU-CCAAA

65_5-5_internal_

loop-symmetric_

AUAUG-GUACA

1535
-5_6-6_internal_
GAUACUUUAUCAUAUCUCUGGUUGGC

loop-symmetric_
UCACACAAAAUACAGUAAUCUUCUAUC

UCAGAG-AAGCAC
CUACGCACAGGGAGGCCUACCUUUAAU

6_6-6_internal_
AUAUAAGCACACUAAUCAUC

loop-symmetric_

AUGCCC-CCUACC

22_6-6_internal_

loop-symmetric_

GAUCCU-CCUACG

38_6-6_internal_

loop-symmetric_

UGCAUC-UACAGU

54_6-6_internal_

loop-symmetric_

UGAGUG-GUUGGC

70_6-6_internal_

loop-symmetric_

UCACAA-CUUUAU

1536
-4_7-7_internal_
GAUAUUGUGACAUAUGCAUAAUCUCA

loop-symmetric_
UCACACUUCAUUCGCAAAUCUUCGCGA

UCAGAGA-
UGCUCCACAGGGAUUUCCCUUUUUAAU

CACCCCC
AUACACCCCCACUAAUCAUC

7_7-7_internal_

loop-symmetric_

UGCCCCC-

UUUCCCU

24_7-7_internal_

loop-symmetric_

UCCUAUA-

GCGAUGC

41_7-7_internal_

loop-symmetric_

AUCUUUU-

UUCAUUC

58_7-7_internal_

loop-symmetric_

UGCAGAG-

GCAUAAU

1537
-3_8-8_internal_
GAUAUUGUGAGCUGCAAAUGCACUCA

loop-symmetric_
UCUGUGACCCGAUGCAAAUCCUACACA

UCAGAGAU-
AGAUCCACAGGCAUUGCUGAUUUUAA

UUGGGCGU
UAUUUGGGCGUACUAAUCAUC

8_8-8_internal_

loop-symmetric_

GCCCCCUC-

CAUUGCUG

26_8-8_internal_

loop-symmetric_

CUAUAGAA-

CUACACAA

44_8-8_internal_

loop-symmetric_

UUUUGUGU-

UGUGACCC

62_8-8_internal_

loop-symmetric_

GAGAUAUG-

GCUGCAAA

1538
-7_2-2_bulge-
GACCUUGUGACAUAUCGAUGCACUCAU

symmetric_
CACCGAAAAGAUGCAAACAUUCUAUAG

AG-GA
GAUCAUCAGGGAGGGGGCUCUUUAAU

6_2-2_bulge-
AUAUCUGAGAACUAAUCAUC

symmetric_

AU-UC

20_2-2_bulge-

symmetric_

UG-AU

34_2-2_bulge-

symmetric_

GA-CA

48_2-2_bulge-

symmetric_

GU-CG

62_2-2_bulge-

symmetric_

GA-GA

76_2-2_bulge-

symmetric_

UA-CC

1539
-6_3-3_bulge-
GAUAUUGUGAACCAUCUCUGCACUCCG

symmetric_
GACACAAAAGAUGGUUAUCUUCUAUA

AGA-CAG
GGUAGCACAGGGAGGGGAACUUUUAA

7_3-3_bulge-
UAUAUCCAGGAACUAAUCAUC

symmetric_

UGC-AAC

22_3-3_bulge-

symmetric_

GAU-UAG

37_3-3_bulge-

symmetric_

UUG-GUU

52_3-3_bulge-

symmetric_

GAU-CGG

67_3-3_bulge-

symmetric_

AUG-ACC

1540
-5_4-4_bulge-
GAUAACAAGACAUAUCUCUGGUAGCA

symmetric_
UCACACAAAACUCCCAAAUCUUCUAUC

AGAG-AUAA

8_4-4_bulge-

symmetric_

GCCC-CUCG

24_4-4_bulge-
CCUUCCACAGGGAGGCUCGAUUUUAAU

symmetric_
AUAUAUAAGAACUAAUCAUC

UCCU-CCCU

40_4-4_bulge-

symmetric_

CAUC-CUCC

56_4-4_bulge-

symmetric_

AGUG-GUAG

72_4-4_bulge-

symmetric_

ACAA-ACAA

1541
-4_5-5_internal_
GAUAUUGUGACAUAUGAAUUCACUCA

loop-symmetric_
UCACACUUUAAAUGCAAAUCUUCACUC

AGAGA-CAGGC
UGAUCCACAGGGAUCACUCAUUUUAAU

9_5-5_internal_
AUACAGGCGAACUAAUCAUC

loop-symmetric_

CCCCC-UCACU

26_5-5_internal_

loop-symmetric_

CUAUA-ACUCU

43_5-5_internal_

loop-symmetric_

CUUUU-UUUAA

60_5-5_internal_

loop-symmetric_

CAGAG-GAAUU

1542
-3_6-6_internal_
GAUAUUGUGAGUUCCGUCUGCACUCAU

loop-symmetric_
CUGAAAUAAGAUGCAAAUCGCAGAGA

AGAGAU-CAGCCC
GGAUCCACAGGCCCACAGCAUUUUAAU

10_6-6_internal_
AUCAGCCCGAACUAAUCAUC

loop-symmetric_

CCCCUC-CCCACA

28_6-6_internal_

loop-symmetric_

AUAGAA-GCAGAG

46_6-6_internal_

loop-symmetric_

UUGUGU-UGAAAU

64_6-6_internal_

loop-symmetric_

GAUAUG-GUUCCG

1543
-2_7-7_internal_
GAUAUCCGAAGUUAUCUCUGCACUACC

loop-symmetric_
CCCUCAAAAGAUGCAACAAAUGGAUAG

AGAGAUA-
GAUCCACACCUCGACGGCAUUUUAAUA

AAGGCCG
AAGGCCGGAACUAAUCAUC

11_7-7_internal_

loop-symmetric_

CCCUCCC-

CCUCGAC

30_7-7_internal_

loop-symmetric_

AGAAGAU-

CAAAUGG

49_7-7_internal_

loop-symmetric_

UGUGAUG-

ACCCCCU

68_7-7_internal_

loop-symmetric_

UGUCACA-

CCGAAGU

1544
-1_8-8_internal_
GAUAUUGUGACAUAUCUCUGAAGGGU

loop-symmetric_
AGACACAAAAGAUGACCUGUACCUAUA

AGAGAUAU-
GGAUCCAGUAUACAAGGGCAUUUUAA

UGUGAUAA
UUGUGAUAAGAACUAAUCAUC

12_8-8_internal_

loop-symmetric_

CCUCCCUG-

GUAUACAA

32_8-8_internal_

loop-symmetric_

AAGAUUUG-

ACCUGUAC

52_8-8_internal_

loop-symmetric_

GAUGAGUG-

AAGGGUAG

1545
-5_2-2_bulge-
GAUAAGGUGACAUAUCUCUGGUCUCA

symmetric_
UCACACAAAACCUGCAAAUCUUCUAUU

AG-GC
UGAUCCACAGGGAGGAUGCAUUUUAA

10_2-2_bulge-
UAUAUGCCUGAACUAAUCAUC

symmetric_

CC-AU

26_2-2_bulge-

symmetric_

CU-UU

42_2-2_bulge-

symmetric_

UC-CC

58_2-2_bulge-

symmetric_

UG-GU

74_2-2_bulge-

symmetric_

AA-AG

1546
-4_3-3_bulge-
GAUAUUGUGACAUAUAUAUGCACUCA

symmetric_
UCACACCUUAGAUGCAAAUCUUCCCAA

AGA-GGA
GGAUCCACAGGGAUAAGGCAUUUUAA

11_3-3_bulge-
UAUAGGACUGAACUAAUCAUC

symmetric_

CCC-UAA

28_3-3_bulge-

symmetric_

AUA-CCA

45_3-3_bulge-

symmetric_

UUU-CUU

62_3-3_bulge-

symmetric_

GAG-AUA

1547
-3_4-4_bulge-
GAUAUUGUGAGCCUUCUCUGCACUCAU

symmetric_
CUGUGAAAAGAUGCAAAUCCGGCAUA

AGAU-UAGG
GGAUCCACAGGCACCGGGCAUUUUAAU

12_4-4_bulge-
AUUAGGCUGAACUAAUCAUC

symmetric_

CCUC-CACC

30_4-4_bulge-

symmetric_

AGAA-CGGC

48_4-4_bulge-

symmetric_

GUGU-UGUG

66_4-4_bulge-

symmetric_

UAUG-GCCU

1548
-2_5-5_internal_
GAUAUGCUUCCAUAUCUCUGCACUAUA

loop-symmetric_
GUCACAAAAGAUGCAAUAAUCCUAUA

AGAUA-AUGAC
GGAUCCACAUUACCGGGGCAUUUUAAU

13_5-5_internal_
AAUGACCUGAACUAAUCAUC

loop-symmetric_

CUCCC-UUACC

32_5-5_internal_

loop-symmetric_

AAGAU-UAAUC

51_5-5_internal_

loop-symmetric_

UGAUG-AUAGU

70_5-5_internal_

loop-symmetric_

UCACA-GCUUC

1549
-1_6-6_internal_
GAUAUUGUGACAUAUCUCUGAUGUGU

loop-symmetric_
UCACACAAAAGAUGAACUCGUUCUAUA

AGAUAU-UAAGAC
GGAUCCAAUUACUGGGGGCAUUUUAA

14_6-6_internal_
UUAAGACCUGAACUAAUCAUC

loop-symmetric_

UCCCUG-AUUACU

34_6-6_internal_

loop-symmetric_

GAUUUG-AACUCG

54_6-6_internal_

loop-symmetric_

UGAGUG-AUGUGU

1550
-6->0_7-7_
GAUAUUGUGACAUAUCGGUCGAAUCA

internal_
UCACACAAAAGCGAGUUUUCUUCUAUA

loop-symmetric_
GGAUCAUUAAAAAGGGGGCAUUUUAA

AGAUAUA-
GAUUUACCUGAACUAAUCAUC

GAUUUAC

15_7-7_internal_

loop-symmetric_

CCCUGUG-

AUUAAAA

36_7-7_internal_

loop-symmetric_

UUUGCAU-

CGAGUUU

57_7-7_internal_

loop-symmetric_

GUGCAGA-

GGUCGAA

1551
-6->1_8-8_
GAUAUUGUGACAACCACGACCACUCAU

internal_
CACACAAUAAAAACUAAUCUUCUAUAG

loop-symmetric_
GAAAGUAUCAGAGGGGGCAUUUUAUG

AGAUAUAU-
CGCUUGCUGAACUAAUCAUC

UGCGCUUG

16_8-8_internal_

loop-symmetric_

CCUGUGGA-

AAGUAUCA

38_8-8_internal_

loop-symmetric_

UGCAUCUU-

UAAAAACU

60_8-8_internal_

loop-symmetric_

CAGAGAUA-

ACCACGAC

1552
-3_2-2_bulge-
GAUAUUGUGAGCUAUCUCUGCACUCAU

symmetric_
CCGACAAAAGAUGCAAAUCGGCUAUAG

AU-CA
GAUCCACAGGUUGGGGGCAUUUUAAU

14_2-2_bulge-
AUCACUCUGAACUAAUCAUC

symmetric_

UC-UU

32_2-2_bulge-

symmetric_

AA-GG

50_2-2_bulge-

symmetric_

GU-CG

68_2-2_bulge-

symmetric_

UG-GC

1553
-2_3-3_bulge-
GAUAUCCGGACAUAUCUCUGCACUGUG

symmetric_
CACACAAAAGAUGCAAUGGUUCUAUA

AUA-GCC
GGAUCCACAACCAGGGGGCAUUUUAAU

15_3-3_bulge-
AGCCCUCUGAACUAAUCAUC

symmetric_

CCC-ACC

34_3-3_bulge-

symmetric_

GAU-UGG

53_3-3_bulge-

symmetric_

AUG-GUG

72_3-3_bulge-

symmetric_

ACA-CCG

1554
-1_4-4_bulge-
GAUAUUGUGACAUAUCUCUGGUAACA

symmetric_
UCACACAAAAGAUGAUUCUCUUCUAUA

AUAU-CCAA
GGAUCCAAAUCGAGGGGGCAUUUUAA

16_4-4_bulge-
UCCAACUCUGAACUAAUCAUC

symmetric_

CCUG-AAUC

36_4-4_bulge-

symmetric_

UUUG-AUUC

56_4-4_bulge-

symmetric_

AGUG-GUAA

1555
-4->0_5-5_
GAUAUUGUGACAUAUCGACCAACUCAU

internal_
CACACAAAAGUCCGUAAUCUUCUAUAG

loop-symmetric_
GAUCGUCCUGGAGGGGGCAUUUUAAC

AUAUA-CUGAA
UGAACUCUGAACUAAUCAUC

17_5-5_internal_

loop-symmetric_

CUGUG-GUCCU

38_5-5_internal_

loop-symmetric_

UGCAU-UCCGU

59_5-5_internal_

loop-symmetric_

GCAGA-GACCA

1556
-4->1_6-6_
GAUAUUGUGACAGUGAAGUGCACUCA

internal_
UCACACAAUUAAAUCAAAUCUUCUAUA

loop-symmetric_
GGAAAGAAUGGGAGGGGGCAUUUUAU

AUAUAU-
AAGACCUCUGAACUAAUCAUC

UAAGAC

18_6-6_internal_

loop-symmetric_

UGUGGA-AAGAAU

40_6-6_internal_

loop-symmetric_

CAUCUU-UUAAAU

62_6-6_internal_

loop-symmetric_

GAGAUA-GUGAAG

1557
-4->2_7-7_
GAUAUUGUUUUUCACCUCUGCACUCAU

internal_
CACAGUUCAACUGCAAAUCUUCUAUAG

loop-symmetric_
CAGAAAAAGGGAGGGGGCAUUUUCUA

AUAUAUU-
UUUACUCUGAACUAAUCAUC

CUAUUUA

19_7-7_internal_

loop-symmetric_

GUGGAUC-

CAGAAAA

42_7-7_internal_

loop-symmetric_

UCUUUUG-

GUUCAAC

65_7-7_internal_

loop-symmetric_

AUAUGUC-

UUUUCAC

1558
-4->3_8-8_
GAUACGAGAAGUUAUCUCUGCACUCAU

internal_
CCUUGAUCCGAUGCAAAUCUUCUAUCC

loop-symmetric_
GUUAGUCAGGGAGGGGGCAUUUGCCU

AUAUAUUA-
AAAACUCUGAACUAAUCAUC

GCCUAAAA

20_8-8_internal_

loop-symmetric_

UGGAUCCU-

CCGUUAGU

44_8-8_internal_

loop-symmetric_

UUUUGUGU-

CUUGAUCC

68_8-8_internal_

loop-symmetric_

UGUCACAA-

CGAGAAGU

1559
0->1_2-2_bulge-
GAUAUUGUGACAGCUCUCUGCACUCAU

symmetric_
CACACAAUCGAUGCAAAUCUUCUAUAG

AU-UG
GAUACACAGGGAGGGGGCAUUUUAUG

22_2-2_bulge-
AUAUCUCUGAACUAAUCAUC

symmetric_

GA-UA

44_2-2_bulge-

symmetric_

UU-UC

66_2-2_bulge-

symmetric_

UA-GC

1560
0->2_3-3_bulge-
GAUAUUGUCCGAUAUCUCUGCACUCAU

symmetric_
CACAAACAAGAUGCAAAUCUUCUAUAG

AUU-UCG
UUCCCACAGGGAGGGGGCAUUUUUCGA

23_3-3_bulge-
UAUCUCUGAACUAAUCAUC

symmetric_

AUC-UUC

46_3-3_bulge-

symmetric_

UUG-AAC

69_3-3_bulge-

symmetric_

GUC-CCG

1561
0->3_4-4_bulge-
GAUAGGCCGACAUAUCUCUGCACUCAU

symmetric_
CUGUGAAAAGAUGCAAAUCUUCUAUC

AUUA-GUAG
UACUCCACAGGGAGGGGGCAUUUGUA

24_4-4_bulge-
GAUAUCUCUGAACUAAUCAUC

symmetric_

UCCU-CUAC

48_4-4_bulge-

symmetric_

GUGU-UGUG

72_4-4_bulge-

symmetric_

ACAA-GGCC

1562
0->4_5-5_internal_
GAUAUUGUGACAUAUCUCUGCACUCCC

loop-symmetric_
GUGACAAAAGAUGCAAAUCUUCUUUC

AUUAA-CGUUC
AUAUCCACAGGGAGGGGGCAUUCGUUC

25_5-5_internal_
AUAUCUCUGAACUAAUCAUC

loop-symmetric_

CCUAU-UUCAU

50_5-5_internal_

loop-symmetric_

GUGAU-CCGUG

1563
0->5_6-6_internal_
GAUAUUGUGACAUAUCUCUGCAGCGCU

loop-symmetric_
AACACAAAAGAUGCAAAUCUUGGAGCC

AUUAAA-
GAUCCACAGGGAGGGGGCAUCGUCACA

CGUCAC
UAUCUCUGAACUAAUCAUC

26_6-6_internal_

loop-symmetric_

CUAUAG-GGAGCC

52_6-6_internal_

loop-symmetric_

GAUGAG-GCGCUA

1564
0->6_7-7_internal_
GAUAUUGUGACAUAUCUCUAAAGAAU

loop-symmetric_
UCACACAAAAGAUGCAAAUCAUAUUU

AUUAAAA-
UGGAUCCACAGGGAGGGGGCAGAUUC

GAUUCUA
UAAUAUCUCUGAACUAAUCAUC

27_7-7_internal_

loop-symmetric_

UAUAGAA-

AUAUUUU

54_7-7_internal_

loop-symmetric_

UGAGUGC-

AAAGAAU

1565
0->7_8-8_internal_
GAUAUUGUGACAUAUCGAGAGUGACA

loop-symmetric_
UCACACAAAAGAUGCAAACGGUAUUA

AUUAAAAU-
AGGAUCCACAGGGAGGGGGCCUAUAAC

CUAUAACC
CAUAUCUCUGAACUAAUCAUC

28_8-8_internal_

loop-symmetric_

AUAGAAGA-

CGGUAUUA

56_8-8_internal_

loop-symmetric_

AGUGCAGA-

GAGAGUGA

1566
-6_6-6_internal_
GCCAUUGUGUGAUAUCUGAGCACUCCG

loop-symmetric_
CACACACCAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

45_2-2_bulge-

symmetric_

UU-CC

53_2-2_bulge-

symmetric_

AU-CG

61_2-2_bulge-

symmetric_

AG-GA

69_2-2_bulge-

symmetric_

GU-UG

77_2-2_bulge-

symmetric_

AU-CC

1567
-6_6-6_internal_
GAUAUGCAGACAUAGACCUGCACCUUU

loop-symmetric_
CACACUAUAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

45_3-3_bulge-

symmetric_

UUU-UAU

54_3-3_bulge-

symmetric_

UGA-CUU

63_3-3_bulge-

symmetric_

AGA-GAC

72_3-3_bulge-

symmetric_

ACA-GCA

1568
-6_6-6_internal_
GUUCGUGUGACCAAACUCUGCCAAGAU

loop-symmetric_
CACAGUAUAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

45_4-4_bulge-

symmetric_

UUUG-GUAU

55_4-4_bulge-

symmetric_

GAGU-CAAG

65_4-4_bulge-

symmetric_

AUAU-CAAA

75_4-4_bulge-

symmetric_

AUAU-UUCG

1569
-6_6-6_internal_
GAUAUUGUCCAAAAUCUCUCUUUCCAU

loop-symmetric_
CACUGUUCAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

45_5-5_internal_

loop-symmetric_

UUUGU-UGUUC

56_5-5_internal_

loop-symmetric_

AGUGC-CUUUC

67_5-5_internal_

loop-symmetric_

AUGUC-CCAAA

1570
-6_6-6_internal_
GUGAUUGUGACUAAUCUCUGCCGUCAU

loop-symmetric_
CACAAUAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

47_2-2_bulge-

symmetric_

UG-AU

57_2-2_bulge-

symmetric_

GU-CG

67_2-2_bulge-

symmetric_

AU-UA

77_2-2_bulge-

symmetric_

AU-UG

1571
-6_6-6_internal_
GAUAUUGUCCAAUAUCUCUAAUCUCAU

loop-symmetric_
CACUGUAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

47_3-3_bulge-

symmetric_

UGU-UGU

58_3-3_bulge-

symmetric_

UGC-AAU

69_3-3_bulge-

symmetric_

GUC-CCA

1572
-6_6-6_internal_
GAUAUCUUUACAUAUCUGGUGACUCA

loop-symmetric_
UCAACCUAAAGAUGCCUGACCUCUAUA

UUCAGA-GGAACU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

47_4-4_bulge-

symmetric_

UGUG-ACCU

59_4-4_bulge-

symmetric_

GCAG-GGUG

71_4-4_bulge-

symmetric_

CACA-CUUU

1573
-6_6-6_internal_
GAAAGUCUGACAUAUGCACCCACUCAU

loop-symmetric_
CUGAAUAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

47_5-5_internal_

loop-symmetric_

UGUGU-UGAAU

60_5-5_internal_

loop-symmetric_

CAGAG-GCACC

73_5-5_internal_

loop-symmetric_

CAAUA-AAGUC

1574
-6_6-6_internal_
GAUAUACUGACAUAUCUAAGCACUCAU

loop-symmetric_
CAGCCAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

49_2-2_bulge-

symmetric_

UG-GC

61_2-2_bulge-

symmetric_

AG-AA

73_2-2_bulge-

symmetric_

CA-AC

1575
-6_6-6_internal_
GAGUGUGUGACAUAUGAGUGCACUCA

loop-symmetric_
UCCUUCAAAAGAUGCCUGACCUCUAUA

UUCAGA-GGAACU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

49_3-3_bulge-

symmetric_

UGU-CUU

62_3-3_bulge-

symmetric_

GAG-GAG

75_3-3_bulge-

symmetric_

AUA-GUG

1576
-6_6-6_internal_
GAUAUUGUGACAUUGGCCUGCACUCAU

loop-symmetric_
GUAUCAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

49_4-4_bulge-

symmetric_

UGUG-GUAU

63_4-4_bulge-

symmetric_

AGAU-UGGC

1577
-6_6-6_internal_
GAUAUUGUGACCUUAAUCUGCACUCAG

loop-symmetric_
CCUUCAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

49_5-5_internal_

loop-symmetric_

UGUGA-GCCUU

64_5-5_internal_

loop-symmetric_

GAUAU-CUUAA

1578
-6_6-6_internal_
GAUAUUGUGACAUUGCUCUGCACUCAU

loop-symmetric_
GCCACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU

3_1-1_mismatch_

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

51_2-2_bulge-
GAUCCACAGGGAGGGGGCAUUUCAAU

symmetric_
AUAUCGGAACUCUAAUCAUC

UG-GC

65_2-2_bulge-

symmetric_

AU-UG

1579
-6_6-6_internal_
GAUAUUGUGACUACUCUCUGCACUCAA

loop-symmetric_
GCCACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

51_3-3_bulge-

symmetric_

UGA-AGC

66_3-3_bulge-

symmetric_

UAU-UAC

1580
-6_6-6_internal_
GAUAUUGUGUGUCAUCUCUGCACUCCU

loop-symmetric_
ACCACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

51_4-4_bulge-

symmetric_

UGAU-CUAC

67_4-4_bulge-

symmetric_

AUGU-UGUC

1581
-6_6-6_internal_
GAUAUUGGCAGUUAUCUCUGCACUGU

loop-symmetric_
AGUCACAAAAGAUGCCUGACCUCUAUA

UUCAGA-GGAACU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

51_5-5_internal_

loop-symmetric_

UGAUG-GUAGU

68_5-5_internal_

loop-symmetric_

UGUCA-GCAGU

1582
-6_6-6_internal_
GAUAUUGUGUAAUAUCUCUGCACUCU

loop-symmetric_
ACACACAAAAGAUGCCUGACCUCUAUA

UUCAGA-GGAACU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

53_2-2_bulge-

symmetric_

AU-UA

69_2-2_bulge-

symmetric_

GU-UA

1583
-6_6-6_internal_
GAUAUUGAUUCAUAUCUCUGCACUGCG

loop-symmetric_
CACACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

53_3-3_bulge-

symmetric_

AUG-GCG

70_3-3_bulge-

symmetric_

UCA-AUU

1584
-6_6-6_internal_
GAUAUAUAAACAUAUCUCUGCACAGCC

loop-symmetric_
CACACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

53_4-4_bulge-

symmetric_

AUGA-AGCC

71_4-4_bulge-

symmetric_

CACA-AUAA

1585
-6_6-6_internal_
GAUUCAAGGACAUAUCUCUGCAGAAA

loop-symmetric_
ACACACAAAAGAUGCCUGACCUCUAUA

UUCAGA-GGAACU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

53_5-5_internal_

loop-symmetric_

AUGAG-GAAAA

72_5-5_internal_

loop-symmetric_

ACAAU-UCAAG

1586
-6_6-6_internal_
GAUAUCCUGACAUAUCUCUGCACAAAU

loop-symmetric_
CACACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

55_2-2_bulge-

symmetric_

GA-AA

73_2-2_bulge-

symmetric_

CA-CC

1587
-6_6-6_internal_
GAUUCAGUGACAUAUCUCUGCAGCGAU

loop-symmetric_
CACACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

55_3-3_bulge-

symmetric_

GAG-GCG

74_3-3_bulge-

symmetric_

AAU-UCA

1588
-6_6-6_internal_
GCGCGUGUGACAUAUCUCUGCCAAAAU

loop-symmetric_
CACACAAAAGAUGCCUGACCUCUAUAG

UUCAGA-GGAACU
GAUCCACAGGGAGGGGGCAUUUCAAU

3_1-1_mismatch_
AUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

55_4-4_bulge-

symmetric_

GAGU-CAAA

75_4-4_bulge-

symmetric_

AUAU-CGCG

1589
-6_6-6_internal_
GAUAUUGUGACAUAUCUCUGAUGGGA

loop-symmetric_
UCACACAAAAGAUGCCUGACCUCUAUA

UUCAGA-GGAACU
GGAUCCACAGGGAGGGGGCAUUUCAA

3_1-1_mismatch_
UAUAUCGGAACUCUAAUCAUC

A-C

33_6-6_internal_

loop-symmetric_

AGAUUU-CUGACC

55_5-5_internal_

loop-symmetric_

GAGUG-AUGGG

TABLE 2

Percent Editing of As in ATTAAA of DUX4 mRNA by ADAR1, ADAR2, or ADAR1 and ADAR2

SEQ

ID
A1/
A1/
A1/
A1/
A1/
A2/
A2/
A2/
A2/
A2/
A1 +
A1 +
A1 +
A1 +
A1 +

NO
P0
P3
P4
P5
Any
P0
P3
P4
P5
Any
2/P0
2/P3
2/P4
2/P5
2/Any

2
30.6%
58.0%
30.4%
22.9%
70.7%
28.5%
59.9%
40.6%
41.6%
87.0%
29.0%
60.7%
39.1%
33.8%
87.3%

3
20.4%
64.7%
35.9%
30.8%
74.4%
11.4%
69.8%
52.2%
46.3%
89.1%
15.0%
70.7%
45.0%
38.1%
89.6%

4
14.5%
57.7%
37.7%
21.6%
72.1%
9.4%
61.7%
48.9%
46.8%
89.3%
12.6%
62.4%
45.9%
37.0%
89.2%

5
14.3%
60.1%
32.5%
31.8%
73.8%
7.3%
59.6%
49.6%
46.7%
89.4%
12.2%
63.6%
46.8%
42.9%
89.9%

6
15.3%
61.4%
30.7%
23.0%
75.5%
9.9%
63.3%
44.8%
37.7%
87.8%
12.5%
64.3%
41.2%
34.2%
88.9%

7
43.1%
68.0%
25.5%
10.6%
78.4%
30.3%
49.1%
43.5%
45.1%
88.3%
35.1%
53.9%
42.7%
39.8%
90.2%

8
17.6%
81.0%
23.3%
8.9%
86.4%
11.8%
80.6%
69.4%
55.6%
93.5%
13.6%
82.5%
59.4%
43.9%
94.1%

9
17.4%
65.7%
38.0%
9.8%
79.9%
7.8%
56.9%
49.7%
50.1%
90.1%
13.4%
61.3%
50.3%
44.3%
91.2%

10
10.6%
76.9%
23.6%
11.0%
84.1%
8.5%
49.4%
56.0%
52.5%
90.8%
9.6%
52.3%
47.3%
47.7%
91.5%

11
16.7%
67.5%
24.1%
10.2%
79.9%
7.1%
63.2%
53.4%
51.8%
91.7%
10.6%
62.7%
50.1%
47.0%
91.6%

12
37.0%
65.2%
26.7%
12.6%
77.7%
31.9%
52.9%
45.1%
39.2%
88.9%
35.9%
56.2%
41.4%
35.6%
89.3%

13
18.3%
71.6%
30.1%
16.8%
78.7%
13.5%
68.3%
54.7%
37.3%
88.0%
14.4%
74.0%
49.6%
27.8%
90.4%

14
10.1%
77.5%
19.5%
14.4%
84.8%
8.2%
52.9%
57.9%
55.0%
92.0%
9.0%
53.9%
45.6%
45.9%
91.9%

15
22.9%
77.3%
22.9%
8.9%
88.0%
7.8%
70.7%
62.6%
54.1%
93.3%
10.3%
70.8%
59.2%
49.4%
94.8%

16
35.8%
69.8%
39.8%
23.2%
81.7%
36.5%
61.7%
40.9%
35.9%
88.8%
34.3%
58.6%
36.4%
30.2%
91.3%

17
22.6%
82.5%
43.1%
41.2%
87.9%
19.1%
82.0%
67.9%
44.9%
93.5%
13.7%
81.8%
50.3%
28.2%
93.1%

18
16.1%
66.1%
45.7%
20.1%
77.5%
10.0%
56.7%
48.9%
42.6%
85.8%
11.8%
58.0%
44.1%
31.9%
87.8%

19
12.1%
72.3%
40.5%
44.0%
82.3%
10.1%
55.2%
50.0%
47.9%
89.9%
10.0%
54.8%
42.6%
41.9%
90.8%

20
16.1%
67.8%
31.8%
22.2%
79.4%
8.7%
63.0%
48.0%
40.1%
89.7%
13.1%
63.6%
43.0%
34.6%
89.4%

21
42.3%
69.2%
28.6%
26.0%
86.3%
50.6%
61.5%
47.7%
42.3%
91.4%
46.8%
58.3%
39.7%
30.4%
92.6%

22
16.9%
70.9%
41.7%
42.1%
79.4%
24.7%
74.0%
51.3%
36.5%
90.1%
18.2%
72.8%
42.8%
27.6%
90.5%

23
16.2%
54.2%
33.8%
16.0%
83.2%
15.3%
59.9%
49.6%
41.6%
90.3%
15.2%
52.7%
40.7%
24.5%
90.9%

24
11.2%
66.1%
40.6%
48.7%
82.8%
10.7%
57.2%
47.1%
46.5%
90.4%
10.4%
54.9%
38.9%
39.8%
91.2%

25
11.6%
65.4%
51.7%
37.3%
78.6%
11.7%
61.1%
41.8%
37.3%
87.9%
11.9%
54.7%
36.4%
28.4%
86.3%

26
36.0%
53.0%
22.1%
17.6%
74.5%
38.4%
60.7%
35.9%
33.3%
85.5%
36.3%
59.7%
34.7%
27.4%
87.8%

27
21.8%
71.2%
24.1%
26.3%
80.7%
32.1%
70.2%
48.5%
33.3%
87.1%
23.0%
75.5%
44.7%
26.7%
90.6%

28
14.2%
46.9%
26.4%
15.3%
77.5%
22.6%
64.5%
50.2%
39.7%
90.7%
14.5%
54.2%
36.1%
23.4%
89.5%

29
12.3%
58.6%
24.3%
36.6%
81.7%
17.3%
61.4%
42.9%
43.2%
89.6%
12.3%
60.7%
38.0%
37.8%
91.7%

30
11.9%
66.3%
30.0%
33.5%
86.9%
24.8%
68.9%
44.9%
40.1%
92.1%
13.9%
69.0%
44.2%
33.6%
93.0%

31
36.4%
57.9%
24.1%
18.4%
73.3%
37.2%
60.9%
35.3%
29.1%
86.6%
40.8%
62.3%
34.3%
25.8%
88.7%

32
25.6%
67.8%
21.7%
24.8%
80.1%
31.6%
73.8%
52.4%
37.2%
89.7%
20.7%
77.1%
47.9%
26.5%
91.7%

33
15.2%
42.3%
24.8%
11.9%
80.9%
25.2%
62.3%
48.0%
41.2%
90.4%
15.1%
54.6%
39.1%
23.5%
89.9%

34
14.5%
56.0%
22.6%
28.2%
75.5%
12.3%
62.2%
42.1%
39.1%
88.7%
12.5%
60.6%
35.8%
34.7%
89.6%

35
18.3%
52.0%
22.4%
18.3%
74.0%
16.1%
63.8%
38.2%
31.7%
87.5%
16.1%
61.5%
35.6%
25.8%
87.2%

36
37.5%
58.7%
22.7%
15.7%
74.1%
37.8%
63.8%
43.0%
30.3%
86.7%
35.9%
60.7%
36.7%
24.6%
86.7%

37
24.3%
57.4%
22.0%
16.7%
71.0%
23.5%
66.6%
50.3%
37.7%
87.9%
20.1%
66.8%
39.3%
21.9%
86.7%

38
20.3%
47.8%
28.6%
11.7%
78.9%
25.1%
62.5%
49.0%
31.1%
88.5%
21.4%
60.6%
43.7%
23.9%
90.5%

39
17.2%
49.9%
18.9%
17.6%
72.2%
11.2%
63.2%
44.5%
39.7%
88.0%
14.4%
56.8%
31.3%
27.6%
87.9%

40
18.1%
51.7%
21.2%
15.7%
72.2%
13.9%
63.7%
41.3%
34.0%
84.5%
14.3%
61.2%
36.6%
26.3%
87.3%

41
29.0%
54.4%
24.0%
18.0%
67.9%
25.0%
53.3%
34.4%
27.7%
84.1%
26.7%
56.3%
34.2%
24.1%
85.1%

42
25.0%
59.4%
30.0%
21.4%
71.5%
13.9%
62.3%
47.1%
40.9%
86.6%
19.0%
68.2%
44.1%
27.4%
87.9%

43
14.1%
64.9%
39.4%
19.4%
80.5%
15.6%
62.0%
44.2%
36.2%
87.0%
17.9%
68.7%
48.6%
30.2%
90.4%

44
17.1%
56.6%
22.3%
18.5%
72.6%
10.3%
60.3%
33.9%
32.4%
84.8%
14.5%
60.0%
32.8%
27.9%
86.4%

45
16.5%
61.0%
29.3%
20.4%
73.1%
7.2%
57.2%
39.2%
41.2%
85.0%
11.1%
64.9%
38.2%
36.8%
87.8%

46
32.1%
55.7%
25.1%
14.3%
67.9%
23.8%
56.2%
36.8%
30.1%
82.8%
29.4%
58.7%
33.2%
21.5%
84.9%

47
22.3%
59.9%
30.2%
20.5%
71.1%
12.6%
61.3%
45.6%
37.3%
85.0%
17.6%
67.0%
43.5%
28.0%
86.4%

48
15.7%
56.9%
35.0%
20.8%
72.0%
8.2%
55.4%
40.3%
38.2%
86.1%
13.6%
62.0%
43.2%
34.9%
87.5%

49
15.4%
55.2%
25.0%
19.3%
70.0%
8.4%
59.5%
36.8%
31.5%
85.9%
13.7%
60.6%
34.3%
26.5%
86.0%

50
21.8%
63.3%
25.5%
16.9%
78.6%
10.4%
67.0%
49.0%
33.1%
89.7%
15.1%
67.4%
41.1%
27.0%
90.6%

51
29.5%
57.3%
29.6%
15.7%
67.7%
20.0%
56.4%
39.6%
33.6%
82.8%
28.7%
57.4%
36.5%
25.9%
83.9%

52
27.8%
67.5%
41.0%
25.2%
76.4%
9.7%
64.6%
48.9%
45.5%
84.3%
17.6%
69.6%
50.2%
36.2%
87.7%

53
18.5%
55.6%
35.9%
15.7%
71.3%
9.9%
58.9%
45.7%
41.0%
85.7%
15.7%
61.0%
42.0%
27.1%
86.1%

54
14.1%
59.8%
28.7%
21.3%
74.1%
8.3%
56.5%
37.8%
33.1%
85.5%
13.7%
63.5%
36.3%
28.8%
88.0%

55
17.1%
60.3%
33.0%
16.1%
72.3%
7.9%
61.0%
43.1%
36.9%
86.0%
13.4%
63.3%
38.3%
27.6%
86.9%

56
34.2%
62.1%
37.9%
18.0%
73.5%
17.2%
58.9%
39.3%
39.3%
86.0%
28.6%
62.1%
41.7%
31.4%
87.2%

57
21.5%
63.5%
42.7%
28.5%
74.0%
8.8%
62.4%
45.6%
43.3%
86.6%
16.9%
68.1%
46.6%
33.9%
88.5%

58
16.9%
57.2%
37.1%
15.6%
72.9%
9.2%
59.5%
43.6%
41.8%
88.0%
14.4%
60.4%
42.0%
30.4%
87.9%

59
14.0%
56.8%
30.6%
22.9%
70.2%
8.4%
56.9%
42.7%
36.8%
86.2%
14.0%
60.8%
40.8%
33.0%
87.6%

60
16.7%
59.9%
33.7%
18.0%
73.4%
7.6%
57.2%
40.5%
37.1%
84.7%
14.2%
60.9%
37.3%
28.3%
87.2%

61
29.5%
61.2%
39.5%
25.0%
71.9%
19.0%
54.5%
36.7%
40.5%
85.5%
25.8%
62.6%
43.1%
37.9%
88.0%

62
20.2%
59.9%
40.6%
31.8%
70.1%
8.9%
61.3%
41.8%
39.4%
84.6%
15.8%
65.0%
44.8%
34.1%
86.6%

63
17.0%
65.3%
48.2%
22.9%
76.0%
7.7%
52.8%
40.4%
44.5%
85.3%
14.8%
64.8%
45.1%
34.4%
87.1%

64
12.8%
62.8%
37.7%
29.9%
74.0%
6.9%
52.1%
46.7%
44.6%
87.4%
13.0%
63.9%
43.8%
37.1%
88.8%

65
14.5%
61.1%
40.7%
20.7%
73.2%
6.9%
56.6%
38.2%
38.5%
87.2%
14.1%
62.6%
41.5%
33.0%
87.2%

66
27.7%
59.8%
39.2%
25.0%
71.2%
16.9%
46.7%
32.9%
35.7%
85.2%
25.1%
61.1%
39.6%
34.7%
86.3%

67
20.6%
65.5%
49.1%
41.1%
75.2%
8.0%
61.0%
41.4%
40.7%
85.2%
14.2%
69.6%
47.5%
38.9%
87.2%

68
17.3%
63.8%
48.1%
34.6%
75.5%
8.7%
53.5%
38.9%
43.9%
87.4%
15.7%
63.2%
44.7%
38.8%
87.8%

69
15.1%
66.3%
47.7%
42.2%
77.1%
6.4%
49.0%
39.5%
40.2%
86.6%
14.0%
62.9%
45.4%
40.9%
87.5%

70
14.5%
60.2%
35.3%
28.6%
72.7%
7.6%
54.8%
35.2%
38.3%
86.7%
12.8%
63.2%
39.2%
34.2%
88.5%

71
31.5%
63.2%
44.8%
35.2%
73.5%
19.2%
47.0%
33.0%
38.7%
83.6%
26.5%
62.6%
41.9%
38.6%
86.6%

72
24.9%
75.4%
63.1%
60.0%
82.2%
8.2%
66.6%
40.9%
44.1%
87.5%
15.7%
73.4%
53.8%
52.3%
89.9%

73
17.6%
61.4%
45.3%
35.5%
73.6%
7.9%
48.6%
35.3%
39.2%
87.1%
16.5%
63.4%
42.4%
33.8%
88.3%

74
15.1%
62.2%
44.5%
40.1%
72.8%
6.5%
47.5%
41.1%
41.1%
86.4%
13.0%
61.9%
41.2%
37.2%
86.7%

75
14.6%
67.6%
49.8%
36.5%
77.9%
6.0%
51.5%
33.7%
42.2%
85.7%
13.2%
67.3%
45.1%
39.4%
90.0%

76
19.5%
62.4%
44.9%
41.2%
72.2%
9.8%
58.5%
35.3%
32.5%
83.2%
14.5%
66.8%
42.0%
38.9%
86.2%

77
16.7%
67.3%
52.3%
42.0%
77.0%
6.5%
43.4%
33.5%
34.5%
87.3%
12.8%
62.6%
43.0%
38.5%
87.2%

78
14.6%
60.8%
42.5%
38.4%
71.7%
6.2%
44.8%
35.3%
34.7%
83.4%
12.0%
60.1%
40.6%
38.1%
85.7%

79
15.8%
61.5%
37.4%
30.0%
72.7%
8.4%
53.3%
36.0%
38.8%
87.1%
14.6%
62.5%
38.0%
36.1%
87.0%

80
25.6%
59.0%
37.7%
29.9%
70.6%
17.2%
48.9%
33.5%
36.3%
85.8%
24.4%
61.8%
38.7%
33.1%
86.7%

81
16.6%
65.5%
45.5%
43.6%
75.4%
8.8%
63.9%
40.8%
36.9%
88.0%
14.6%
67.4%
44.9%
40.7%
87.6%

82
14.6%
63.0%
43.2%
28.8%
74.5%
8.3%
48.7%
37.2%
43.0%
87.5%
13.4%
64.7%
44.2%
41.1%
88.9%

83
13.6%
60.7%
37.9%
34.9%
72.8%
7.0%
44.6%
37.6%
35.6%
86.6%
13.9%
59.9%
39.3%
36.2%
87.6%

84
14.6%
67.1%
39.6%
34.0%
77.3%
6.7%
53.9%
36.4%
39.4%
88.4%
13.7%
63.7%
38.4%
37.0%
88.1%

85
25.6%
58.9%
36.4%
25.2%
70.7%
20.2%
47.3%
33.7%
37.1%
83.9%
27.0%
60.6%
39.8%
31.6%
86.4%

86
16.7%
66.1%
45.0%
44.1%
74.6%
8.4%
65.1%
41.9%
39.3%
86.9%
15.3%
70.6%
43.7%
38.4%
88.3%

87
14.5%
61.8%
43.7%
28.7%
74.0%
7.2%
46.6%
37.3%
37.2%
86.0%
13.7%
63.4%
44.1%
36.4%
87.1%

88
12.2%
65.5%
37.4%
37.9%
76.3%
6.9%
55.2%
51.9%
50.1%
90.3%
10.7%
65.4%
49.7%
46.7%
89.5%

89
13.4%
62.7%
34.2%
27.1%
73.6%
7.1%
55.0%
36.3%
38.4%
87.9%
15.1%
64.9%
41.1%
35.6%
89.9%

90
26.5%
69.3%
42.5%
31.1%
78.8%
26.3%
51.1%
38.4%
41.4%
89.2%
34.7%
65.8%
41.0%
36.6%
88.8%

91
16.1%
62.8%
42.0%
38.6%
73.9%
8.9%
64.7%
40.8%
35.1%
88.4%
18.3%
68.5%
41.2%
35.5%
89.2%

92
12.8%
57.0%
37.8%
24.3%
70.1%
6.6%
48.1%
36.7%
36.0%
85.5%
13.9%
61.5%
41.3%
33.4%
88.0%

93
13.6%
60.6%
35.0%
31.5%
72.2%
6.2%
49.2%
44.2%
44.1%
86.5%
12.7%
61.8%
42.1%
38.7%
88.5%

94
15.6%
61.3%
33.7%
25.9%
72.7%
6.8%
50.9%
32.5%
34.5%
84.2%
13.1%
62.0%
36.8%
33.2%
86.7%

95
25.4%
57.6%
34.1%
23.9%
68.4%
22.5%
46.4%
34.1%
36.5%
82.8%
26.5%
57.6%
36.7%
31.1%
84.7%

96
16.9%
63.5%
40.6%
35.5%
73.1%
9.3%
68.9%
48.7%
42.9%
89.6%
17.5%
72.8%
46.8%
38.9%
90.3%

97
13.3%
56.3%
36.4%
22.3%
70.6%
6.3%
48.7%
37.5%
35.0%
86.7%
13.3%
60.9%
41.2%
30.4%
87.2%

98
14.0%
60.2%
32.2%
24.7%
72.9%
7.0%
56.0%
40.4%
37.0%
87.4%
12.5%
62.9%
38.4%
31.8%
87.5%

99
27.1%
57.6%
32.0%
21.5%
70.7%
23.6%
50.6%
37.4%
36.9%
86.2%
29.5%
58.6%
40.3%
33.7%
87.2%

100
19.2%
62.2%
38.6%
33.6%
70.9%
10.0%
70.6%
49.3%
42.7%
89.1%
16.4%
72.6%
47.3%
36.2%
89.1%

101
15.3%
58.5%
38.7%
21.1%
71.5%
8.0%
53.3%
43.3%
41.1%
88.0%
13.3%
61.1%
44.3%
34.6%
89.2%

102
14.2%
56.2%
31.2%
27.2%
68.5%
7.7%
48.5%
42.9%
42.7%
86.7%
12.8%
56.9%
42.9%
40.4%
87.5%

103
15.1%
58.8%
32.1%
24.1%
72.6%
7.7%
56.5%
37.1%
39.2%
86.5%
11.9%
60.5%
37.9%
34.0%
90.0%

104
29.1%
57.9%
32.0%
21.0%
70.8%
30.4%
55.9%
40.9%
41.7%
87.1%
32.2%
58.6%
38.2%
36.1%
87.9%

105
20.0%
62.1%
38.7%
31.6%
73.2%
9.1%
67.7%
47.4%
41.8%
87.7%
15.4%
71.1%
45.4%
37.4%
89.1%

106
15.8%
58.1%
37.9%
22.5%
71.3%
7.8%
51.8%
40.9%
42.3%
88.7%
12.4%
60.8%
45.2%
38.1%
88.7%

107
14.7%
61.3%
33.1%
30.1%
73.2%
6.8%
55.1%
47.3%
46.3%
88.3%
12.3%
63.0%
44.6%
42.9%
89.6%

108
17.0%
59.8%
31.2%
21.7%
72.1%
7.1%
60.1%
45.4%
47.2%
90.1%
13.4%
63.1%
42.0%
41.2%
91.6%

109
32.0%
58.6%
33.5%
20.8%
69.1%
30.2%
56.8%
42.2%
42.6%
87.6%
34.2%
59.8%
40.0%
37.5%
87.4%

110
24.0%
61.9%
39.4%
32.8%
71.9%
11.3%
69.6%
53.2%
46.2%
89.1%
16.9%
73.3%
50.2%
40.7%
89.9%

111
16.8%
56.3%
37.2%
20.0%
70.0%
8.4%
58.0%
46.2%
45.7%
88.7%
13.5%
58.2%
44.6%
40.2%
89.0%

112
14.6%
57.8%
31.0%
27.4%
71.0%
5.6%
53.6%
49.5%
47.0%
88.4%
12.2%
63.8%
49.7%
47.1%
91.1%

113
17.3%
65.9%
34.2%
21.9%
77.0%
7.6%
64.5%
46.9%
45.7%
89.4%
12.3%
67.3%
42.3%
40.0%
92.0%

114
36.1%
61.4%
34.6%
22.4%
72.1%
36.3%
62.3%
49.1%
47.6%
89.7%
39.0%
64.1%
45.4%
41.0%
90.4%

115
31.1%
70.0%
47.6%
38.0%
78.4%
13.0%
75.2%
60.1%
50.0%
91.0%
18.8%
78.8%
57.1%
45.2%
92.1%

116
19.7%
59.4%
41.2%
23.3%
73.6%
8.9%
64.7%
55.6%
55.0%
91.7%
14.6%
72.3%
57.5%
47.7%
92.6%

117
21.9%
60.9%
33.9%
21.0%
73.9%
6.6%
65.7%
51.9%
48.9%
90.9%
13.7%
67.7%
42.7%
38.1%
91.3%

118
36.9%
62.2%
32.6%
23.6%
72.8%
30.6%
57.8%
43.7%
42.8%
88.9%
36.0%
64.7%
41.6%
35.0%
87.0%

119
20.1%
61.0%
40.2%
22.0%
72.1%
9.5%
60.1%
52.4%
50.9%
89.9%
13.4%
69.3%
53.8%
42.2%
89.9%

120
17.2%
57.7%
31.1%
27.5%
69.7%
8.1%
54.7%
49.1%
46.3%
88.9%
16.2%
62.6%
46.8%
43.8%
88.0%

121
23.7%
64.2%
33.5%
22.3%
74.9%
8.8%
62.9%
48.6%
44.7%
89.9%
14.0%
69.7%
45.2%
38.2%
90.2%

122
42.8%
64.9%
34.2%
22.8%
73.4%
27.4%
56.4%
42.3%
39.3%
86.0%
35.5%
64.5%
41.9%
34.7%
86.5%

123
32.3%
68.1%
44.1%
39.7%
76.9%
13.5%
70.4%
55.7%
49.7%
89.3%
18.4%
75.1%
57.0%
45.2%
89.8%

124
20.6%
63.3%
40.5%
22.0%
74.9%
10.1%
62.9%
54.2%
53.0%
88.4%
14.1%
68.7%
53.6%
42.6%
88.6%

125
20.7%
62.2%
36.1%
31.6%
73.4%
7.8%
54.0%
48.6%
44.7%
86.6%
14.9%
65.8%
46.1%
42.1%
88.4%

126
21.9%
65.6%
32.5%
24.2%
75.7%
8.0%
62.1%
46.1%
43.3%
88.9%
12.1%
70.2%
46.4%
39.1%
91.3%

127
37.7%
54.7%
29.7%
19.3%
65.5%
33.1%
63.6%
47.2%
29.1%
86.9%
38.5%
61.8%
36.3%
23.2%
86.9%

128
26.9%
60.6%
30.8%
25.0%
67.8%
9.9%
71.3%
42.6%
35.1%
87.4%
17.2%
72.2%
30.0%
19.6%
87.1%

129
22.2%
57.5%
36.0%
16.1%
68.9%
10.2%
64.9%
50.9%
30.7%
87.3%
15.7%
55.3%
37.0%
18.7%
86.9%

130
18.0%
59.6%
28.6%
29.3%
68.5%
6.4%
67.1%
41.2%
37.8%
88.1%
11.6%
61.8%
31.9%
30.6%
87.2%

131
22.8%
58.8%
29.2%
18.6%
69.1%
10.1%
72.8%
55.8%
31.2%
89.9%
18.9%
68.4%
44.2%
24.9%
89.3%

132
37.7%
46.3%
20.9%
11.7%
73.0%
24.9%
38.4%
23.4%
18.4%
85.6%
21.4%
36.1%
19.5%
13.6%
83.6%

133
18.9%
67.9%
18.6%
8.8%
75.2%
6.3%
69.6%
25.7%
13.9%
87.0%
9.1%
69.1%
17.8%
10.2%
85.4%

134
15.9%
65.6%
32.2%
6.9%
82.8%
7.6%
50.9%
46.2%
25.8%
91.1%
12.5%
46.3%
36.1%
15.6%
91.3%

135
11.8%
64.8%
17.6%
12.0%
74.4%
6.0%
50.4%
32.2%
32.6%
85.8%
11.4%
50.7%
24.9%
23.9%
85.7%

136
12.7%
70.0%
17.4%
6.1%
83.6%
6.1%
64.2%
47.6%
30.4%
92.5%
9.3%
49.9%
26.9%
16.0%
92.1%

137
39.9%
53.3%
21.5%
11.0%
75.0%
24.5%
48.1%
35.9%
26.6%
86.9%
26.6%
45.2%
27.9%
18.9%
88.2%

138
14.6%
58.3%
40.3%
9.7%
70.3%
8.4%
58.0%
47.4%
27.5%
85.4%
11.1%
49.3%
36.8%
17.2%
83.7%

139
10.7%
56.6%
17.0%
16.3%
76.2%
4.5%
53.9%
28.5%
25.4%
85.4%
7.5%
42.4%
17.3%
16.8%
83.2%

140
10.7%
61.0%
17.5%
7.0%
84.1%
9.1%
69.9%
43.5%
18.9%
89.3%
8.8%
57.9%
26.1%
12.3%
88.9%

141
46.2%
58.8%
25.8%
18.5%
77.8%
36.3%
56.4%
38.1%
23.4%
88.1%
27.9%
45.2%
23.2%
15.0%
87.0%

142
12.4%
66.7%
25.2%
17.8%
73.5%
8.4%
68.6%
28.6%
16.9%
83.7%
9.5%
61.8%
18.0%
11.7%
82.2%

143
14.3%
53.7%
37.8%
12.7%
68.9%
8.7%
54.5%
39.5%
20.4%
83.0%
10.5%
40.5%
24.3%
13.1%
78.5%

144
11.7%
58.2%
27.7%
32.0%
71.7%
7.7%
63.9%
30.6%
27.5%
86.3%
11.7%
48.9%
20.9%
20.4%
83.9%

145
15.8%
51.3%
24.1%
18.1%
72.0%
10.4%
62.8%
34.8%
21.8%
87.0%
12.9%
52.7%
24.2%
15.9%
84.5%

146
35.8%
44.6%
18.0%
18.3%
72.9%
35.3%
57.3%
41.1%
23.7%
88.3%
24.9%
38.9%
19.7%
12.6%
82.0%

147
18.1%
75.6%
24.1%
29.4%
81.9%
11.9%
76.2%
40.5%
21.3%
88.2%
10.3%
73.7%
20.8%
11.0%
87.9%

148
15.9%
50.8%
35.3%
15.5%
78.9%
16.0%
68.5%
58.0%
27.8%
90.2%
12.8%
48.6%
33.3%
14.7%
88.6%

149
14.5%
56.3%
23.2%
37.7%
78.2%
4.6%
63.9%
30.7%
27.2%
87.6%
9.0%
50.3%
19.4%
20.1%
86.7%

150
18.7%
58.3%
23.1%
17.9%
76.5%
7.3%
64.1%
44.8%
16.2%
89.9%
11.6%
58.1%
29.3%
14.5%
89.0%

151
42.2%
54.5%
18.6%
20.1%
74.1%
39.2%
60.2%
38.0%
23.5%
86.2%
31.1%
51.7%
26.9%
16.8%
85.4%

152
27.7%
72.0%
19.3%
21.3%
77.4%
16.8%
75.0%
35.4%
29.2%
87.5%
15.3%
76.7%
28.4%
17.2%
89.0%

153
19.2%
58.5%
32.4%
11.5%
74.2%
11.9%
62.4%
48.0%
22.1%
86.5%
13.3%
54.9%
37.0%
14.5%
84.5%

154
16.2%
69.1%
18.8%
35.5%
83.1%
6.9%
71.5%
32.7%
30.5%
90.7%
8.4%
65.3%
24.7%
24.5%
90.9%

155
22.0%
61.5%
17.3%
16.7%
85.3%
17.8%
71.7%
48.4%
20.0%
91.5%
12.6%
61.4%
32.8%
14.8%
91.5%

156
43.8%
49.2%
20.1%
16.0%
68.8%
42.6%
62.5%
39.7%
20.9%
86.7%
37.3%
54.2%
27.1%
16.8%
86.5%

157
30.4%
58.2%
21.6%
17.6%
67.5%
9.0%
65.6%
31.7%
21.6%
85.2%
17.2%
66.5%
25.5%
15.9%
85.5%

158
21.1%
62.4%
32.8%
9.7%
80.7%
13.1%
68.8%
59.6%
25.6%
89.0%
11.3%
53.3%
41.0%
13.3%
87.5%

159
19.2%
71.1%
20.8%
32.9%
82.7%
6.2%
69.9%
33.6%
31.6%
90.9%
10.0%
63.6%
23.2%
23.4%
90.8%

160
33.1%
56.9%
21.9%
16.3%
73.8%
8.1%
67.7%
44.7%
22.4%
89.3%
16.4%
60.2%
32.0%
16.4%
88.4%

161
39.8%
50.1%
19.8%
13.2%
64.5%
43.6%
63.8%
46.5%
24.4%
86.3%
35.5%
52.7%
27.8%
17.4%
83.3%

162
35.0%
63.4%
19.4%
15.6%
71.0%
25.0%
72.0%
37.1%
27.7%
86.2%
23.8%
70.3%
24.7%
14.3%
85.1%

163
18.6%
47.5%
24.6%
11.7%
68.9%
12.1%
64.1%
48.5%
22.6%
83.6%
13.7%
51.0%
30.4%
13.3%
82.5%

164
28.2%
58.2%
18.3%
20.0%
74.2%
6.0%
67.5%
31.1%
24.5%
88.3%
14.3%
51.1%
21.6%
17.4%
85.5%

165
29.8%
55.3%
20.2%
14.8%
70.6%
11.1%
64.5%
42.1%
16.3%
85.6%
14.9%
61.0%
29.9%
13.0%
85.4%

166
28.5%
58.5%
23.1%
17.7%
65.9%
20.1%
65.4%
36.3%
25.9%
83.1%
18.1%
64.0%
25.7%
15.6%
81.1%

167
21.3%
52.1%
25.1%
12.1%
64.3%
13.3%
61.6%
44.1%
24.6%
83.8%
16.7%
53.7%
31.9%
16.1%
83.5%

168
18.1%
60.1%
21.5%
18.8%
67.3%
6.1%
68.1%
35.2%
26.8%
86.4%
13.0%
60.4%
25.5%
19.8%
83.0%

169
21.2%
54.7%
20.3%
13.0%
65.5%
17.8%
65.6%
43.7%
17.9%
83.5%
17.7%
58.9%
29.0%
14.7%
81.9%

170
36.4%
55.7%
29.9%
14.9%
64.2%
27.6%
59.7%
40.8%
20.8%
83.9%
32.5%
59.8%
34.0%
17.5%
84.0%

171
32.5%
58.5%
33.4%
19.2%
65.8%
10.7%
62.3%
36.7%
26.3%
82.7%
19.4%
63.2%
27.7%
17.2%
80.7%

172
27.9%
57.3%
37.3%
12.7%
65.7%
10.7%
64.2%
51.5%
26.4%
84.2%
22.0%
59.2%
37.7%
17.2%
84.6%

173
21.5%
56.8%
24.6%
17.5%
65.4%
6.7%
57.7%
30.0%
22.8%
81.8%
14.0%
56.5%
24.9%
19.9%
80.9%

174
26.3%
56.2%
33.9%
14.0%
63.7%
9.3%
65.9%
52.0%
23.6%
84.7%
16.8%
62.3%
34.1%
15.6%
82.2%

175
41.1%
60.1%
38.8%
15.6%
66.8%
25.7%
56.0%
39.8%
24.7%
81.0%
36.1%
59.4%
34.3%
19.0%
80.5%

176
33.5%
56.2%
30.6%
16.3%
62.9%
9.5%
66.0%
42.0%
33.1%
84.1%
20.7%
62.7%
26.9%
16.2%
80.0%

177
23.3%
55.0%
34.9%
13.5%
65.5%
11.8%
61.0%
48.5%
32.2%
85.2%
19.1%
58.1%
40.3%
18.8%
85.0%

178
18.0%
54.2%
26.2%
19.1%
61.8%
6.9%
59.3%
35.5%
28.9%
80.6%
12.9%
54.9%
27.2%
22.2%
79.7%

179
28.6%
61.5%
37.1%
15.8%
69.6%
8.1%
65.8%
49.4%
27.1%
85.9%
19.0%
64.6%
38.9%
18.7%
86.7%

180
42.9%
60.9%
44.5%
20.6%
67.1%
27.6%
60.6%
45.8%
30.1%
83.7%
37.7%
62.9%
39.2%
23.1%
83.4%

181
36.7%
64.7%
45.1%
25.6%
71.1%
11.0%
67.9%
46.6%
40.8%
86.0%
22.0%
68.6%
35.0%
21.8%
84.5%

182
20.3%
52.9%
38.7%
15.7%
63.2%
8.9%
57.8%
44.4%
32.5%
82.4%
16.0%
55.0%
35.4%
19.3%
79.6%

183
17.4%
57.1%
30.5%
20.5%
64.5%
6.3%
58.1%
36.0%
31.8%
81.5%
15.0%
57.4%
30.9%
25.6%
81.4%

184
24.7%
57.5%
37.4%
17.6%
65.6%
6.6%
62.8%
46.7%
28.1%
82.3%
15.7%
60.2%
36.2%
18.8%
79.6%

185
39.7%
58.2%
41.4%
23.5%
65.7%
27.9%
58.4%
38.4%
33.9%
82.6%
36.8%
63.0%
39.7%
27.5%
83.0%

186
19.5%
57.3%
35.9%
25.9%
65.2%
5.3%
60.9%
37.8%
33.1%
82.7%
15.3%
59.5%
34.0%
30.2%
82.5%

187
44.1%
60.9%
44.7%
29.6%
67.5%
22.9%
58.9%
41.2%
32.3%
84.1%
35.2%
60.5%
35.2%
24.1%
83.1%

188
37.0%
64.7%
47.6%
40.8%
71.4%
10.4%
65.3%
38.1%
36.6%
87.1%
22.4%
65.9%
38.9%
29.4%
85.8%

189
25.3%
58.4%
43.9%
25.8%
66.4%
12.5%
65.5%
49.2%
33.1%
85.5%
19.8%
62.6%
40.2%
22.2%
85.1%

190
18.6%
55.4%
35.5%
27.0%
63.7%
6.2%
54.1%
36.6%
35.4%
79.9%
15.8%
58.1%
33.9%
29.3%
79.0%

191
22.7%
58.4%
37.4%
21.0%
66.6%
9.2%
66.8%
47.0%
35.8%
86.6%
17.0%
64.9%
38.4%
24.0%
85.3%

192
41.7%
58.9%
38.8%
29.3%
66.3%
28.4%
58.4%
38.1%
33.9%
86.2%
34.3%
62.7%
38.2%
25.3%
84.7%

193
36.1%
60.7%
45.3%
38.9%
68.4%
10.0%
69.7%
39.8%
37.4%
85.9%
19.8%
66.7%
32.0%
25.8%
83.4%

194
28.7%
63.4%
47.7%
25.9%
70.5%
9.8%
66.2%
54.1%
31.4%
89.9%
15.8%
68.2%
44.4%
21.9%
88.2%

195
34.4%
72.7%
55.4%
51.1%
76.9%
4.7%
64.1%
39.9%
40.1%
87.8%
19.9%
65.5%
35.0%
34.7%
84.7%

196
36.9%
68.3%
49.9%
34.6%
73.9%
9.2%
75.9%
58.8%
38.7%
90.6%
18.5%
67.9%
41.6%
25.2%
86.1%

197
40.7%
59.6%
40.5%
26.7%
66.0%
24.4%
53.7%
34.6%
31.6%
84.0%
33.2%
62.2%
37.8%
24.1%
84.8%

198
35.4%
59.6%
43.6%
36.7%
67.6%
10.6%
65.8%
42.4%
34.0%
85.9%
22.7%
66.6%
41.7%
32.6%
87.6%

199
27.7%
55.1%
38.8%
23.5%
63.7%
6.8%
56.5%
45.0%
37.3%
85.6%
19.5%
59.2%
37.0%
22.6%
81.9%

200
28.4%
60.3%
41.1%
36.8%
67.5%
8.7%
52.7%
33.8%
35.2%
83.3%
18.2%
60.7%
32.1%
29.7%
81.9%

201
25.0%
57.7%
40.7%
26.3%
65.0%
6.7%
62.2%
37.3%
30.3%
85.3%
15.5%
62.7%
37.2%
26.9%
82.6%

202
38.7%
58.7%
40.4%
25.0%
66.1%
28.1%
55.7%
37.1%
36.8%
86.7%
31.9%
64.6%
37.7%
25.8%
85.7%

203
28.1%
59.7%
45.5%
35.0%
66.4%
9.3%
63.9%
35.8%
28.9%
86.2%
18.6%
67.1%
37.5%
27.6%
87.9%

204
21.6%
56.7%
40.5%
20.6%
65.6%
7.3%
54.2%
39.8%
27.6%
84.7%
13.6%
59.5%
34.8%
19.7%
83.0%

205
18.2%
55.6%
33.6%
29.1%
62.2%
5.2%
49.5%
26.9%
28.8%
81.1%
12.4%
56.3%
26.9%
25.0%
77.5%

206
28.4%
67.6%
51.8%
30.2%
73.5%
4.4%
68.1%
44.9%
33.7%
88.8%
13.9%
68.5%
41.7%
24.4%
86.7%

207
46.3%
66.4%
51.6%
28.5%
72.5%
27.5%
51.4%
35.1%
39.0%
88.1%
39.1%
68.0%
40.8%
24.5%
86.6%

208
26.4%
63.2%
48.6%
40.3%
69.2%
9.4%
67.4%
33.3%
35.0%
85.3%
16.8%
68.1%
36.7%
32.5%
84.9%

209
19.2%
55.5%
41.6%
21.4%
63.9%
5.9%
51.3%
38.3%
22.3%
82.7%
12.0%
56.0%
33.9%
17.5%
78.0%

210
20.7%
59.2%
36.1%
30.5%
66.7%
6.3%
58.8%
34.5%
34.2%
85.6%
13.1%
61.5%
29.7%
25.5%
83.0%

211
17.9%
66.2%
50.4%
28.7%
72.1%
5.8%
66.9%
41.3%
36.8%
88.9%
13.9%
69.5%
41.6%
27.8%
88.2%

212
38.8%
58.6%
39.5%
23.9%
66.4%
22.0%
53.5%
36.9%
33.9%
86.1%
31.3%
64.3%
36.0%
23.4%
85.5%

213
23.9%
56.4%
42.7%
33.6%
62.6%
7.0%
61.2%
25.7%
24.0%
81.0%
12.9%
58.0%
26.4%
19.4%
77.3%

214
21.8%
62.1%
40.4%
32.4%
70.1%
5.7%
53.2%
30.3%
33.0%
87.3%
14.4%
62.8%
33.2%
29.9%
86.7%

215
18.6%
62.9%
46.6%
25.9%
69.3%
6.8%
64.0%
41.1%
30.4%
86.9%
12.8%
64.1%
37.2%
22.4%
83.8%

216
35.7%
59.5%
42.7%
25.2%
66.3%
22.4%
46.1%
28.1%
27.7%
84.0%
33.2%
59.4%
32.9%
24.0%
84.1%

217
24.1%
59.0%
45.4%
35.6%
66.3%
8.1%
70.0%
34.8%
30.8%
85.5%
14.0%
64.7%
30.2%
24.2%
80.9%

218
18.3%
55.2%
40.6%
20.4%
64.2%
9.1%
45.8%
33.2%
24.0%
83.6%
15.6%
56.8%
35.5%
18.8%
81.2%

219
16.3%
56.9%
35.9%
30.6%
64.3%
4.5%
47.9%
27.6%
28.9%
83.2%
13.2%
57.7%
29.3%
27.7%
82.9%

220
18.4%
59.8%
43.6%
23.7%
67.1%
6.6%
63.2%
41.5%
31.3%
84.4%
11.4%
62.3%
34.5%
21.8%
80.3%

221
40.9%
61.3%
43.6%
29.1%
68.1%
29.3%
53.3%
35.4%
34.1%
87.7%
37.2%
60.3%
36.4%
26.0%
87.3%

222
23.0%
60.2%
44.9%
33.3%
67.1%
9.3%
67.5%
33.9%
28.7%
84.2%
16.7%
66.3%
31.8%
21.8%
82.8%

223
17.5%
58.3%
33.8%
28.2%
66.3%
5.9%
56.3%
32.5%
32.4%
84.7%
12.5%
59.6%
30.7%
30.2%
86.5%

224
37.0%
58.4%
37.8%
24.7%
66.8%
30.2%
59.7%
40.5%
36.4%
88.7%
36.7%
61.1%
36.3%
27.7%
89.4%

225
32.3%
71.2%
54.3%
42.1%
76.5%
11.1%
82.0%
39.9%
42.8%
92.3%
16.2%
84.4%
32.2%
31.2%
92.7%

226
21.0%
58.7%
43.8%
21.8%
66.4%
7.5%
55.2%
42.2%
28.1%
84.8%
13.1%
54.9%
35.3%
18.4%
83.3%

227
17.7%
56.0%
33.7%
27.9%
64.8%
6.3%
57.3%
35.0%
35.8%
85.5%
11.8%
55.2%
30.4%
34.1%
84.9%

228
20.5%
59.1%
39.3%
23.7%
67.2%
7.6%
70.1%
46.9%
37.4%
89.6%
11.5%
69.3%
40.9%
31.9%
89.0%

229
50.1%
63.7%
35.1%
21.1%
70.5%
36.2%
55.1%
38.6%
29.2%
89.7%
43.5%
52.4%
30.7%
22.7%
88.1%

230
27.6%
58.6%
37.0%
24.9%
65.9%
13.8%
69.1%
39.4%
34.1%
86.6%
18.1%
69.9%
29.9%
21.2%
86.2%

231
21.4%
58.5%
41.4%
17.7%
67.6%
6.4%
59.6%
47.2%
32.8%
86.2%
14.0%
55.8%
38.2%
23.0%
85.5%

232
18.5%
59.2%
32.6%
28.5%
66.7%
7.8%
62.6%
38.3%
38.7%
87.1%
14.4%
58.4%
31.3%
33.2%
85.9%

233
20.3%
60.4%
38.0%
21.0%
67.6%
7.9%
69.5%
46.3%
35.8%
89.5%
11.8%
64.8%
38.3%
26.4%
87.8%

234
48.5%
61.6%
32.0%
18.9%
67.9%
21.3%
45.4%
28.9%
20.8%
85.0%
36.1%
49.3%
27.1%
17.8%
83.5%

235
42.9%
71.2%
44.1%
32.6%
76.2%
6.9%
80.6%
40.1%
29.5%
91.0%
15.2%
79.5%
27.4%
16.8%
89.3%

236
24.1%
58.4%
39.6%
16.2%
66.8%
14.1%
64.1%
50.1%
30.8%
86.0%
17.2%
59.8%
41.0%
18.5%
85.2%

237
28.7%
65.4%
37.7%
21.2%
72.5%
8.6%
76.0%
58.4%
38.2%
91.4%
16.4%
73.0%
45.1%
25.3%
91.2%

238
46.1%
63.0%
35.3%
19.3%
70.3%
33.3%
62.5%
46.1%
34.8%
88.9%
40.4%
63.0%
37.9%
23.4%
88.2%

239
26.8%
60.6%
41.4%
15.6%
68.5%
8.3%
64.9%
55.5%
37.2%
88.2%
13.5%
60.0%
42.3%
22.8%
85.7%

240
23.9%
59.5%
28.2%
25.0%
66.8%
6.0%
63.6%
40.1%
38.3%
87.3%
16.8%
61.1%
31.4%
28.3%
86.1%

241
25.7%
57.6%
32.1%
17.9%
65.2%
8.4%
71.9%
55.6%
34.0%
87.9%
19.2%
66.2%
44.3%
24.6%
84.8%

242
48.4%
66.0%
37.5%
22.2%
73.1%
34.4%
61.5%
44.7%
35.3%
90.6%
46.0%
67.8%
46.0%
30.7%
91.9%

243
37.9%
61.8%
33.8%
26.5%
68.7%
7.9%
68.0%
36.6%
28.5%
84.7%
26.1%
72.2%
35.0%
24.1%
86.4%

244
26.3%
56.5%
36.3%
15.3%
64.8%
13.1%
69.1%
57.5%
41.4%
88.7%
16.5%
62.1%
44.8%
22.0%
86.3%

245
22.5%
62.3%
31.6%
30.6%
69.1%
5.3%
59.5%
33.9%
32.9%
85.8%
10.8%
57.8%
28.3%
28.4%
85.2%

246
30.1%
64.4%
34.7%
18.8%
71.0%
8.3%
73.7%
55.7%
32.9%
88.2%
15.9%
70.8%
46.1%
23.0%
88.6%

247
41.3%
57.6%
29.1%
20.2%
67.5%
33.2%
64.8%
47.2%
29.3%
87.4%
42.3%
59.2%
33.5%
20.8%
86.2%

248
30.1%
62.5%
30.0%
25.6%
68.8%
14.8%
75.3%
44.6%
37.4%
88.1%
20.3%
72.2%
28.4%
20.0%
85.6%

249
22.8%
57.2%
36.5%
15.1%
69.0%
10.3%
70.4%
57.3%
35.6%
89.2%
16.5%
60.3%
42.2%
19.6%
88.6%

250
21.8%
60.0%
30.5%
29.9%
70.1%
4.8%
72.7%
42.6%
36.1%
88.2%
16.4%
64.8%
33.2%
28.0%
86.8%

251
23.0%
63.6%
30.9%
19.6%
73.3%
7.0%
77.0%
60.1%
28.4%
89.7%
19.3%
63.7%
37.6%
18.0%
88.9%

252
53.6%
68.5%
16.5%
5.0%
88.3%
20.0%
34.5%
27.0%
18.0%
92.8%
25.2%
35.5%
19.3%
12.5%
93.5%

253
16.3%
73.7%
17.5%
9.0%
79.2%
5.2%
73.6%
27.3%
17.2%
88.4%
9.7%
73.0%
18.8%
10.1%
88.4%

254
10.2%
62.0%
29.4%
4.3%
88.9%
5.6%
48.1%
46.6%
21.5%
92.8%
6.7%
33.2%
27.4%
9.9%
91.9%

255
12.8%
63.2%
14.8%
10.7%
79.4%
4.2%
44.3%
22.9%
24.0%
83.7%
9.4%
43.6%
20.1%
19.9%
85.7%

256
11.7%
68.0%
15.2%
6.2%
87.3%
3.7%
58.2%
36.5%
15.9%
92.4%
7.3%
42.9%
21.2%
11.1%
91.5%

257
41.8%
62.5%
22.0%
9.8%
74.5%
15.8%
50.4%
33.7%
20.1%
85.6%
21.0%
44.5%
22.2%
13.9%
85.9%

258
22.0%
64.4%
18.7%
10.8%
70.4%
7.3%
68.4%
40.9%
24.4%
86.0%
13.2%
70.3%
28.7%
15.9%
85.6%

259
18.4%
69.8%
33.0%
6.3%
81.3%
4.9%
57.1%
43.0%
15.7%
87.4%
9.0%
43.9%
28.5%
10.6%
87.3%

260
11.3%
75.6%
13.9%
11.4%
87.7%
3.7%
51.5%
21.5%
24.8%
89.4%
7.2%
44.9%
15.2%
17.7%
91.4%

261
15.4%
63.8%
17.3%
7.9%
79.4%
6.7%
65.5%
45.0%
23.8%
87.8%
9.2%
58.7%
33.1%
17.1%
88.8%

262
25.1%
60.0%
26.5%
14.9%
73.3%
27.9%
49.9%
34.4%
18.5%
83.4%
20.0%
41.4%
21.8%
13.8%
84.5%

263
19.7%
62.1%
19.0%
15.9%
71.0%
10.2%
66.7%
28.3%
20.0%
84.1%
14.0%
65.6%
21.0%
14.1%
83.8%

264
13.2%
70.9%
44.3%
10.3%
80.0%
5.4%
52.7%
42.1%
13.7%
86.1%
12.4%
42.9%
26.7%
12.3%
85.3%

265
12.0%
67.3%
30.9%
33.1%
77.3%
4.8%
64.4%
34.8%
27.0%
86.2%
10.1%
52.8%
21.8%
20.6%
85.5%

266
14.7%
63.2%
33.8%
22.7%
76.9%
9.2%
70.7%
50.1%
29.9%
86.3%
10.3%
57.5%
32.5%
20.9%
85.0%

267
39.7%
53.6%
23.6%
23.7%
70.9%
35.7%
50.9%
35.2%
23.9%
83.7%
29.8%
40.8%
23.8%
16.1%
80.1%

268
21.4%
67.5%
18.5%
18.6%
77.9%
6.4%
76.2%
35.2%
20.8%
89.2%
12.9%
71.1%
22.4%
12.6%
86.8%

269
15.9%
56.5%
42.9%
17.2%
74.6%
8.2%
56.0%
43.2%
16.3%
85.0%
12.2%
45.7%
29.7%
13.4%
84.9%

270
14.1%
63.1%
27.0%
44.3%
83.1%
9.4%
73.5%
39.9%
33.5%
92.0%
10.3%
59.4%
26.5%
26.1%
93.1%

271
19.1%
58.6%
32.6%
23.2%
75.0%
6.8%
70.6%
51.7%
20.8%
87.0%
11.8%
51.6%
25.5%
13.6%
82.6%

272
47.1%
43.3%
16.7%
15.8%
72.8%
37.3%
59.4%
41.4%
23.2%
87.0%
35.6%
44.2%
24.3%
14.2%
83.2%

273
27.5%
63.5%
20.5%
20.7%
72.3%
10.0%
67.1%
36.5%
24.6%
84.8%
15.7%
69.5%
27.2%
15.4%
85.1%

274
24.1%
48.6%
23.9%
9.3%
75.0%
7.6%
63.8%
51.2%
21.2%
87.7%
13.5%
43.6%
29.7%
11.7%
84.7%

275
16.2%
61.7%
22.3%
33.7%
75.5%
6.7%
61.9%
29.8%
25.0%
85.7%
11.7%
56.3%
22.0%
19.9%
86.3%

276
21.7%
62.8%
24.2%
19.0%
75.6%
8.4%
69.1%
46.2%
18.9%
86.3%
11.7%
65.2%
34.8%
14.2%
85.2%

277
41.2%
58.4%
25.0%
17.9%
69.5%
34.3%
60.0%
41.1%
25.0%
83.0%
35.5%
60.5%
34.5%
19.8%
86.2%

278
36.8%
64.1%
18.4%
17.0%
71.4%
28.5%
75.1%
41.5%
28.6%
87.9%
25.0%
72.6%
28.4%
17.3%
86.6%

279
21.1%
67.3%
20.0%
33.7%
82.9%
7.0%
74.8%
30.2%
26.2%
91.4%
10.5%
68.0%
24.7%
22.4%
90.3%

280
33.7%
64.5%
21.6%
16.5%
82.2%
7.6%
78.0%
53.9%
21.3%
93.5%
13.3%
67.0%
36.2%
14.1%
92.3%

281
43.6%
59.4%
23.2%
14.0%
68.3%
30.1%
60.1%
37.9%
20.2%
86.3%
34.2%
54.9%
27.8%
17.0%
85.0%

282
40.5%
65.3%
21.8%
17.0%
72.1%
7.5%
69.5%
31.6%
18.4%
85.5%
18.3%
72.9%
26.2%
14.3%
87.9%

283
27.3%
52.2%
23.6%
11.2%
68.5%
13.0%
65.8%
50.7%
25.3%
85.3%
17.6%
54.1%
33.6%
15.2%
83.2%

284
30.4%
55.0%
17.1%
19.2%
70.2%
5.1%
66.7%
30.9%
22.0%
86.7%
15.7%
50.9%
20.6%
15.8%
82.6%

285
31.1%
60.0%
23.5%
15.3%
70.1%
16.5%
71.5%
57.6%
27.5%
87.8%
21.7%
60.6%
33.4%
17.1%
85.2%

286
43.2%
58.8%
24.1%
14.4%
67.0%
41.2%
63.4%
45.9%
20.7%
82.6%
40.4%
58.9%
32.3%
16.9%
81.8%

287
40.0%
63.0%
31.7%
20.5%
68.8%
7.7%
68.3%
41.8%
27.2%
85.5%
20.8%
68.0%
27.6%
16.4%
83.7%

288
30.1%
55.5%
29.0%
12.5%
65.4%
8.1%
61.0%
45.3%
21.1%
81.2%
15.6%
52.6%
34.5%
14.9%
77.1%

289
26.4%
62.9%
22.3%
19.9%
70.4%
4.8%
65.8%
34.2%
24.0%
83.4%
16.0%
59.0%
26.5%
19.9%
84.7%

290
28.9%
59.7%
26.6%
17.2%
67.7%
7.9%
62.8%
42.6%
18.4%
82.6%
15.1%
63.6%
35.4%
15.8%
83.3%

291
52.8%
67.0%
31.1%
15.3%
73.6%
23.0%
55.1%
38.5%
18.9%
88.4%
40.9%
53.5%
29.7%
14.7%
88.6%

292
46.8%
68.6%
31.0%
18.4%
74.2%
7.9%
68.9%
40.3%
25.8%
86.2%
22.7%
71.1%
28.4%
15.4%
86.9%

293
29.1%
56.4%
35.0%
13.6%
65.0%
15.6%
63.1%
48.4%
27.6%
84.8%
20.8%
57.4%
36.8%
17.1%
81.9%

294
23.7%
60.3%
28.1%
20.4%
67.5%
6.8%
59.2%
29.1%
21.4%
81.2%
15.9%
58.9%
26.0%
20.0%
81.9%

295
29.2%
64.3%
36.8%
15.5%
71.6%
9.1%
70.2%
54.8%
26.2%
86.2%
16.6%
68.0%
39.5%
17.5%
86.5%

296
39.1%
54.5%
32.2%
14.3%
61.5%
20.3%
57.4%
44.1%
25.8%
78.2%
34.6%
55.7%
32.0%
17.4%
76.5%

297
34.9%
58.2%
41.2%
24.6%
64.5%
6.2%
64.6%
43.8%
35.9%
81.8%
21.2%
64.3%
35.1%
20.9%
81.5%

298
25.5%
56.5%
41.1%
15.5%
65.6%
8.5%
59.8%
44.4%
27.6%
82.6%
18.4%
59.1%
39.0%
17.9%
81.9%

299
27.6%
60.1%
39.3%
18.8%
67.3%
6.4%
64.4%
47.9%
28.4%
84.6%
17.4%
64.3%
39.7%
21.1%
84.7%

300
42.1%
61.8%
41.6%
18.9%
68.7%
13.2%
55.4%
38.0%
22.8%
83.9%
35.1%
60.6%
34.9%
19.1%
84.2%

301
34.1%
58.7%
44.6%
33.3%
65.1%
6.8%
65.7%
44.1%
33.3%
81.9%
19.4%
61.7%
32.1%
19.8%
77.4%

302
25.9%
57.5%
41.8%
16.5%
66.1%
7.3%
59.4%
44.4%
29.4%
83.4%
17.8%
60.7%
38.8%
18.9%
83.3%

303
20.9%
61.7%
34.9%
24.3%
68.5%
5.5%
59.4%
36.0%
28.4%
82.1%
15.3%
62.7%
34.8%
27.4%
82.4%

304
23.8%
60.5%
34.4%
14.6%
68.6%
6.6%
66.5%
52.9%
35.5%
84.1%
14.6%
64.8%
42.3%
22.1%
83.5%

305
44.8%
60.8%
44.7%
28.5%
67.6%
23.5%
58.2%
41.6%
32.5%
83.6%
38.7%
60.1%
38.8%
24.8%
80.9%

306
38.7%
58.9%
42.5%
32.2%
65.8%
5.6%
63.8%
42.4%
36.2%
83.4%
24.2%
63.8%
33.8%
22.7%
81.7%

307
27.4%
54.7%
37.5%
15.0%
63.3%
6.1%
56.5%
38.8%
29.6%
81.1%
19.9%
57.0%
37.4%
20.4%
80.3%

308
23.3%
56.9%
34.7%
26.8%
66.0%
5.1%
61.3%
33.5%
26.3%
82.0%
16.7%
60.6%
33.8%
26.1%
82.1%

309
30.4%
63.1%
46.3%
19.5%
69.8%
5.4%
63.0%
47.0%
27.2%
84.3%
18.9%
65.8%
42.5%
22.5%
84.6%

310
40.5%
57.4%
41.6%
26.2%
64.1%
26.3%
61.0%
42.0%
31.3%
82.4%
37.1%
62.4%
38.0%
23.6%
82.4%

311
39.2%
63.5%
51.6%
41.7%
70.2%
8.6%
67.8%
38.4%
38.9%
83.2%
24.2%
65.2%
32.4%
23.8%
82.0%

312
22.7%
54.0%
39.7%
18.6%
62.8%
9.4%
61.8%
45.6%
39.4%
86.0%
20.7%
63.2%
41.3%
25.4%
83.2%

313
25.2%
64.0%
45.5%
37.6%
71.3%
5.1%
63.6%
38.2%
34.9%
85.4%
19.4%
60.3%
34.9%
29.0%
83.5%

314
22.3%
60.3%
42.2%
19.6%
67.7%
5.4%
68.8%
49.2%
33.0%
86.1%
15.6%
60.8%
34.9%
21.2%
82.9%

315
44.3%
60.4%
41.2%
28.2%
67.0%
26.3%
68.7%
51.8%
36.2%
87.1%
42.0%
65.1%
40.9%
27.7%
84.2%

316
34.2%
57.0%
41.9%
35.4%
63.6%
12.5%
65.2%
35.3%
29.3%
82.5%
23.6%
62.1%
30.5%
23.4%
79.9%

317
26.3%
60.9%
42.4%
21.7%
67.9%
7.6%
66.6%
52.4%
34.0%
88.4%
19.7%
62.1%
38.6%
20.4%
85.7%

318
33.1%
60.9%
43.8%
39.2%
67.5%
4.3%
64.9%
37.0%
35.3%
84.2%
21.4%
57.6%
30.6%
27.7%
78.9%

319
30.0%
60.5%
43.7%
28.8%
68.0%
7.4%
69.9%
52.7%
36.4%
86.7%
20.6%
62.7%
36.3%
22.0%
82.7%

320
33.5%
59.6%
43.7%
36.2%
66.7%
5.9%
66.6%
38.4%
35.1%
85.1%
20.6%
65.0%
33.1%
26.3%
83.9%

321
33.4%
63.6%
49.6%
30.4%
71.0%
7.2%
67.4%
53.7%
43.5%
89.4%
21.8%
64.5%
41.4%
23.8%
86.3%

322
28.1%
61.1%
40.4%
36.0%
68.8%
5.1%
58.5%
36.3%
33.9%
85.6%
21.2%
62.5%
28.9%
25.9%
83.5%

323
35.2%
66.9%
47.7%
29.2%
73.7%
4.8%
71.1%
49.5%
33.3%
87.6%
19.8%
66.3%
37.1%
22.4%
85.5%

324
48.4%
64.6%
47.2%
29.3%
71.0%
18.7%
64.9%
45.7%
37.2%
87.5%
36.7%
65.3%
39.7%
25.7%
86.2%

325
33.1%
62.1%
46.3%
36.2%
69.5%
7.4%
70.5%
37.3%
34.7%
85.8%
18.1%
68.8%
34.0%
24.1%
86.0%

326
30.5%
64.7%
50.0%
26.5%
71.0%
8.5%
69.2%
54.9%
46.9%
88.6%
19.4%
67.9%
46.1%
26.1%
87.7%

327
25.0%
61.7%
42.5%
24.3%
69.7%
6.7%
67.2%
45.8%
28.7%
86.8%
15.6%
66.3%
38.4%
23.1%
85.8%

328
33.2%
67.5%
52.8%
42.1%
73.3%
5.4%
70.4%
35.0%
29.6%
86.6%
14.0%
69.0%
31.9%
21.5%
85.1%

329
25.3%
65.9%
53.4%
25.6%
73.1%
7.6%
67.9%
53.7%
32.9%
88.6%
12.8%
64.1%
44.2%
18.7%
86.1%

330
21.7%
62.1%
40.7%
33.5%
69.9%
5.1%
57.7%
30.1%
32.1%
86.0%
14.3%
63.6%
29.4%
25.5%
84.4%

331
21.1%
60.7%
44.7%
23.9%
67.2%
6.4%
66.5%
45.6%
29.1%
87.0%
13.6%
64.8%
38.6%
21.6%
84.8%

332
39.8%
59.5%
43.3%
26.8%
67.5%
31.9%
56.8%
38.0%
29.3%
88.6%
33.6%
62.7%
35.7%
20.0%
85.1%

333
27.9%
62.4%
49.0%
38.6%
69.0%
5.7%
69.6%
33.7%
30.0%
85.3%
14.7%
67.6%
34.0%
24.0%
84.2%

334
20.6%
58.4%
43.3%
18.9%
67.2%
11.4%
63.7%
48.8%
37.1%
88.3%
15.9%
62.9%
41.9%
21.5%
83.7%

335
19.9%
60.8%
39.7%
33.3%
68.5%
4.1%
53.2%
29.8%
26.7%
84.9%
12.7%
62.8%
32.8%
27.8%
85.6%

336
21.8%
66.2%
51.1%
33.4%
72.6%
4.1%
69.7%
49.1%
29.7%
87.6%
10.5%
66.7%
39.6%
24.2%
84.6%

337
37.2%
58.1%
40.2%
27.9%
66.1%
21.2%
53.1%
33.2%
37.0%
85.3%
30.6%
63.2%
39.6%
30.0%
84.9%

338
25.2%
59.2%
44.9%
35.3%
66.2%
5.4%
64.0%
24.3%
17.9%
81.1%
14.0%
64.8%
27.9%
18.5%
81.4%

339
18.9%
59.2%
45.1%
23.2%
66.8%
6.2%
54.8%
40.5%
21.8%
85.8%
13.0%
60.1%
41.3%
18.4%
85.8%

340
17.3%
56.5%
36.0%
28.6%
62.8%
5.0%
56.1%
29.8%
28.6%
84.5%
11.1%
61.0%
29.4%
25.7%
82.0%

341
18.3%
64.0%
42.4%
21.3%
71.3%
10.4%
73.7%
50.5%
37.8%
90.0%
15.1%
73.0%
45.1%
25.0%
88.0%

342
42.2%
64.7%
47.5%
30.5%
70.7%
11.8%
43.5%
28.1%
23.0%
88.6%
25.7%
61.9%
34.5%
20.4%
89.8%

343
29.6%
62.0%
46.0%
34.7%
68.3%
10.8%
73.1%
35.2%
33.6%
86.6%
16.7%
73.9%
33.9%
26.8%
86.6%

344
22.3%
57.8%
42.3%
18.6%
65.4%
10.9%
55.1%
39.7%
25.5%
84.7%
15.7%
58.8%
38.7%
17.5%
84.2%

345
15.6%
56.7%
35.8%
31.4%
64.0%
5.5%
55.2%
32.8%
33.4%
86.2%
12.9%
60.4%
32.1%
32.1%
84.9%

346
23.9%
62.6%
43.8%
25.8%
70.2%
5.5%
69.4%
45.4%
29.1%
90.4%
12.9%
67.2%
37.3%
21.3%
88.5%

347
41.8%
60.2%
37.3%
21.3%
67.3%
34.1%
61.2%
44.6%
31.8%
85.0%
40.3%
62.7%
37.7%
24.4%
86.9%

348
34.3%
64.3%
45.0%
36.3%
70.4%
6.8%
74.4%
44.6%
40.7%
87.8%
15.5%
72.6%
30.5%
22.8%
86.0%

349
23.2%
59.4%
41.1%
17.4%
68.8%
11.7%
65.8%
51.4%
35.9%
86.8%
18.2%
63.3%
45.5%
22.6%
87.4%

350
20.2%
60.7%
35.5%
31.9%
68.1%
4.6%
59.3%
32.9%
31.9%
84.7%
13.1%
58.4%
30.1%
33.4%
86.1%

351
21.5%
64.5%
44.5%
24.5%
70.8%
7.0%
71.5%
49.8%
32.4%
88.7%
13.9%
67.6%
39.6%
23.3%
88.9%

352
55.5%
69.3%
42.4%
25.4%
74.4%
21.8%
54.3%
37.6%
28.4%
90.7%
41.5%
51.2%
29.8%
21.2%
90.7%

353
33.5%
60.6%
43.9%
33.6%
66.0%
5.6%
72.3%
39.7%
34.8%
86.1%
16.5%
71.9%
30.2%
21.8%
83.6%

354
17.8%
58.4%
33.6%
29.5%
67.4%
8.1%
63.3%
44.5%
41.3%
89.5%
14.3%
67.0%
40.2%
38.5%
90.9%

355
22.8%
60.5%
36.4%
20.8%
68.0%
7.6%
69.8%
51.8%
33.3%
87.4%
13.9%
63.7%
37.6%
22.5%
84.2%

356
52.7%
67.2%
40.9%
23.0%
73.3%
23.8%
66.6%
52.0%
38.7%
93.1%
54.1%
68.2%
43.7%
27.1%
92.8%

357
41.8%
69.1%
38.7%
30.2%
74.4%
9.6%
87.9%
49.9%
45.2%
94.4%
18.8%
85.3%
32.8%
23.4%
92.7%

358
32.7%
72.2%
54.9%
15.9%
77.4%
7.4%
59.6%
51.6%
24.9%
88.9%
14.7%
52.0%
40.8%
16.3%
86.9%

359
25.4%
71.8%
35.2%
36.1%
77.2%
4.3%
52.6%
27.0%
27.2%
85.8%
11.9%
50.4%
21.6%
23.8%
84.5%

360
27.2%
61.9%
35.8%
18.9%
68.4%
7.9%
72.1%
55.6%
33.4%
88.2%
17.6%
67.4%
40.0%
22.5%
86.5%

361
46.9%
63.4%
34.6%
18.8%
69.4%
40.4%
68.5%
52.8%
39.1%
91.7%
44.4%
64.5%
41.4%
22.8%
86.7%

362
35.7%
67.7%
48.1%
16.1%
75.1%
19.1%
75.1%
64.9%
42.4%
91.7%
24.5%
69.4%
54.9%
24.4%
89.6%

363
23.9%
63.6%
33.7%
30.3%
71.3%
6.4%
70.1%
45.7%
40.6%
89.5%
16.6%
64.4%
36.0%
33.6%
86.8%

364
39.3%
71.3%
36.7%
19.5%
77.7%
4.3%
78.5%
60.7%
29.7%
91.1%
24.5%
70.3%
46.1%
20.1%
89.4%

365
50.6%
62.5%
35.9%
20.2%
68.9%
45.1%
66.1%
47.7%
34.6%
87.2%
52.8%
71.2%
49.1%
30.2%
88.0%

366
41.2%
66.9%
36.5%
31.1%
72.6%
4.8%
71.3%
34.6%
24.9%
86.6%
17.4%
78.1%
29.0%
17.7%
89.9%

367
33.2%
69.1%
48.9%
18.5%
75.0%
16.3%
72.1%
59.8%
34.8%
89.7%
18.6%
67.3%
52.6%
23.3%
90.1%

368
26.7%
68.4%
36.3%
35.8%
74.5%
3.3%
64.9%
35.3%
35.8%
90.0%
11.2%
60.0%
27.6%
31.0%
90.6%

369
37.8%
70.3%
37.8%
19.5%
76.5%
4.7%
77.4%
63.0%
32.3%
89.6%
24.3%
74.6%
52.0%
21.9%
90.8%

370
46.9%
62.4%
32.4%
20.0%
73.0%
29.1%
60.7%
43.6%
33.9%
90.3%
44.5%
56.0%
34.8%
23.3%
89.9%

371
35.5%
68.3%
35.1%
26.3%
74.9%
15.5%
76.6%
53.0%
46.9%
89.1%
21.7%
75.6%
40.2%
28.7%
87.8%

372
24.4%
58.2%
35.7%
15.0%
68.7%
16.5%
74.0%
62.7%
45.6%
89.4%
20.0%
63.8%
47.4%
25.3%
86.6%

373
22.9%
62.1%
30.6%
30.2%
70.5%
5.0%
73.0%
49.2%
44.0%
90.3%
17.2%
63.3%
33.6%
32.0%
88.1%

374
26.2%
62.7%
31.4%
20.8%
72.3%
8.4%
77.8%
65.8%
37.5%
91.0%
20.2%
68.1%
46.2%
22.9%
88.9%

375
55.0%
73.2%
18.8%
5.5%
87.3%
26.5%
48.6%
36.2%
23.7%
91.9%
36.8%
45.7%
28.0%
16.0%
92.7%

376
28.2%
72.4%
22.3%
10.3%
78.0%
5.4%
63.8%
21.5%
14.4%
83.4%
12.9%
66.9%
22.6%
16.0%
84.1%

377
15.8%
64.0%
31.9%
7.9%
76.9%
4.8%
45.5%
34.7%
16.9%
83.6%
10.5%
43.3%
29.7%
12.4%
85.0%

378
13.0%
66.9%
14.9%
10.2%
80.1%
4.3%
43.3%
25.4%
29.5%
85.8%
9.4%
42.5%
21.0%
22.5%
87.5%

379
20.5%
58.9%
21.6%
9.6%
75.7%
5.3%
52.0%
37.8%
26.8%
87.3%
12.6%
58.3%
42.7%
26.9%
87.9%

380
42.0%
59.8%
26.1%
11.9%
80.1%
24.6%
70.5%
42.0%
37.7%
89.3%
30.5%
63.3%
32.8%
27.9%
89.4%

381
21.8%
72.0%
27.0%
12.5%
78.1%
7.0%
68.8%
29.1%
18.1%
85.7%
11.9%
70.7%
21.9%
12.8%
86.1%

382
19.5%
71.9%
31.9%
6.2%
84.0%
12.0%
64.4%
52.9%
22.0%
88.0%
14.3%
55.1%
41.8%
15.3%
90.2%

383
10.6%
74.2%
12.4%
10.1%
88.0%
3.6%
67.5%
30.5%
24.6%
89.5%
7.6%
58.8%
20.3%
19.2%
90.3%

384
41.1%
68.8%
34.1%
15.5%
78.1%
25.4%
60.2%
38.5%
19.3%
88.0%
23.8%
47.6%
23.1%
13.2%
86.6%

385
24.8%
66.8%
21.8%
17.3%
74.0%
5.8%
65.1%
24.1%
15.7%
83.7%
12.1%
67.7%
20.6%
11.8%
84.6%

386
14.5%
62.5%
42.2%
11.4%
74.5%
9.4%
65.4%
48.9%
29.7%
84.9%
12.4%
56.3%
39.5%
20.0%
84.9%

387
11.7%
66.1%
28.7%
43.4%
84.5%
5.1%
62.8%
32.3%
34.4%
91.5%
8.0%
53.4%
21.0%
25.8%
90.6%

388
13.1%
64.6%
31.3%
14.4%
77.7%
5.0%
58.0%
37.7%
20.7%
88.9%
11.9%
44.0%
22.0%
14.2%
86.8%

389
33.5%
63.3%
39.7%
25.0%
82.1%
42.6%
50.5%
29.6%
17.8%
89.5%
30.0%
34.7%
17.7%
12.0%
86.7%

390
28.8%
64.0%
14.6%
14.9%
80.2%
14.1%
80.3%
42.6%
39.1%
90.4%
13.8%
76.1%
25.3%
19.5%
88.6%

391
13.6%
62.9%
51.0%
22.2%
75.6%
9.4%
64.2%
51.5%
22.3%
87.6%
13.0%
53.0%
34.3%
14.6%
84.9%

392
12.4%
66.0%
39.0%
44.8%
77.7%
5.1%
71.2%
34.6%
28.6%
87.9%
10.4%
56.7%
23.3%
24.0%
86.5%

393
42.6%
73.8%
19.6%
13.3%
88.9%
12.6%
73.8%
53.1%
16.6%
94.0%
17.8%
66.2%
38.7%
12.4%
93.7%

394
53.2%
57.5%
19.1%
18.9%
82.0%
66.9%
65.5%
42.6%
19.3%
89.5%
61.6%
51.8%
27.5%
14.4%
89.5%

395
27.0%
69.7%
17.6%
16.1%
77.8%
31.9%
76.9%
35.9%
22.4%
89.0%
22.9%
76.7%
26.3%
14.7%
89.1%

396
22.7%
60.1%
28.5%
9.7%
73.9%
8.3%
56.1%
45.9%
19.8%
83.7%
14.4%
48.3%
35.6%
12.4%
82.4%

397
14.6%
62.9%
23.8%
37.1%
77.5%
6.7%
70.3%
43.9%
36.0%
87.5%
10.5%
57.5%
26.3%
26.6%
84.8%

398
22.5%
60.2%
24.6%
23.0%
76.3%
9.5%
70.4%
49.1%
19.2%
87.1%
13.3%
70.2%
37.7%
16.5%
88.6%

399
45.3%
57.7%
21.4%
16.2%
69.0%
33.0%
61.8%
38.6%
23.0%
85.1%
34.9%
59.6%
33.6%
19.4%
84.9%

400
31.1%
61.2%
20.2%
18.6%
69.4%
10.4%
65.7%
38.8%
30.5%
82.7%
18.7%
66.7%
28.9%
18.5%
84.1%

401
28.8%
47.7%
27.4%
12.8%
70.7%
10.9%
62.9%
49.6%
21.6%
85.9%
15.9%
49.2%
30.7%
14.2%
83.1%

402
20.9%
56.2%
21.4%
30.9%
72.9%
6.9%
73.8%
35.6%
25.2%
88.3%
13.2%
65.2%
25.0%
20.4%
86.2%

403
37.8%
46.8%
18.9%
12.2%
65.3%
25.3%
59.4%
38.3%
21.0%
84.1%
26.6%
50.5%
26.3%
15.5%
80.0%

404
37.3%
63.7%
24.9%
18.1%
70.3%
10.6%
68.1%
39.9%
27.2%
83.4%
18.4%
68.5%
31.0%
16.2%
84.3%

405
35.7%
48.4%
25.8%
11.1%
70.0%
10.8%
68.3%
54.9%
30.1%
85.6%
19.0%
48.1%
31.3%
14.1%
80.8%

406
32.1%
59.1%
19.6%
20.1%
72.4%
5.7%
72.6%
38.0%
24.3%
87.9%
16.6%
59.6%
23.3%
17.5%
84.5%

407
35.1%
56.4%
20.4%
13.0%
72.5%
8.6%
69.6%
56.2%
25.1%
88.0%
16.6%
58.2%
34.2%
14.7%
85.1%

408
51.8%
64.0%
28.2%
15.1%
70.8%
42.9%
64.2%
37.2%
16.8%
83.2%
46.2%
58.8%
28.3%
14.2%
82.0%

409
37.4%
61.8%
25.7%
14.2%
69.4%
44.0%
66.9%
32.9%
18.4%
83.7%
42.9%
69.2%
28.9%
15.2%
84.6%

410
29.4%
57.5%
31.4%
14.8%
70.3%
7.5%
56.3%
38.0%
19.2%
84.8%
17.9%
56.0%
34.6%
15.5%
86.9%

411
33.1%
69.1%
26.8%
15.9%
75.6%
7.6%
72.4%
58.7%
21.8%
86.9%
17.7%
70.2%
45.4%
15.6%
86.2%

412
41.4%
58.4%
32.7%
17.7%
66.4%
23.9%
58.5%
45.0%
22.8%
83.1%
39.0%
61.3%
36.4%
18.6%
83.8%

413
35.3%
57.0%
25.8%
16.5%
64.1%
6.7%
63.1%
34.6%
25.2%
80.6%
18.7%
60.2%
23.3%
14.4%
76.3%

414
31.1%
58.4%
35.5%
12.5%
67.1%
6.6%
63.0%
50.1%
23.8%
82.8%
18.8%
59.3%
39.4%
16.0%
82.7%

415
23.6%
57.9%
26.2%
19.0%
65.7%
6.5%
62.8%
34.8%
22.0%
83.3%
17.1%
62.1%
27.4%
20.5%
82.4%

416
32.0%
73.3%
34.4%
13.6%
79.2%
5.5%
64.6%
48.1%
26.3%
86.5%
17.0%
61.2%
35.3%
18.2%
87.1%

417
40.1%
56.8%
31.6%
13.2%
65.3%
33.8%
63.5%
46.3%
26.5%
81.6%
34.1%
61.0%
34.4%
17.2%
80.5%

418
35.3%
62.1%
44.1%
23.4%
68.6%
10.6%
64.7%
45.4%
37.0%
83.7%
26.0%
65.0%
37.2%
22.6%
82.4%

419
27.6%
57.7%
39.1%
16.1%
65.9%
8.2%
60.5%
43.6%
27.3%
83.4%
20.2%
59.6%
37.2%
16.8%
81.2%

420
24.3%
59.6%
26.6%
17.8%
68.4%
6.2%
65.6%
42.0%
30.8%
82.9%
15.7%
62.3%
32.3%
24.2%
81.6%

421
31.2%
62.5%
36.8%
14.4%
69.8%
8.3%
66.3%
54.2%
30.4%
84.8%
20.8%
65.7%
42.4%
20.6%
84.5%

422
44.4%
61.6%
44.5%
19.8%
69.1%
17.0%
49.4%
32.3%
25.8%
81.3%
34.1%
55.8%
33.1%
21.3%
82.1%

423
39.0%
63.6%
48.3%
32.1%
70.1%
11.1%
65.3%
47.8%
44.2%
83.7%
22.2%
68.3%
46.9%
37.4%
84.4%

424
28.5%
57.9%
44.3%
19.9%
68.0%
5.6%
49.5%
36.9%
22.4%
81.6%
18.6%
54.8%
37.0%
18.1%
80.8%

425
21.9%
61.7%
32.9%
23.4%
70.0%
5.6%
64.4%
41.4%
29.8%
82.6%
15.3%
67.3%
35.0%
25.6%
84.3%

426
23.3%
58.6%
39.1%
16.3%
66.5%
15.7%
61.7%
44.4%
28.6%
82.4%
23.2%
65.0%
43.2%
20.9%
83.1%

427
45.4%
62.8%
45.8%
22.2%
70.5%
34.4%
64.0%
48.2%
37.5%
86.1%
44.1%
68.9%
48.3%
29.9%
85.7%

428
38.3%
62.1%
45.7%
36.7%
68.2%
8.0%
67.3%
48.1%
45.5%
84.0%
25.3%
64.5%
40.3%
31.1%
81.6%

429
24.5%
54.1%
40.5%
15.9%
62.1%
7.7%
63.4%
50.0%
39.2%
83.0%
20.7%
61.7%
42.5%
20.7%
81.3%

430
22.2%
58.9%
35.2%
26.2%
66.6%
6.9%
62.8%
40.0%
30.5%
83.4%
20.3%
64.0%
34.6%
26.3%
82.7%

431
27.3%
59.6%
42.4%
25.5%
67.1%
11.4%
68.6%
54.6%
31.0%
84.9%
23.9%
67.5%
46.2%
24.9%
84.0%

432
41.2%
57.1%
41.9%
27.9%
64.2%
17.0%
61.4%
44.5%
33.9%
83.2%
35.9%
61.7%
41.1%
24.7%
80.2%

433
37.4%
64.1%
48.2%
35.9%
69.8%
15.1%
76.4%
56.5%
55.2%
88.7%
28.2%
72.2%
47.4%
37.1%
87.2%

434
28.5%
61.3%
46.4%
30.3%
69.6%
10.0%
56.7%
41.6%
41.3%
83.9%
21.0%
61.8%
40.6%
34.2%
83.3%

435
23.7%
60.3%
40.1%
31.7%
67.9%
5.6%
66.9%
43.6%
36.7%
86.8%
19.3%
64.2%
36.7%
29.2%
83.8%

436
31.2%
62.8%
48.0%
29.8%
70.4%
4.7%
56.9%
36.2%
28.9%
84.1%
21.5%
57.1%
32.0%
21.4%
82.7%

437
44.6%
60.5%
45.0%
31.5%
66.7%
25.2%
66.0%
49.0%
36.8%
85.9%
38.9%
63.5%
38.3%
22.5%
82.7%

438
40.4%
63.4%
47.4%
41.9%
69.3%
5.7%
73.3%
42.9%
35.7%
87.8%
23.6%
65.6%
29.7%
20.2%
82.6%

439
35.9%
62.2%
49.1%
30.0%
69.1%
5.9%
58.7%
48.9%
33.0%
85.4%
21.2%
57.4%
32.2%
16.5%
79.8%

440
29.1%
59.0%
39.9%
35.1%
65.6%
4.5%
68.8%
45.0%
40.8%
85.5%
20.7%
64.8%
32.6%
28.6%
82.0%

441
36.0%
63.2%
45.5%
31.2%
70.3%
5.7%
68.9%
55.9%
34.1%
86.9%
28.0%
66.8%
41.7%
21.2%
83.8%

442
40.6%
58.1%
40.9%
27.3%
65.4%
38.8%
67.8%
50.3%
36.2%
87.0%
37.6%
65.5%
42.5%
29.4%
84.6%

443
36.3%
58.3%
43.8%
37.1%
64.4%
25.4%
66.5%
38.4%
36.3%
83.9%
27.3%
62.4%
36.3%
29.2%
78.8%

444
31.6%
62.0%
47.0%
28.6%
69.0%
8.2%
66.3%
53.0%
39.5%
85.7%
23.0%
65.7%
41.9%
20.8%
83.9%

445
27.0%
57.1%
38.9%
34.1%
64.3%
5.7%
43.6%
24.3%
25.6%
80.4%
14.4%
49.5%
22.8%
20.4%
76.1%

446
26.2%
58.9%
41.8%
29.0%
66.0%
7.2%
63.9%
43.4%
33.6%
81.5%
17.3%
63.6%
41.4%
27.5%
79.4%

447
39.5%
60.3%
42.3%
27.0%
67.1%
23.2%
63.9%
44.5%
35.9%
85.4%
35.0%
65.5%
38.1%
23.4%
82.8%

448
36.2%
62.8%
48.5%
41.8%
68.7%
5.9%
76.7%
53.8%
54.6%
88.5%
19.2%
69.0%
41.6%
32.5%
83.7%

449
24.7%
56.5%
42.7%
22.6%
64.8%
6.8%
58.5%
47.7%
31.3%
85.1%
17.1%
59.3%
36.6%
18.2%
80.1%

450
22.1%
59.6%
39.6%
34.1%
66.8%
5.8%
73.4%
45.3%
38.3%
88.4%
14.2%
67.5%
35.1%
28.0%
84.7%

451
21.5%
54.5%
36.5%
22.6%
64.2%
7.5%
67.5%
52.5%
35.1%
84.7%
14.2%
57.6%
35.0%
22.8%
78.9%

452
44.3%
62.3%
47.0%
27.2%
68.2%
27.0%
53.8%
37.8%
36.7%
87.6%
39.2%
67.4%
44.5%
24.5%
84.6%

453
36.4%
66.0%
51.2%
41.9%
72.3%
7.4%
73.5%
37.8%
32.9%
87.7%
18.6%
69.7%
36.1%
25.3%
85.3%

454
23.7%
61.6%
46.3%
24.3%
68.4%
10.8%
69.1%
54.0%
43.2%
86.8%
17.6%
66.5%
44.5%
23.8%
84.5%

455
24.6%
70.8%
48.7%
42.3%
76.0%
3.9%
65.5%
40.5%
41.3%
89.9%
11.6%
69.4%
33.8%
32.3%
88.2%

456
21.5%
57.2%
39.8%
22.8%
64.8%
5.4%
55.2%
35.1%
21.6%
81.8%
13.2%
59.9%
33.0%
17.1%
79.2%

457
44.5%
65.9%
49.4%
29.1%
72.2%
20.7%
51.9%
31.9%
27.1%
89.6%
35.6%
66.2%
38.6%
22.7%
87.6%

458
27.4%
63.2%
48.5%
37.7%
69.6%
8.9%
76.1%
49.8%
49.2%
88.2%
15.6%
73.1%
42.5%
34.0%
86.5%

459
22.1%
63.3%
50.9%
27.2%
70.1%
13.4%
76.1%
65.5%
55.7%
91.7%
18.3%
68.5%
47.2%
29.5%
84.9%

460
21.3%
58.7%
36.7%
29.9%
66.2%
6.7%
61.7%
41.4%
38.4%
85.1%
15.0%
60.6%
30.9%
25.4%
80.0%

461
22.0%
62.7%
44.5%
25.6%
70.0%
7.6%
72.4%
53.7%
35.6%
87.8%
16.4%
70.8%
45.3%
24.9%
88.3%

462
39.6%
62.0%
43.2%
23.5%
68.1%
32.0%
62.8%
39.8%
32.7%
86.6%
37.4%
67.8%
42.9%
25.9%
84.6%

463
25.9%
58.1%
42.6%
31.8%
65.3%
19.0%
70.5%
39.1%
38.7%
84.3%
23.5%
71.0%
36.8%
32.0%
84.1%

464
20.9%
59.2%
46.8%
25.4%
66.9%
5.8%
61.9%
51.2%
34.8%
86.5%
14.4%
65.1%
46.4%
21.8%
84.0%

465
15.2%
61.3%
39.0%
31.5%
68.4%
6.1%
68.9%
36.8%
36.7%
86.6%
12.2%
71.1%
35.4%
32.2%
85.3%

466
19.0%
62.6%
43.9%
23.1%
69.0%
5.7%
73.4%
51.4%
37.6%
88.3%
12.8%
72.6%
46.3%
27.4%
86.5%

467
42.4%
61.2%
42.4%
25.5%
68.3%
24.4%
61.6%
47.6%
45.7%
88.6%
38.5%
65.2%
44.7%
29.6%
86.5%

468
26.6%
64.6%
50.2%
39.1%
70.8%
11.4%
75.1%
44.7%
44.3%
87.7%
16.9%
71.0%
40.3%
32.4%
84.1%

469
22.2%
60.5%
44.0%
21.9%
68.3%
5.8%
43.2%
33.2%
21.2%
83.3%
15.3%
56.3%
34.0%
16.3%
83.9%

470
17.5%
61.0%
40.2%
33.2%
68.4%
4.7%
71.3%
44.1%
43.0%
89.3%
11.3%
67.7%
36.7%
36.1%
86.9%

471
22.6%
63.9%
48.4%
28.6%
70.1%
4.8%
72.6%
55.2%
37.9%
88.1%
14.4%
68.9%
46.4%
26.9%
86.9%

472
44.7%
60.6%
41.8%
23.1%
67.2%
46.7%
69.3%
50.3%
36.2%
88.9%
52.4%
67.4%
44.9%
31.1%
86.9%

473
35.4%
63.9%
42.0%
32.6%
70.8%
12.1%
74.0%
45.0%
39.2%
88.0%
23.8%
74.5%
34.5%
25.8%
87.4%

474
24.6%
58.0%
42.3%
21.0%
66.3%
7.0%
58.3%
48.0%
31.6%
85.0%
15.6%
54.7%
40.8%
22.3%
83.6%

475
20.4%
58.0%
36.7%
32.2%
65.3%
5.3%
60.3%
40.8%
40.7%
86.9%
14.4%
61.6%
36.8%
38.4%
85.7%

476
23.0%
61.2%
41.7%
20.6%
67.2%
9.7%
75.4%
56.3%
35.8%
89.4%
18.2%
73.5%
47.9%
27.6%
87.9%

477
46.9%
62.0%
38.9%
22.8%
68.5%
14.5%
38.3%
23.9%
22.7%
84.5%
31.3%
40.7%
23.0%
18.0%
81.7%

478
39.1%
64.0%
36.6%
30.1%
69.1%
4.7%
73.8%
34.4%
26.3%
86.8%
17.4%
74.2%
23.9%
16.7%
86.2%

479
24.9%
60.0%
43.4%
18.6%
67.9%
9.0%
74.2%
56.5%
43.3%
89.3%
17.1%
69.4%
48.6%
28.8%
87.3%

480
22.8%
66.0%
35.9%
32.4%
72.1%
4.4%
80.7%
51.2%
45.9%
92.0%
14.6%
75.6%
41.6%
40.9%
90.3%

481
26.8%
61.4%
38.9%
21.9%
67.7%
6.5%
74.1%
58.4%
38.3%
89.0%
19.3%
69.8%
48.0%
30.3%
88.7%

482
53.1%
66.9%
39.0%
20.4%
73.5%
60.9%
64.5%
48.3%
27.2%
89.7%
63.4%
67.5%
45.2%
26.5%
90.2%

483
46.4%
74.1%
47.6%
37.6%
78.9%
11.7%
86.8%
56.2%
56.5%
93.5%
21.3%
83.7%
41.2%
37.7%
91.6%

484
31.2%
62.4%
42.4%
15.2%
69.1%
5.8%
78.0%
64.5%
45.7%
91.8%
17.9%
71.2%
51.3%
26.7%
89.3%

485
25.2%
67.5%
34.5%
33.3%
74.1%
4.5%
74.2%
46.7%
44.0%
90.0%
16.2%
72.1%
39.9%
40.7%
89.8%

486
43.1%
80.6%
45.8%
22.8%
84.9%
5.5%
66.6%
47.2%
24.9%
87.8%
19.1%
63.6%
38.6%
21.4%
88.7%

487
50.6%
65.2%
37.2%
22.6%
71.5%
25.9%
67.5%
48.7%
53.8%
91.1%
47.3%
70.9%
47.7%
41.1%
88.8%

488
46.1%
67.8%
35.6%
28.2%
73.1%
7.0%
76.4%
48.8%
42.2%
89.4%
28.1%
73.0%
35.0%
23.6%
86.1%

489
34.4%
66.6%
45.9%
14.9%
73.9%
18.2%
78.8%
68.8%
45.1%
92.3%
22.8%
71.8%
57.7%
26.1%
88.0%

490
27.4%
65.8%
30.8%
27.9%
73.4%
6.9%
61.8%
41.0%
41.2%
88.8%
15.3%
54.4%
28.8%
28.8%
82.1%

491
32.7%
65.6%
37.1%
20.5%
71.8%
4.6%
77.9%
61.7%
37.2%
90.2%
19.4%
77.4%
52.4%
27.6%
91.2%

492
48.5%
63.3%
35.8%
20.7%
69.4%
24.1%
61.5%
48.3%
36.3%
88.4%
46.7%
63.6%
40.5%
24.0%
86.5%

493
45.6%
66.6%
38.7%
31.8%
72.2%
13.4%
79.1%
56.9%
56.6%
90.1%
29.3%
79.0%
48.7%
41.8%
89.5%

494
43.3%
76.1%
54.5%
16.1%
81.2%
6.9%
68.0%
62.4%
30.1%
92.6%
22.6%
62.0%
55.6%
18.4%
92.0%

495
28.8%
70.9%
34.0%
33.4%
76.8%
4.6%
73.7%
46.8%
38.7%
87.8%
20.2%
73.9%
40.5%
34.5%
88.3%

496
39.3%
71.1%
36.6%
20.2%
76.1%
5.4%
72.7%
59.2%
32.1%
89.2%
23.9%
72.0%
51.8%
25.1%
89.6%

497
43.7%
59.9%
30.0%
19.6%
69.4%
36.2%
65.2%
47.9%
36.0%
89.3%
48.1%
61.9%
36.4%
26.4%
87.3%

498
34.1%
61.4%
30.2%
26.1%
68.2%
8.0%
73.5%
44.6%
37.2%
88.4%
31.2%
73.3%
34.1%
23.8%
86.8%

499
24.7%
58.5%
34.5%
15.6%
69.4%
13.7%
72.0%
61.7%
46.9%
89.5%
21.8%
63.8%
45.6%
26.1%
87.3%

500
21.1%
61.4%
30.9%
30.8%
69.7%
5.8%
72.3%
52.7%
50.5%
90.7%
15.9%
67.9%
41.4%
40.7%
89.0%

501
26.1%
60.1%
31.4%
20.3%
69.7%
6.0%
71.5%
54.4%
31.6%
88.6%
21.2%
66.5%
40.0%
23.9%
88.5%

502
52.1%
64.2%
20.3%
8.5%
77.4%
14.9%
29.9%
22.3%
20.5%
87.9%
26.0%
35.9%
20.6%
14.4%
87.0%

503
21.0%
71.2%
25.6%
10.5%
77.0%
5.8%
70.7%
21.2%
14.8%
86.9%
13.2%
69.7%
20.9%
13.5%
88.5%

504
15.8%
54.1%
33.6%
8.6%
79.6%
4.0%
29.3%
24.1%
13.7%
85.9%
12.4%
36.2%
26.3%
12.9%
88.4%

505
9.1%
80.1%
11.3%
8.0%
87.9%
2.9%
30.9%
18.9%
28.4%
91.7%
7.4%
33.6%
13.7%
21.4%
93.1%

506
17.6%
64.5%
21.9%
9.0%
76.1%
5.0%
45.6%
34.5%
28.3%
87.9%
12.9%
44.6%
27.2%
18.3%
86.7%

507
36.5%
45.4%
19.1%
11.3%
71.1%
23.1%
40.8%
25.5%
20.0%
83.9%
26.7%
40.9%
22.1%
15.3%
84.3%

508
23.4%
67.0%
21.6%
12.5%
72.9%
7.4%
61.3%
22.7%
15.7%
82.2%
14.5%
63.9%
22.3%
12.9%
84.2%

509
18.9%
63.4%
36.7%
8.6%
78.9%
9.9%
64.4%
63.5%
42.3%
88.1%
12.2%
53.0%
50.1%
27.5%
88.8%

510
11.0%
74.4%
16.5%
11.5%
81.6%
4.4%
44.1%
28.9%
32.5%
87.8%
9.5%
44.2%
21.2%
23.2%
88.0%

511
15.1%
65.4%
29.1%
11.4%
74.7%
5.0%
55.2%
35.4%
24.5%
86.6%
13.6%
47.7%
24.9%
16.5%
86.1%

512
55.4%
70.2%
29.3%
19.3%
85.0%
32.7%
48.2%
34.4%
30.2%
89.9%
38.9%
42.5%
24.0%
21.0%
91.0%

513
26.8%
69.0%
24.2%
22.6%
74.6%
9.1%
66.9%
32.3%
22.2%
84.7%
15.8%
67.9%
23.4%
14.8%
85.2%

514
19.3%
61.6%
39.3%
12.7%
74.3%
7.0%
51.2%
37.1%
20.4%
83.7%
15.4%
48.9%
30.0%
15.2%
86.2%

515
12.7%
62.8%
29.0%
32.2%
74.0%
4.7%
53.9%
24.8%
24.2%
85.2%
12.0%
44.2%
18.8%
17.9%
84.8%

516
15.9%
66.9%
34.3%
17.7%
76.0%
5.5%
62.9%
40.6%
28.1%
88.5%
12.1%
49.7%
26.2%
18.1%
86.6%

517
34.8%
50.9%
27.0%
27.9%
73.1%
34.2%
56.3%
37.1%
26.6%
86.7%
32.1%
49.4%
26.5%
19.6%
87.4%

518
24.1%
68.2%
23.7%
22.9%
74.3%
7.4%
67.3%
30.9%
19.4%
85.7%
15.4%
69.0%
24.8%
15.6%
86.9%

519
18.3%
66.8%
48.0%
20.1%
81.1%
8.0%
62.2%
52.8%
21.1%
87.4%
13.8%
48.9%
36.6%
13.7%
86.5%

520
14.4%
58.4%
28.0%
37.0%
72.7%
4.9%
54.0%
32.6%
29.3%
84.8%
12.4%
45.9%
23.1%
22.1%
83.4%

521
15.3%
62.1%
36.6%
23.3%
77.7%
9.0%
60.3%
39.1%
23.6%
88.0%
12.8%
46.5%
24.8%
16.8%
86.0%

522
40.1%
58.6%
26.0%
27.4%
79.8%
39.3%
55.4%
35.7%
30.5%
87.3%
33.0%
47.9%
27.2%
21.4%
87.7%

523
26.4%
63.4%
22.5%
21.8%
70.0%
18.6%
68.4%
32.2%
23.9%
85.3%
21.5%
70.6%
26.7%
17.5%
86.6%

524
19.0%
52.0%
33.9%
12.8%
76.0%
24.1%
59.1%
55.6%
29.2%
87.0%
16.7%
44.9%
37.0%
15.2%
84.0%

525
20.7%
60.8%
21.8%
32.1%
76.6%
6.4%
66.1%
37.1%
35.9%
88.3%
13.3%
54.5%
25.1%
25.7%
87.2%

526
21.3%
54.5%
22.9%
21.2%
77.6%
13.3%
66.8%
52.0%
34.9%
89.3%
14.1%
55.2%
36.9%
24.1%
88.9%

527
45.3%
57.5%
24.2%
19.0%
71.7%
33.2%
62.1%
40.3%
28.7%
87.4%
35.7%
55.5%
29.0%
19.9%
86.1%

528
33.6%
49.0%
27.7%
12.7%
73.3%
20.5%
62.5%
54.5%
31.4%
85.4%
20.1%
54.1%
39.1%
19.2%
84.4%

529
21.1%
56.9%
24.9%
32.2%
72.6%
12.2%
70.3%
34.7%
22.1%
86.9%
15.8%
63.9%
26.9%
20.3%
85.9%

530
27.1%
60.9%
22.2%
16.7%
73.3%
12.6%
69.5%
51.4%
23.9%
87.8%
17.1%
64.3%
41.0%
17.5%
87.2%

531
38.6%
60.8%
23.5%
17.7%
68.0%
13.8%
65.7%
37.7%
28.6%
84.8%
23.5%
67.4%
27.7%
17.1%
85.1%

532
31.5%
49.0%
24.7%
11.7%
69.0%
29.3%
51.0%
34.1%
18.0%
82.6%
26.6%
49.0%
29.3%
16.6%
82.9%

533
23.3%
57.7%
19.8%
21.1%
70.9%
9.4%
70.2%
41.4%
29.5%
86.7%
17.5%
58.2%
24.3%
20.2%
85.3%

534
31.4%
61.8%
24.5%
15.6%
72.6%
6.5%
74.5%
56.8%
25.2%
89.8%
19.6%
60.1%
33.7%
16.2%
87.8%

535
36.5%
55.2%
27.0%
14.9%
62.7%
36.2%
58.7%
43.6%
23.1%
81.1%
37.4%
57.6%
34.0%
17.1%
81.3%

536
38.4%
64.3%
25.9%
17.8%
71.2%
13.2%
68.8%
44.5%
33.7%
84.3%
26.9%
69.5%
27.8%
16.9%
85.0%

537
27.2%
62.1%
33.6%
13.0%
75.3%
19.5%
67.1%
46.1%
17.0%
87.2%
20.5%
53.3%
33.2%
13.3%
86.3%

538
26.0%
59.0%
23.3%
18.4%
67.9%
9.0%
61.5%
30.3%
24.0%
81.1%
20.3%
61.3%
25.4%
19.5%
82.7%

539
33.4%
70.6%
26.0%
14.7%
78.7%
15.2%
76.8%
64.5%
19.2%
89.3%
22.7%
74.3%
46.8%
14.2%
89.9%

540
47.6%
64.2%
33.7%
16.0%
71.4%
34.9%
65.7%
44.7%
22.4%
85.4%
39.6%
67.0%
35.1%
20.0%
84.5%

541
43.5%
64.0%
37.6%
24.3%
70.6%
7.2%
67.1%
42.3%
32.5%
84.7%
21.6%
69.0%
32.4%
20.1%
84.4%

542
29.1%
58.0%
37.1%
13.6%
66.6%
7.8%
60.0%
47.6%
27.1%
82.5%
20.2%
59.5%
38.9%
17.1%
81.6%

543
24.5%
60.9%
30.2%
23.2%
69.0%
7.8%
62.3%
34.3%
26.3%
84.2%
16.8%
63.1%
30.5%
24.2%
84.5%

544
29.2%
59.7%
32.0%
16.2%
67.7%
7.5%
60.1%
44.1%
25.6%
84.2%
21.6%
62.9%
37.6%
19.9%
86.6%

545
44.2%
61.7%
39.2%
15.1%
69.8%
29.1%
63.0%
48.0%
30.6%
85.2%
38.4%
65.3%
38.6%
20.3%
85.5%

546
36.8%
59.3%
43.6%
25.0%
65.9%
7.2%
63.1%
42.5%
33.2%
83.1%
23.8%
65.7%
37.7%
24.7%
82.8%

547
27.9%
58.2%
40.7%
16.1%
66.1%
8.2%
60.2%
45.2%
29.8%
82.8%
21.9%
63.3%
40.2%
20.5%
84.4%

548
20.9%
58.2%
28.4%
19.1%
66.4%
5.9%
63.8%
39.5%
31.2%
84.1%
16.0%
63.9%
29.7%
23.8%
82.9%

549
43.1%
66.6%
50.2%
26.2%
71.9%
16.5%
65.4%
47.7%
39.5%
84.2%
29.6%
68.5%
44.0%
27.7%
84.5%

550
27.7%
59.0%
44.3%
17.5%
66.4%
6.4%
60.4%
47.6%
32.0%
84.2%
24.7%
61.6%
41.0%
19.0%
82.3%

551
20.4%
57.5%
30.3%
20.1%
65.0%
7.3%
55.8%
38.7%
32.9%
79.6%
16.6%
58.9%
34.5%
27.1%
79.1%

552
27.7%
59.1%
40.4%
19.5%
66.8%
9.2%
63.1%
47.2%
34.0%
83.7%
22.9%
66.2%
44.6%
24.8%
83.5%

553
42.1%
58.7%
43.5%
29.4%
66.4%
21.2%
58.4%
44.0%
35.3%
84.0%
39.1%
63.6%
43.7%
29.1%
82.6%

554
42.7%
65.8%
49.2%
37.4%
71.0%
7.0%
68.5%
49.3%
46.7%
85.3%
27.6%
69.1%
43.3%
32.9%
84.3%

555
27.6%
57.7%
40.3%
17.3%
65.5%
6.1%
60.2%
46.2%
32.6%
84.9%
21.6%
62.6%
41.9%
22.2%
86.5%

556
23.2%
57.8%
38.8%
27.8%
64.7%
6.7%
62.2%
43.3%
39.0%
82.7%
20.2%
62.1%
39.2%
31.7%
81.8%

557
28.8%
62.4%
42.7%
24.3%
69.4%
6.2%
65.1%
47.6%
30.3%
85.7%
20.0%
68.9%
44.2%
24.3%
87.5%

558
42.2%
60.8%
43.8%
29.3%
68.3%
19.6%
54.4%
38.4%
35.7%
84.3%
34.5%
63.6%
38.7%
24.6%
84.0%

559
35.1%
61.3%
43.6%
27.4%
68.3%
6.3%
60.3%
47.3%
31.2%
83.8%
27.0%
60.6%
39.4%
21.3%
82.4%

560
29.9%
58.1%
39.2%
34.4%
66.4%
6.3%
63.1%
43.4%
41.6%
85.5%
26.5%
62.4%
33.7%
28.0%
85.1%

561
33.5%
64.8%
49.1%
33.7%
71.0%
7.7%
64.2%
45.1%
37.4%
83.6%
25.7%
66.6%
42.9%
29.4%
84.9%

562
49.6%
65.5%
49.5%
36.4%
71.8%
28.5%
56.9%
43.1%
48.1%
88.0%
42.3%
67.1%
45.2%
32.2%
85.3%

563
29.4%
60.9%
43.3%
28.8%
68.5%
11.5%
61.8%
50.5%
49.8%
87.3%
23.9%
64.0%
39.8%
27.4%
83.6%

564
28.6%
58.2%
40.9%
34.9%
65.1%
6.3%
70.5%
50.0%
45.4%
87.1%
27.9%
62.6%
35.0%
29.5%
82.0%

565
31.4%
63.3%
44.4%
30.2%
69.7%
7.1%
72.2%
55.8%
39.1%
88.7%
27.5%
68.0%
42.2%
25.1%
86.8%

566
50.0%
71.8%
59.3%
52.7%
76.7%
6.3%
71.9%
36.8%
31.6%
87.0%
30.7%
71.0%
30.3%
22.4%
84.6%

567
33.2%
59.6%
46.5%
28.6%
65.3%
7.0%
58.7%
48.2%
36.0%
83.9%
27.0%
58.8%
34.2%
18.5%
79.0%

568
29.0%
60.8%
41.1%
36.0%
68.5%
3.9%
49.7%
35.1%
35.4%
84.5%
21.8%
62.6%
30.8%
26.2%
83.9%

569
30.8%
60.9%
44.2%
28.5%
68.4%
7.1%
65.5%
48.4%
37.3%
87.9%
22.9%
65.1%
40.2%
24.7%
85.1%

570
40.6%
61.1%
43.2%
25.2%
67.3%
19.8%
55.9%
36.4%
35.0%
85.0%
34.1%
64.2%
38.3%
21.9%
84.7%

571
27.9%
60.9%
45.1%
37.2%
68.0%
9.9%
68.9%
34.9%
42.3%
85.3%
19.4%
69.3%
38.8%
33.3%
85.8%

572
25.1%
57.7%
42.4%
23.0%
65.0%
6.3%
57.1%
47.7%
38.5%
84.3%
17.0%
62.5%
37.6%
21.3%
83.5%

573
21.3%
57.9%
38.4%
32.2%
65.8%
6.6%
57.1%
39.1%
40.0%
88.4%
16.7%
63.1%
36.0%
30.4%
85.8%

574
35.6%
72.5%
49.3%
33.0%
77.5%
5.6%
82.2%
70.8%
48.5%
92.1%
20.2%
79.7%
57.3%
31.5%
91.1%

575
48.9%
65.7%
46.6%
28.0%
71.6%
25.9%
58.3%
41.5%
39.0%
88.0%
43.0%
68.8%
39.1%
25.0%
86.8%

576
35.4%
67.7%
53.4%
43.3%
73.7%
6.5%
50.9%
22.3%
17.3%
81.1%
14.9%
62.3%
25.8%
17.0%
84.1%

577
21.6%
57.9%
42.6%
22.1%
65.4%
7.0%
57.5%
47.3%
32.9%
88.2%
15.7%
63.3%
38.3%
20.2%
84.3%

578
21.2%
62.6%
42.3%
36.1%
69.2%
6.4%
51.7%
36.0%
43.2%
85.2%
14.8%
62.1%
32.4%
29.9%
83.8%

579
39.3%
60.2%
42.3%
24.1%
66.7%
16.2%
43.0%
28.2%
24.8%
84.6%
31.2%
64.1%
36.4%
20.3%
84.8%

580
30.9%
62.5%
47.9%
38.7%
69.0%
6.3%
66.2%
31.2%
29.3%
83.5%
16.8%
66.7%
36.5%
25.9%
83.9%

581
20.1%
58.0%
44.3%
23.4%
65.2%
7.8%
47.4%
39.6%
24.7%
83.2%
16.5%
61.2%
38.3%
17.2%
80.2%

582
20.7%
61.3%
39.8%
32.0%
68.1%
4.6%
61.4%
40.5%
38.7%
86.7%
15.1%
66.4%
34.5%
29.1%
84.2%

583
22.0%
59.6%
41.7%
22.8%
65.9%
5.9%
55.7%
36.2%
26.0%
82.5%
16.5%
64.6%
36.2%
21.9%
84.7%

584
43.3%
62.0%
44.2%
27.8%
68.8%
21.1%
53.6%
40.5%
34.9%
87.3%
36.3%
65.0%
42.0%
25.8%
88.2%

585
32.6%
63.8%
48.8%
40.4%
70.0%
6.7%
72.4%
35.8%
31.3%
87.6%
17.1%
72.2%
33.4%
23.2%
85.5%

586
21.9%
60.1%
46.1%
25.8%
66.5%
5.9%
47.6%
39.5%
26.4%
83.9%
15.3%
63.5%
40.0%
16.5%
83.7%

587
18.5%
61.5%
40.8%
34.0%
67.0%
4.3%
45.7%
32.3%
38.2%
84.3%
12.7%
62.1%
31.0%
29.9%
86.0%

588
19.9%
63.0%
47.2%
28.6%
69.9%
4.8%
69.8%
53.7%
41.0%
88.6%
14.4%
71.0%
48.2%
29.2%
86.9%

589
41.3%
59.6%
43.9%
29.2%
66.5%
16.6%
45.0%
32.6%
37.8%
89.7%
38.0%
64.0%
40.6%
29.4%
89.2%

590
31.8%
62.1%
48.1%
39.0%
67.6%
6.5%
72.5%
35.9%
33.3%
86.5%
17.3%
73.3%
33.7%
25.6%
85.7%

591
19.2%
54.9%
35.5%
28.8%
61.4%
4.5%
54.7%
35.6%
38.0%
83.2%
14.3%
58.9%
30.4%
30.0%
82.1%

592
22.6%
63.3%
45.6%
28.2%
69.4%
4.7%
61.8%
44.8%
35.3%
88.3%
13.7%
64.4%
40.3%
27.6%
87.5%

593
64.2%
77.0%
57.8%
32.5%
81.2%
26.1%
59.0%
46.8%
38.6%
94.0%
58.6%
63.7%
42.9%
32.0%
93.8%

594
42.4%
73.8%
57.3%
46.0%
78.2%
6.5%
80.4%
27.7%
24.0%
91.0%
17.4%
83.5%
25.6%
19.2%
91.8%

595
22.7%
60.6%
42.8%
25.5%
68.4%
10.1%
64.6%
47.4%
44.1%
88.1%
20.1%
65.1%
44.3%
32.0%
89.2%

596
23.8%
59.8%
34.5%
28.8%
67.8%
5.6%
59.7%
41.1%
42.9%
87.6%
17.0%
60.1%
35.7%
39.6%
87.8%

597
26.9%
63.7%
40.2%
23.5%
70.3%
5.7%
70.0%
53.9%
40.7%
90.2%
16.7%
63.9%
40.1%
31.1%
90

598
49.0%
63.0%
37.6%
24.0%
69.4%
16.5%
50.1%
36.6%
33.8%
88.5%
45.5%
53.7%
34.4%
27.4%
86.3%

599
33.8%
63.2%
45.4%
37.0%
69.2%
10.4%
78.3%
41.1%
57.5%
89.5%
19.8%
79.5%
41.1%
50.7%
89.5%

600
25.9%
59.3%
42.9%
20.5%
66.7%
9.9%
64.9%
52.9%
46.6%
86.6%
19.4%
65.2%
48.0%
35.0%
86.2%

601
23.7%
65.5%
35.8%
32.2%
71.2%
4.8%
58.5%
54.4%
55.3%
90.6%
15.7%
62.4%
46.6%
49.8%
89.6%

602
29.7%
64.2%
38.5%
24.2%
71.1%
6.8%
72.3%
57.7%
43.2%
89.1%
18.1%
68.0%
46.5%
33.2%
89.9%

603
46.2%
61.7%
38.8%
22.7%
68.2%
23.6%
51.9%
50.4%
51.2%
89.6%
43.2%
67.3%
48.8%
39.4%
88.9%

604
47.1%
71.6%
44.2%
34.6%
76.2%
6.7%
68.6%
28.6%
23.1%
85.6%
21.3%
75.7%
26.4%
17.9%
88.8%

605
29.9%
68.9%
36.4%
34.5%
74.2%
3.5%
61.9%
44.7%
51.1%
92.7%
18.9%
64.4%
32.9%
41.2%
92.1%

606
40.5%
79.2%
43.0%
20.6%
83.6%
5.4%
78.3%
55.5%
37.0%
93.6%
25.6%
76.4%
44.9%
30.7%
93.6%

607
49.7%
65.8%
37.8%
20.5%
72.3%
18.2%
58.4%
33.1%
30.8%
89.0%
45.7%
63.9%
35.9%
24.2%
87.7%

608
43.9%
65.1%
36.2%
30.5%
70.3%
6.5%
78.8%
55.8%
49.6%
88.7%
29.2%
75.7%
38.8%
29.6%
87.9%

609
30.7%
61.8%
42.2%
16.1%
69.2%
8.3%
68.0%
53.1%
40.3%
89.4%
23.7%
62.3%
43.5%
26.3%
86.0%

610
29.5%
66.5%
34.1%
31.6%
73.5%
5.8%
67.3%
48.4%
48.5%
90.3%
23.0%
66.2%
38.5%
37.1%
87.9%

611
33.6%
65.7%
35.7%
20.6%
72.4%
4.8%
75.1%
58.2%
37.0%
91.5%
22.4%
69.7%
44.6%
27.2%
90.5%

612
48.8%
64.4%
36.8%
20.8%
70.9%
22.5%
51.8%
35.6%
25.3%
85.1%
47.2%
65.1%
43.2%
25.6%
86.4%

613
46.1%
66.3%
41.9%
37.1%
72.0%
8.6%
67.6%
36.2%
36.4%
85.0%
22.8%
73.3%
40.1%
37.0%
85.9%

614
32.3%
61.3%
41.2%
16.8%
67.9%
6.6%
59.3%
47.0%
30.7%
87.4%
22.0%
58.7%
42.1%
21.7%
87.9%

615
25.3%
61.3%
32.9%
28.6%
68.4%
6.2%
63.1%
43.2%
41.1%
86.7%
25.3%
65.2%
38.3%
34.7%
87.7%

616
31.2%
62.1%
33.4%
20.1%
68.8%
5.6%
71.8%
55.8%
39.5%
88.4%
25.5%
68.5%
45.8%
29.2%
88.0%

617
43.1%
60.3%
31.5%
21.1%
69.7%
31.2%
66.7%
47.1%
30.7%
88.2%
44.8%
69.0%
40.7%
25.3%
88.5%

618
34.3%
63.5%
34.5%
28.3%
70.5%
6.8%
72.2%
31.6%
29.8%
87.2%
23.9%
72.6%
26.4%
20.3%
88.4%

619
24.9%
58.0%
34.5%
16.7%
67.6%
10.3%
66.4%
52.5%
32.0%
88.1%
21.6%
60.6%
39.9%
19.1%
85.8%

620
21.2%
58.1%
28.7%
29.3%
66.7%
6.8%
69.8%
47.4%
37.7%
87.8%
20.6%
67.6%
41.6%
33.7%
85.8%

621
26.8%
62.7%
33.1%
20.9%
71.3%
5.4%
73.0%
55.0%
31.1%
90.3%
23.0%
67.9%
39.9%
21.0%
89.4%

622
46.4%
66.4%
22.7%
9.9%
76.6%
25.5%
38.4%
27.2%
30.9%
84.9%
32.9%
43.6%
25.7%
21.3%
87.3%

623
21.8%
72.0%
21.1%
9.9%
78.1%
6.5%
54.9%
18.7%
12.6%
85.4%
14.5%
60.4%
20.4%
13.3%
87.0%

624
16.0%
67.3%
42.8%
6.9%
79.3%
4.1%
26.9%
21.1%
13.6%
85.1%
12.6%
34.4%
22.2%
12.2%
85.8%

625
9.8%
83.6%
9.9%
5.3%
88.5%
3.3%
43.8%
17.5%
27.0%
92.5%
8.0%
48.3%
14.7%
19.3%
93.0%

626
15.8%
63.7%
24.4%
8.8%
78.1%
4.2%
43.8%
25.7%
18.5%
87.1%
11.9%
42.6%
22.5%
14.2%
86.2%

627
41.5%
54.0%
21.6%
12.4%
72.2%
19.8%
48.1%
33.1%
23.1%
85.3%
28.4%
47.7%
27.7%
17.3%
86.6%

628
21.0%
68.4%
25.6%
14.5%
76.1%
5.7%
55.7%
19.1%
14.9%
83.6%
13.7%
56.1%
20.2%
13.9%
86.6%

629
14.7%
71.8%
35.8%
8.2%
81.6%
4.7%
27.3%
19.7%
12.3%
86.4%
11.4%
34.1%
18.8%
11.3%
88.0%

630
14.4%
65.7%
19.6%
13.4%
73.9%
5.8%
36.1%
18.8%
21.3%
83.4%
13.5%
45.9%
22.2%
18.5%
85.5%

631
14.4%
64.4%
26.0%
10.3%
74.8%
6.2%
39.6%
21.5%
15.4%
85.0%
10.8%
39.1%
19.3%
13.0%
85.0%

632
35.9%
60.9%
30.3%
25.7%
72.5%
34.4%
58.2%
51.0%
22.6%
86.2%
37.7%
55.4%
42.2%
18.7%
85.5%

633
25.2%
66.8%
29.7%
21.0%
72.6%
7.0%
66.1%
31.7%
20.5%
84.3%
15.7%
69.3%
25.6%
15.6%
85.2%

634
15.0%
65.7%
49.8%
19.3%
75.8%
18.0%
64.5%
54.3%
21.5%
86.6%
16.4%
59.6%
45.9%
16.8%
88.0%

635
8.5%
79.7%
21.7%
19.9%
84.9%
4.1%
32.9%
17.4%
34.6%
89.4%
10.0%
39.7%
16.1%
19.6%
88.2%

636
25.9%
70.5%
27.1%
17.1%
82.4%
6.0%
51.6%
26.1%
18.7%
87.3%
12.5%
50.9%
23.5%
15.4%
89.8%

637
41.3%
48.0%
23.1%
18.6%
71.2%
22.4%
47.5%
27.0%
20.0%
86.3%
34.0%
46.9%
22.6%
16.3%
86.6%

638
27.4%
65.8%
26.6%
27.0%
73.8%
16.4%
67.7%
36.9%
25.4%
87.4%
20.4%
70.5%
31.1%
19.3%
88.7%

639
20.3%
67.2%
48.2%
18.7%
78.7%
8.4%
38.8%
35.1%
23.5%
88.2%
15.2%
42.9%
28.0%
15.1%
88.3%

640
22.3%
58.4%
21.6%
30.7%
77.7%
6.0%
56.8%
22.8%
38.1%
91.7%
15.5%
48.0%
17.5%
27.5%
91.0%

641
20.6%
65.3%
26.8%
24.1%
84.2%
10.9%
69.3%
45.9%
24.4%
90.7%
14.1%
56.1%
30.4%
17.9%
90.2%

642
54.1%
64.3%
22.2%
21.9%
79.4%
29.3%
51.5%
27.7%
22.0%
89.7%
48.9%
49.5%
21.8%
14.9%
90.1%

643
30.0%
69.2%
22.2%
22.2%
75.3%
10.6%
69.6%
29.6%
19.7%
87.9%
19.0%
73.9%
25.7%
15.1%
87.8%

644
26.6%
65.3%
33.3%
10.2%
83.5%
8.5%
54.6%
38.5%
16.7%
91.0%
17.2%
45.9%
27.0%
12.3%
91.0%

645
16.0%
54.6%
22.0%
34.6%
76.2%
5.8%
40.7%
21.4%
32.9%
86.8%
15.2%
42.0%
19.5%
22.6%
88.4%

646
23.9%
65.2%
20.2%
19.3%
83.8%
10.1%
78.2%
51.7%
17.1%
91.7%
14.9%
65.7%
29.9%
13.0%
91.5%

647
45.2%
61.1%
27.6%
24.4%
72.5%
38.9%
63.7%
39.8%
24.7%
88.5%
44.9%
64.4%
33.4%
20.1%
88.8%

648
33.7%
67.1%
21.8%
19.0%
73.9%
32.7%
73.4%
20.6%
18.3%
87.6%
32.4%
75.6%
21.5%
14.4%
89.6%

649
27.5%
52.5%
28.3%
12.9%
72.0%
11.5%
60.4%
47.0%
22.8%
86.3%
19.9%
53.2%
34.9%
16.5%
86.3%

650
23.0%
58.4%
21.6%
27.0%
73.2%
10.1%
67.8%
31.7%
27.0%
86.1%
16.6%
61.4%
24.8%
21.5%
86.2%

651
24.3%
57.9%
24.3%
18.5%
72.9%
6.4%
63.0%
34.7%
24.5%
88.5%
16.8%
55.6%
26.5%
17.6%
87.9%

652
44.5%
67.1%
24.6%
19.4%
73.3%
7.8%
69.8%
33.3%
23.0%
86.8%
25.2%
74.0%
25.0%
16.6%
88.7%

653
32.0%
53.3%
26.8%
13.0%
72.3%
20.2%
60.4%
45.7%
23.9%
87.9%
27.1%
54.4%
31.9%
16.3%
88.3%

654
22.2%
54.8%
19.8%
19.4%
69.8%
5.5%
61.1%
30.9%
31.8%
87.8%
19.2%
56.7%
22.1%
19.8%
85.7%

655
30.6%
57.9%
25.0%
16.4%
69.9%
11.0%
66.6%
41.1%
22.6%
86.2%
21.6%
60.1%
27.9%
16.5%
84.9%

656
45.1%
61.4%
27.9%
18.6%
68.4%
22.6%
60.4%
35.2%
22.1%
83.8%
39.1%
64.1%
33.5%
19.9%
85.7%

657
38.6%
60.5%
31.6%
21.2%
67.5%
9.8%
61.8%
28.4%
21.7%
83.0%
25.0%
66.5%
27.4%
17.4%
83.9%

658
29.4%
63.9%
24.5%
22.4%
71.3%
6.3%
64.3%
33.4%
22.1%
83.9%
22.6%
65.5%
27.2%
19.2%
85.5%

659
29.9%
60.3%
29.7%
16.5%
68.1%
13.3%
64.8%
47.7%
22.7%
85.2%
22.5%
66.2%
37.3%
19.3%
86.0%

660
40.9%
57.9%
28.0%
16.8%
67.1%
23.1%
59.3%
39.6%
28.0%
85.0%
36.2%
58.3%
29.0%
20.3%
83.1%

661
38.5%
65.1%
32.8%
21.0%
71.1%
14.3%
64.9%
30.9%
28.5%
83.9%
26.5%
67.7%
28.3%
19.8%
84.5%

662
35.4%
60.0%
33.3%
13.8%
70.7%
8.2%
60.4%
44.0%
22.9%
84.6%
25.5%
59.2%
34.7%
16.5%
85.2%

663
27.5%
61.7%
24.8%
20.7%
69.9%
6.6%
66.0%
32.8%
22.5%
84.8%
23.3%
64.5%
27.2%
20.9%
84.5%

664
28.0%
58.5%
32.8%
15.4%
66.4%
8.0%
63.2%
46.0%
24.7%
84.5%
23.0%
64.8%
35.5%
19.7%
84.6%

665
37.8%
57.4%
33.9%
18.3%
65.4%
23.9%
57.6%
36.6%
30.8%
85.8%
35.7%
59.2%
32.1%
20.6%
84.4%

666
33.8%
59.3%
40.8%
24.9%
65.5%
8.1%
63.3%
40.5%
33.7%
84.2%
29.3%
67.5%
34.4%
22.1%
85.0%

667
27.1%
57.7%
35.3%
14.7%
66.3%
9.7%
60.6%
45.6%
35.6%
84.2%
22.7%
60.9%
37.1%
20.9%
83.9%

668
22.3%
58.1%
30.6%
20.4%
65.5%
7.2%
62.8%
38.8%
31.0%
83.6%
22.2%
63.8%
30.6%
24.0%
83.7%

669
28.5%
57.3%
35.8%
14.2%
65.2%
5.8%
63.0%
44.0%
31.5%
83.6%
21.9%
61.9%
33.8%
20.9%
83.1%

670
47.6%
65.2%
48.3%
20.1%
71.2%
31.8%
62.5%
45.8%
37.0%
85.4%
43.2%
70.2%
48.2%
27.6%
87.0%

671
29.5%
66.2%
43.9%
13.1%
74.9%
18.2%
61.7%
49.6%
30.5%
83.2%
27.6%
65.4%
47.8%
18.9%
86.1%

672
23.3%
59.7%
35.5%
25.4%
67.5%
5.7%
59.8%
38.2%
32.8%
83.0%
20.0%
65.7%
36.4%
28.8%
83.1%

673
29.2%
61.6%
42.9%
18.9%
68.3%
6.0%
62.0%
43.5%
31.0%
85.4%
24.3%
67.0%
38.8%
21.9%
85.6%

674
42.4%
60.8%
42.2%
17.5%
69.4%
21.4%
53.2%
33.5%
33.9%
84.7%
34.6%
63.4%
37.1%
23.8%
84.7%

675
37.0%
62.6%
45.9%
34.7%
69.5%
9.8%
67.3%
50.0%
45.8%
85.9%
27.8%
68.3%
47.0%
33.3%
85.4%

676
25.6%
56.6%
37.4%
15.9%
63.7%
8.8%
56.4%
40.1%
31.3%
83.1%
25.2%
62.6%
36.9%
20.4%
84.1%

677
23.1%
60.4%
36.4%
25.9%
67.3%
7.9%
64.7%
40.4%
30.1%
85.0%
23.0%
66.6%
38.8%
27.3%
84.0%

678
30.5%
62.5%
44.3%
23.8%
70.3%
6.1%
63.8%
48.3%
28.6%
84.5%
25.0%
66.2%
43.6%
23.2%
85.1%

679
51.0%
68.5%
52.3%
29.8%
74.1%
18.1%
56.5%
35.0%
38.8%
87.0%
41.2%
64.4%
37.8%
26.8%
85.3%

680
45.4%
68.9%
54.1%
46.2%
75.0%
6.0%
67.1%
30.2%
31.1%
85.9%
36.2%
70.1%
37.5%
29.6%
87.3%

681
21.5%
62.8%
40.2%
31.3%
69.8%
6.9%
56.5%
35.0%
39.7%
85.2%
21.3%
65.1%
34.8%
32.4%
85.3%

682
30.8%
60.7%
44.3%
29.7%
67.5%
5.7%
62.6%
42.5%
39.1%
85.3%
30.2%
66.7%
40.7%
27.1%
85.6%

683
42.3%
59.9%
45.5%
30.5%
65.9%
18.6%
56.7%
34.3%
35.9%
86.0%
40.2%
63.9%
37.3%
24.8%
83.7%

684
40.6%
63.9%
50.2%
42.4%
69.7%
6.4%
71.2%
44.5%
37.4%
87.8%
30.2%
68.2%
35.9%
24.6%
84.6%

685
35.5%
64.3%
48.8%
31.6%
70.6%
6.5%
52.0%
37.9%
25.0%
86.0%
31.0%
65.9%
37.7%
19.1%
86.6%

686
28.3%
58.4%
39.8%
33.3%
66.1%
6.5%
56.1%
36.8%
40.7%
85.5%
28.8%
65.1%
32.7%
29.0%
83.4%

687
40.5%
66.7%
53.1%
37.5%
73.0%
5.5%
66.3%
45.0%
35.9%
87.3%
34.8%
68.9%
37.1%
23.7%
88.0%

688
41.9%
61.8%
43.9%
29.5%
68.9%
20.4%
55.9%
38.9%
31.5%
85.9%
38.6%
66.1%
40.9%
25.0%
85.0%

689
35.9%
62.3%
45.1%
36.9%
68.0%
7.7%
64.1%
30.8%
31.3%
85.5%
25.8%
66.6%
34.4%
26.9%
83.8%

690
30.1%
61.5%
44.5%
29.3%
69.2%
8.6%
49.9%
39.0%
39.6%
84.8%
25.7%
62.1%
37.4%
24.5%
82.7%

691
26.3%
57.4%
37.5%
31.3%
65.2%
5.2%
45.6%
30.0%
31.3%
83.5%
21.2%
61.1%
29.1%
21.7%
81.8%

692
30.3%
60.6%
42.0%
27.6%
67.9%
5.5%
58.4%
37.4%
40.0%
85.8%
25.5%
64.7%
34.3%
23.6%
83.8%

693
39.7%
57.7%
41.6%
26.7%
64.8%
17.9%
53.6%
37.8%
35.3%
84.9%
34.2%
64.6%
39.7%
24.5%
84.2%

694
40.5%
70.7%
57.0%
51.7%
75.7%
8.6%
77.8%
31.7%
37.0%
89.9%
22.8%
76.9%
39.8%
35.1%
89.0%

695
35.5%
66.6%
50.9%
27.2%
72.4%
4.4%
48.4%
34.9%
29.0%
88.7%
24.9%
64.5%
32.0%
17.7%
84.3%

696
24.7%
60.1%
39.1%
32.9%
67.8%
5.1%
46.1%
30.4%
36.3%
84.4%
17.6%
64.9%
29.2%
24.4%
85.1%

697
21.0%
62.1%
43.5%
28.0%
68.8%
7.4%
67.5%
41.2%
31.6%
86.6%
15.1%
66.7%
41.3%
29.9%
83.6%

698
39.4%
60.8%
44.7%
27.1%
67.4%
11.8%
40.3%
23.4%
31.2%
86.8%
30.0%
66.0%
39.8%
21.8%
85.1%

699
32.8%
65.0%
50.5%
41.6%
70.9%
8.6%
70.6%
37.3%
34.0%
87.6%
18.6%
70.8%
40.6%
31.7%
85.9%

700
24.0%
59.0%
45.6%
22.7%
66.3%
5.3%
45.1%
33.7%
21.2%
84.6%
16.4%
64.2%
38.9%
16.8%
84.0%

701
25.0%
67.9%
42.2%
38.8%
74.1%
4.5%
69.1%
44.6%
40.9%
89.0%
15.3%
72.4%
35.4%
32.3%
89.7%

702
22.6%
65.7%
46.5%
27.8%
71.9%
7.6%
64.0%
41.0%
41.0%
87.9%
16.4%
70.7%
44.5%
30.2%
88.6%

703
38.3%
57.1%
42.4%
24.9%
63.9%
12.7%
50.2%
34.4%
29.1%
85.8%
30.2%
63.6%
37.2%
21.0%
84.1%

704
28.3%
65.1%
51.4%
43.2%
72.7%
10.4%
75.7%
36.8%
45.7%
90.8%
19.6%
69.6%
41.6%
36.3%
88.4%

705
19.1%
55.9%
40.7%
23.9%
64.4%
9.6%
59.8%
50.4%
33.6%
84.8%
16.8%
62.0%
40.9%
21.8%
82.6%

706
19.4%
59.9%
39.7%
30.0%
67.6%
6.7%
44.9%
29.1%
37.5%
86.4%
15.4%
64.7%
31.7%
24.6%
85.0%

707
21.9%
62.1%
44.7%
25.5%
69.5%
5.5%
62.8%
38.9%
34.4%
87.6%
16.4%
68.3%
37.7%
21.2%
86.9%

708
40.2%
59.1%
41.5%
25.0%
65.8%
15.7%
49.4%
29.0%
27.8%
86.2%
37.5%
64.9%
34.7%
20.8%
85.3%

709
29.3%
61.0%
45.1%
36.7%
67.7%
8.7%
63.2%
27.7%
26.2%
84.3%
17.8%
68.7%
30.7%
23.7%
86.3%

710
23.1%
62.3%
46.9%
26.1%
69.1%
5.3%
49.4%
38.7%
24.5%
86.8%
16.9%
66.5%
42.9%
18.9%
87.0%

711
18.4%
55.4%
35.7%
29.9%
62.2%
4.9%
42.9%
24.4%
28.3%
82.4%
13.5%
59.5%
27.5%
24.5%
81.4%

712
23.4%
64.2%
47.4%
28.3%
71.0%
5.5%
56.2%
33.6%
24.4%
87.7%
15.2%
67.8%
38.5%
23.5%
88.7%

713
40.1%
62.0%
44.9%
29.8%
69.9%
14.9%
42.1%
25.0%
33.9%
86.6%
34.1%
66.0%
40.1%
28.2%
87.8%

714
34.2%
66.7%
51.9%
43.1%
72.9%
13.9%
76.3%
47.4%
34.0%
90.1%
22.0%
76.6%
41.8%
30.5%
90.3%

715
23.0%
62.4%
47.9%
26.9%
69.3%
4.8%
51.4%
39.2%
22.4%
87.6%
15.9%
66.5%
43.2%
19.0%
87.8%

716
22.7%
61.0%
42.6%
24.9%
68.6%
6.6%
64.8%
42.0%
43.7%
90.9%
15.2%
70.6%
42.0%
31.9%
90.4%

717
44.4%
62.2%
44.9%
27.7%
69.4%
11.0%
39.8%
22.2%
29.7%
87.9%
40.1%
55.7%
28.3%
24.2%
89.7%

718
41.9%
66.9%
48.8%
39.7%
73.1%
6.5%
65.9%
30.1%
22.0%
85.6%
22.1%
73.7%
27.7%
18.3%
88.2%

719
24.7%
63.0%
47.7%
23.5%
69.7%
5.5%
54.8%
48.4%
29.4%
89.8%
20.0%
58.0%
42.8%
19.6%
89.3%

720
21.6%
59.5%
36.4%
30.0%
65.8%
5.6%
50.7%
33.1%
42.3%
86.3%
16.2%
57.0%
31.8%
38.7%
87.7%

721
24.4%
61.5%
42.3%
23.1%
67.7%
3.5%
54.4%
32.3%
40.7%
90.1%
16.9%
56.4%
27.6%
26.3%
90.6%

722
44.8%
62.0%
42.3%
26.2%
69.2%
21.4%
59.2%
42.8%
34.6%
90.4%
47.9%
64.2%
39.9%
28.3%
90.0%

723
34.6%
62.9%
41.4%
31.4%
69.8%
9.3%
66.1%
21.8%
26.7%
85.9%
17.4%
72.5%
25.0%
23.3%
88.0%

724
29.6%
66.8%
45.2%
20.5%
74.0%
5.5%
40.0%
37.2%
39.6%
91.8%
21.5%
54.2%
34.6%
24.0%
91.6%

725
21.7%
62.5%
35.2%
29.6%
69.7%
5.6%
62.9%
44.9%
45.4%
88.4%
19.4%
66.2%
44.4%
44.7%
87.8%

726
26.1%
61.0%
37.8%
23.7%
68.4%
4.4%
53.4%
32.2%
27.1%
86.2%
20.6%
55.9%
30.1%
22.1%
87.8%

727
50.9%
64.2%
38.8%
21.1%
69.8%
30.1%
46.7%
34.9%
47.8%
91.3%
57.6%
65.2%
37.5%
34.2%
90.0%

728
46.7%
69.1%
42.3%
33.0%
74.2%
8.0%
78.4%
40.2%
33.6%
89.9%
28.0%
80.8%
30.8%
21.8%
90.6%

729
29.1%
59.7%
40.9%
18.6%
67.4%
5.6%
45.4%
37.6%
32.4%
87.1%
19.9%
50.4%
32.9%
23.4%
85.1%

730
26.5%
63.2%
33.3%
29.9%
69.0%
4.4%
58.4%
37.0%
40.6%
90.3%
19.3%
63.8%
30.2%
33.1%
90.8%

731
35.7%
69.1%
40.7%
21.3%
74.5%
10.7%
77.5%
68.2%
30.3%
92.1%
27.7%
74.8%
59.2%
26.3%
90.5%

732
43.5%
59.7%
35.4%
20.3%
66.1%
21.6%
55.2%
42.5%
33.8%
86.8%
46.0%
62.9%
40.9%
26.8%
86.7%

733
41.2%
62.8%
37.3%
30.1%
69.2%
9.6%
79.6%
46.1%
39.2%
90.6%
26.1%
77.6%
36.2%
26.1%
88.8%

734
38.6%
65.5%
44.3%
17.6%
72.5%
10.9%
71.8%
61.3%
38.7%
92.0%
30.9%
67.9%
47.0%
22.3%
90.5%

735
25.7%
62.7%
34.8%
30.0%
68.7%
4.7%
45.4%
30.2%
43.5%
87.4%
17.1%
57.1%
26.7%
34.8%
88.0%

736
34.0%
63.9%
35.8%
20.6%
69.7%
5.7%
69.1%
42.3%
26.4%
87.8%
29.5%
67.2%
35.5%
20.4%
85.8%

737
51.1%
65.8%
38.9%
23.7%
72.9%
43.2%
70.6%
61.4%
36.8%
89.9%
54.9%
75.4%
59.4%
30.0%
89.6%

738
42.5%
65.7%
36.0%
31.3%
72.3%
6.4%
71.6%
27.0%
29.3%
87.3%
28.9%
76.8%
27.2%
22.5%
89.2%

739
33.1%
66.0%
43.0%
15.8%
72.2%
4.6%
54.5%
43.5%
22.5%
91.3%
23.8%
55.3%
36.5%
15.2%
91.8%

740
27.3%
64.0%
35.1%
31.4%
71.4%
8.4%
62.5%
44.0%
47.6%
88.5%
22.4%
68.2%
39.7%
41.2%
89.0%

741
36.3%
65.6%
36.4%
21.7%
72.5%
4.5%
68.4%
49.1%
30.2%
89.8%
27.0%
69.5%
45.8%
23.6%
89.4%

742
42.5%
61.2%
30.2%
20.7%
71.6%
23.2%
56.6%
27.8%
21.6%
86.9%
34.0%
64.7%
31.1%
24.6%
89.0%

743
33.3%
64.6%
34.4%
29.5%
71.7%
6.5%
73.9%
39.8%
28.9%
88.5%
27.4%
75.2%
32.2%
21.6%
89.5%

744
25.9%
59.7%
36.8%
18.0%
70.1%
6.4%
49.5%
37.7%
24.4%
87.4%
18.5%
60.9%
37.0%
19.7%
87.0%

745
22.5%
58.6%
30.7%
28.3%
66.6%
4.5%
64.1%
30.2%
28.1%
86.5%
18.3%
67.7%
28.5%
24.8%
85.8%

746
22.4%
61.3%
31.3%
20.5%
69.7%
11.9%
67.4%
30.9%
20.7%
88.2%
18.4%
69.0%
33.4%
21.7%
88.7%

747
24.7%
76.5%
20.8%
9.0%
81.4%
5.9%
58.5%
18.3%
12.9%
88.1%
14.0%
72.4%
19.5%
11.3%
90.6%

748
12.1%
76.3%
23.6%
12.4%
82.4%
6.1%
47.6%
46.6%
48.4%
87.1%
12.9%
53.2%
40.1%
43.7%
88.9%

749
19.6%
72.1%
23.5%
8.1%
80.9%
4.9%
33.3%
17.5%
16.8%
86.9%
11.6%
40.4%
17.9%
12.9%
90.0%

750
49.4%
73.1%
26.1%
9.3%
85.0%
18.2%
42.2%
25.6%
15.4%
90.2%
28.9%
44.2%
21.5%
13.0%
91.1%

751
25.7%
68.8%
26.1%
14.5%
74.3%
7.6%
64.6%
29.5%
17.6%
86.2%
13.9%
69.6%
26.1%
15.3%
87.9%

752
12.4%
70.7%
22.0%
12.8%
78.0%
5.4%
45.8%
31.6%
32.6%
86.0%
12.4%
49.8%
22.2%
20.8%
87.0%

753
19.2%
61.9%
22.7%
11.7%
76.2%
5.5%
48.1%
28.0%
19.8%
87.1%
12.5%
48.9%
24.5%
15.3%
88.3%

754
46.3%
61.2%
33.7%
21.2%
73.0%
15.0%
39.2%
22.8%
17.0%
82.5%
30.2%
47.3%
25.0%
15.5%
85.3%

755
22.4%
66.5%
33.9%
24.8%
72.4%
6.5%
65.1%
20.0%
15.2%
83.3%
16.2%
68.3%
23.0%
15.0%
86.5%

756
20.0%
60.9%
42.0%
15.9%
74.1%
9.5%
54.5%
36.6%
18.8%
83.3%
17.4%
50.2%
30.9%
16.9%
85.3%

757
16.1%
82.1%
33.0%
33.6%
87.0%
16.0%
65.6%
49.7%
34.0%
92.0%
17.2%
67.4%
39.9%
27.8%
92.9%

758
14.3%
69.6%
31.8%
13.3%
77.0%
5.9%
49.0%
29.0%
18.3%
85.4%
13.3%
47.3%
23.2%
14.8%
85.3%

759
47.6%
64.1%
26.1%
28.2%
83.0%
23.7%
48.1%
23.6%
17.0%
91.0%
25.9%
47.4%
20.5%
15.2%
90.9%

760
20.5%
68.6%
22.1%
28.5%
77.8%
14.9%
70.5%
21.4%
13.3%
87.4%
17.2%
71.0%
21.1%
14.5%
88.7%

761
17.0%
55.4%
41.1%
18.1%
71.4%
6.7%
39.7%
27.3%
15.3%
81.6%
15.3%
46.9%
26.3%
14.0%
82.1%

762
14.9%
50.8%
24.7%
35.5%
76.3%
8.2%
62.2%
17.5%
17.0%
89.0%
14.5%
47.7%
18.9%
17.1%
88.6%

763
20.7%
67.2%
27.0%
25.2%
83.2%
7.0%
66.8%
42.1%
25.3%
90.6%
13.9%
58.8%
29.4%
18.5%
90.6%

764
49.0%
56.7%
21.1%
19.3%
78.5%
40.8%
72.8%
41.7%
15.3%
91.3%
49.9%
59.1%
26.0%
13.8%
91.4%

765
38.0%
68.2%
20.0%
19.7%
75.5%
30.8%
72.4%
17.2%
13.3%
86.8%
27.0%
74.9%
20.0%
14.8%
88.8%

766
23.3%
52.1%
29.1%
13.7%
70.6%
6.9%
45.4%
26.8%
16.5%
84.1%
17.8%
48.9%
25.1%
15.1%
84.2%

767
25.2%
53.3%
21.7%
28.3%
72.2%
5.4%
71.0%
31.6%
23.7%
89.3%
22.1%
60.6%
25.1%
19.3%
86.7%

768
20.8%
61.8%
27.1%
24.5%
77.3%
20.3%
70.6%
52.9%
17.4%
89.1%
18.1%
66.8%
40.9%
16.9%
90.1%

769
52.0%
65.4%
25.1%
18.9%
75.0%
34.5%
61.6%
33.7%
18.4%
88.1%
41.6%
61.7%
29.0%
16.3%
87.9%

770
35.0%
63.0%
23.9%
20.2%
70.9%
10.7%
69.4%
28.0%
16.9%
85.6%
23.3%
70.4%
24.8%
16.9%
87.5%

771
31.7%
55.5%
27.3%
13.4%
72.7%
8.7%
50.6%
35.0%
17.9%
84.1%
24.6%
55.8%
32.0%
16.2%
86.3%

772
25.2%
59.6%
27.3%
29.1%
72.8%
7.1%
67.5%
33.9%
23.5%
85.6%
19.7%
65.4%
27.8%
20.2%
86.5%

773
26.4%
65.6%
23.9%
20.4%
80.9%
26.1%
75.3%
41.3%
33.7%
91.7%
25.4%
71.2%
33.4%
25.0%
92.7%

774
45.9%
60.8%
25.3%
16.9%
70.4%
31.0%
67.5%
51.4%
25.0%
86.1%
43.8%
66.5%
39.3%
18.7%
87.0%

775
34.5%
62.0%
25.6%
20.0%
68.5%
18.6%
66.5%
25.8%
15.7%
83.9%
25.3%
69.0%
24.8%
15.1%
83.9%

776
30.7%
59.5%
29.6%
14.1%
70.9%
11.6%
55.8%
40.5%
18.1%
85.4%
25.4%
62.2%
34.1%
16.5%
87.3%

777
27.1%
65.4%
24.3%
24.6%
75.1%
5.1%
72.0%
34.3%
27.0%
88.8%
21.2%
65.7%
24.7%
20.0%
88.6%

778
31.6%
59.8%
26.2%
16.4%
69.6%
11.0%
66.9%
43.2%
16.6%
86.1%
21.2%
66.1%
32.5%
15.8%
86.8%

779
45.7%
62.1%
27.0%
15.8%
69.4%
26.0%
65.4%
44.3%
18.6%
86.4%
37.5%
64.7%
31.7%
17.7%
85.2%

780
42.5%
64.0%
31.3%
19.7%
70.5%
12.9%
66.7%
31.7%
21.1%
84.5%
27.6%
69.7%
29.5%
18.0%
85.8%

781
28.4%
57.2%
30.4%
14.8%
66.5%
11.4%
64.1%
46.7%
23.8%
83.9%
22.4%
64.9%
39.2%
18.5%
84.5%

782
27.7%
61.3%
24.0%
20.4%
69.8%
8.1%
63.1%
24.0%
19.2%
84.8%
19.9%
61.0%
23.9%
18.5%
84.0%

783
23.5%
60.9%
28.8%
20.2%
70.1%
29.9%
62.7%
27.9%
13.9%
87.1%
29.3%
65.4%
27.9%
17.5%
88.2%

784
41.4%
60.0%
31.9%
16.5%
67.9%
19.2%
59.2%
40.8%
19.8%
83.0%
38.8%
64.3%
35.4%
17.8%
84.8%

785
37.5%
61.3%
28.4%
17.4%
68.8%
12.4%
66.7%
33.8%
23.4%
84.9%
30.3%
68.2%
26.9%
17.6%
86.5%

786
35.3%
66.7%
39.0%
10.8%
74.1%
11.4%
57.4%
33.5%
15.6%
82.4%
23.4%
60.3%
32.7%
12.8%
82.1%

787
20.3%
58.3%
26.4%
20.3%
65.5%
7.9%
60.8%
30.2%
25.2%
81.6%
19.6%
62.3%
26.9%
21.6%
82.6%

788
31.0%
60.6%
28.3%
16.3%
69.2%
6.8%
62.4%
47.3%
20.0%
84.0%
24.5%
66.9%
38.4%
18.3%
85.4%

789
39.1%
58.8%
34.5%
17.0%
66.1%
23.7%
60.1%
39.7%
26.6%
85.3%
35.6%
65.6%
37.9%
20.9%
86.1%

790
35.8%
59.0%
37.6%
20.8%
65.6%
8.2%
63.9%
42.0%
31.1%
83.5%
29.2%
65.8%
35.6%
21.3%
83.4%

791
29.0%
57.5%
39.0%
16.0%
65.1%
6.6%
54.7%
36.7%
23.0%
82.7%
27.4%
63.2%
35.3%
18.4%
84.0%

792
21.2%
58.0%
28.4%
18.5%
67.5%
8.4%
56.3%
38.3%
31.4%
79.1%
18.3%
61.8%
37.3%
28.9%
81.6%

793
27.2%
60.0%
39.8%
18.7%
67.8%
10.9%
60.7%
38.6%
21.4%
85.7%
21.8%
65.2%
34.8%
20.2%
86.7%

794
41.3%
61.9%
43.9%
23.5%
69.4%
15.0%
59.1%
42.8%
28.4%
84.1%
40.9%
68.6%
44.9%
23.8%
86.3%

795
44.3%
67.4%
49.7%
26.1%
74.6%
14.4%
65.7%
35.2%
33.6%
84.0%
31.2%
70.4%
40.3%
26.3%
86.2%

796
24.0%
54.8%
38.5%
17.9%
63.8%
8.6%
46.7%
31.1%
22.1%
81.8%
23.9%
60.3%
36.6%
19.0%
82.2%

797
24.7%
65.1%
33.6%
21.3%
72.0%
7.2%
61.1%
27.6%
24.6%
83.8%
23.3%
67.2%
31.7%
25.3%
85.4%

798
25.4%
58.0%
40.9%
19.2%
65.4%
11.5%
59.6%
40.1%
23.4%
83.0%
24.2%
64.2%
40.6%
22.0%
82.8%

799
39.5%
59.8%
42.9%
24.4%
67.2%
13.2%
56.5%
39.4%
29.1%
84.2%
37.8%
65.6%
44.8%
25.0%
84.8%

800
33.4%
57.4%
41.9%
33.6%
65.5%
8.7%
61.9%
36.3%
31.3%
84.8%
29.9%
63.4%
37.2%
28.9%
83.5%

801
28.7%
62.3%
43.3%
20.2%
70.7%
7.5%
61.4%
45.3%
31.8%
84.5%
25.8%
65.5%
41.8%
23.6%
85.9%

802
23.3%
62.3%
38.3%
26.3%
70.0%
9.8%
61.4%
48.0%
46.1%
85.0%
22.3%
66.2%
42.9%
37.0%
86.4%

803
29.0%
62.3%
44.1%
24.2%
69.2%
6.2%
65.9%
47.9%
27.8%
85.8%
27.2%
69.3%
46.1%
24.3%
86.5%

804
35.9%
60.0%
44.3%
30.4%
66.2%
28.4%
56.4%
27.5%
29.0%
84.3%
34.3%
65.1%
39.1%
28.6%
84.3%

805
37.6%
63.9%
49.1%
40.6%
70.7%
6.8%
66.9%
47.2%
40.6%
86.3%
32.2%
68.6%
43.0%
31.5%
85.6%

806
35.6%
70.1%
56.3%
34.5%
75.9%
10.8%
55.3%
41.2%
27.1%
88.4%
32.5%
69.6%
45.5%
24.5%
86.3%

807
29.1%
61.5%
42.0%
33.0%
68.2%
5.8%
61.6%
34.0%
30.6%
84.1%
30.5%
67.6%
35.1%
28.2%
84.4%

808
30.8%
61.5%
45.1%
28.5%
67.9%
7.9%
66.4%
45.4%
28.1%
87.0%
27.8%
67.0%
42.1%
22.5%
85.1%

809
41.9%
61.3%
45.4%
31.6%
68.0%
21.5%
65.9%
44.7%
30.8%
88.2%
38.5%
66.9%
41.2%
25.8%
86.5%

810
43.7%
66.0%
52.5%
44.9%
71.9%
8.4%
71.9%
31.3%
32.7%
88.5%
36.2%
72.3%
43.5%
35.7%
88.1%

811
36.0%
64.9%
48.9%
29.5%
71.0%
5.0%
53.5%
44.1%
31.2%
89.4%
29.2%
67.3%
38.3%
20.5%
85.1%

812
24.8%
61.0%
38.8%
32.4%
68.0%
5.6%
53.2%
24.9%
25.2%
86.5%
20.1%
68.0%
26.5%
22.1%
86.2%

813
33.4%
62.4%
46.4%
29.5%
68.9%
7.0%
72.1%
48.8%
28.9%
88.4%
27.8%
69.6%
44.4%
23.9%
85.5%

814
41.0%
59.7%
43.2%
30.0%
67.9%
25.4%
53.9%
32.7%
32.2%
85.3%
40.7%
67.1%
39.5%
27.8%
86.6%

815
48.3%
71.6%
57.9%
50.6%
76.9%
5.4%
71.9%
30.6%
24.4%
87.8%
32.5%
72.7%
41.8%
31.8%
88.2%

816
29.8%
60.9%
44.1%
29.8%
68.6%
8.0%
49.7%
36.7%
28.1%
86.0%
27.5%
64.6%
41.3%
22.6%
84.4%

817
29.2%
60.8%
42.3%
36.2%
68.3%
8.3%
50.9%
23.6%
27.1%
85.2%
22.9%
64.6%
33.0%
29.3%
84.1%

818
32.7%
67.2%
50.5%
33.2%
73.5%
10.2%
68.2%
35.1%
25.8%
88.4%
30.0%
70.2%
42.3%
25.1%
86.0%

819
36.5%
60.1%
43.6%
27.4%
67.8%
22.7%
53.1%
29.6%
26.9%
86.8%
32.7%
67.6%
38.4%
24.2%
86.7%

820
37.5%
66.6%
52.5%
43.0%
72.5%
7.4%
67.1%
28.9%
20.3%
86.7%
23.0%
72.4%
42.5%
28.8%
88.0%

821
29.9%
60.8%
45.5%
27.9%
68.0%
6.3%
63.5%
52.1%
35.6%
87.6%
17.9%
65.5%
43.2%
21.8%
83.8%

822
22.2%
61.1%
43.5%
25.9%
68.9%
6.3%
65.6%
39.4%
26.6%
87.5%
16.4%
67.3%
39.0%
22.5%
85.3%

823
42.1%
63.4%
46.2%
27.8%
70.4%
15.4%
49.9%
30.6%
33.8%
87.9%
34.6%
68.3%
41.8%
23.0%
86.3%

824
32.4%
64.3%
49.2%
39.9%
70.4%
7.7%
69.7%
28.1%
23.1%
86.3%
19.0%
69.9%
39.6%
28.4%
87.2%

825
23.0%
62.8%
48.1%
30.6%
69.9%
6.4%
66.0%
47.7%
26.7%
87.3%
17.2%
67.1%
46.3%
21.8%
86.2%

826
21.8%
60.4%
41.8%
34.2%
68.3%
4.1%
42.7%
19.4%
21.5%
82.9%
14.7%
63.7%
30.2%
23.6%
84.7%

827
22.2%
61.5%
43.7%
28.2%
69.3%
13.9%
59.4%
25.8%
19.3%
84.8%
19.3%
68.0%
39.1%
26.4%
86.5%

828
34.9%
60.9%
44.0%
26.8%
67.6%
35.6%
55.3%
28.1%
22.6%
86.0%
38.4%
66.4%
42.8%
23.9%
85.4%

829
28.7%
64.4%
49.7%
41.1%
70.7%
6.1%
68.3%
25.7%
20.7%
86.2%
18.0%
71.1%
42.5%
29.2%
86.4%

830
23.5%
60.1%
42.3%
25.1%
68.4%
11.5%
42.9%
30.2%
24.3%
87.0%
18.4%
66.1%
40.0%
22.0%
86.1%

831
22.4%
63.0%
42.3%
33.8%
70.5%
5.4%
59.7%
32.4%
30.6%
86.8%
17.5%
66.5%
34.1%
25.3%
85.4%

832
25.4%
68.5%
49.1%
30.2%
74.4%
8.2%
73.4%
42.0%
35.3%
92.2%
13.7%
76.2%
46.5%
31.8%
90.7%

833
37.5%
61.4%
41.3%
26.7%
68.4%
17.4%
53.5%
39.0%
32.9%
88.7%
40.3%
71.4%
44.2%
23.6%
87.9%

834
29.9%
59.8%
45.6%
37.1%
65.8%
7.4%
64.4%
23.7%
18.0%
84.2%
17.9%
68.8%
38.3%
27.3%
85.7%

835
23.5%
59.8%
44.6%
25.3%
66.9%
5.7%
55.5%
42.7%
26.6%
87.1%
17.0%
67.2%
45.0%
20.4%
87.7%

836
20.7%
62.1%
41.1%
32.6%
68.3%
9.4%
48.6%
29.7%
38.1%
86.4%
18.9%
69.0%
35.6%
31.1%
87.8%

837
22.4%
62.7%
46.9%
29.7%
70.0%
5.4%
61.3%
41.0%
28.7%
87.3%
15.9%
72.2%
45.1%
23.4%
88.1%

838
35.9%
62.8%
44.8%
28.5%
70.0%
34.9%
56.4%
30.3%
25.4%
87.8%
42.6%
69.7%
43.1%
26.7%
89.0%

839
29.9%
62.1%
47.0%
37.0%
67.4%
8.2%
66.6%
20.8%
18.1%
84.6%
18.3%
72.8%
29.7%
23.5%
86.5%

840
18.9%
61.9%
45.1%
30.9%
69.8%
13.6%
44.1%
27.2%
19.0%
85.9%
21.5%
65.1%
44.0%
24.0%
85.8%

841
20.5%
61.8%
43.7%
35.4%
69.7%
7.3%
56.6%
35.4%
41.8%
87.2%
18.3%
67.2%
41.7%
42.2%
88.3%

842
23.3%
63.4%
46.0%
31.1%
70.1%
5.2%
60.1%
37.6%
23.2%
86.0%
15.3%
68.3%
41.7%
23.3%
87.2%

843
46.9%
64.2%
45.2%
28.9%
70.7%
24.8%
48.6%
31.6%
26.5%
90.0%
48.7%
63.5%
35.3%
23.4%
90.3%

844
33.0%
62.0%
44.3%
34.6%
69.0%
8.3%
70.2%
26.9%
24.9%
87.8%
21.1%
74.4%
30.4%
25.4%
89.5%

845
24.2%
60.8%
42.5%
23.8%
68.8%
11.4%
42.2%
30.3%
25.1%
86.4%
18.8%
56.3%
38.2%
21.3%
86.2%

846
39.9%
60.8%
39.6%
25.1%
68.7%
31.5%
55.3%
31.6%
27.8%
88.5%
46.7%
63.7%
33.8%
26.9%
89.1%

847
36.0%
63.2%
46.6%
37.7%
69.6%
5.2%
67.5%
23.7%
19.7%
85.8%
20.0%
73.0%
25.6%
18.9%
86.9%

848
29.1%
65.2%
48.1%
19.8%
72.4%
5.1%
48.6%
45.2%
24.1%
88.6%
17.8%
59.1%
44.7%
17.7%
90.5%

849
22.0%
62.1%
33.4%
27.7%
68.8%
5.0%
62.3%
35.6%
33.9%
87.6%
16.9%
65.8%
33.5%
27.5%
87.0%

850
28.2%
65.4%
43.7%
26.2%
71.6%
13.2%
63.2%
29.1%
20.9%
91.1%
19.9%
68.3%
30.0%
20.9%
91.7%

851
60.4%
74.1%
45.2%
25.8%
79.3%
44.5%
63.3%
54.1%
54.6%
91.6%
60.0%
75.6%
54.5%
47.3%
91.4%

852
38.9%
62.3%
40.3%
31.4%
69.0%
8.7%
71.1%
21.7%
20.5%
86.8%
22.6%
73.9%
24.4%
19.9%
88.1%

853
33.4%
72.4%
52.3%
21.9%
78.9%
7.5%
39.5%
28.1%
15.6%
87.0%
18.6%
51.9%
30.9%
14.5%
90.1%

854
25.2%
66.5%
36.9%
33.5%
73.3%
4.8%
45.0%
17.6%
24.9%
86.0%
17.3%
59.4%
24.7%
30.1%
88.6%

855
35.5%
72.8%
44.0%
21.9%
77.7%
4.6%
58.9%
32.4%
22.7%
93.7%
16.8%
63.1%
29.4%
19.6%
93.3%

856
47.5%
65.4%
40.6%
21.6%
72.0%
19.2%
59.4%
42.9%
31.9%
88.9%
50.5%
70.6%
45.3%
26.3%
89.8%

857
45.6%
68.5%
42.3%
32.5%
74.4%
9.4%
72.5%
24.1%
19.6%
87.0%
24.3%
72.8%
27.4%
19.5%
86.7%

858
26.5%
56.0%
37.0%
16.5%
63.4%
6.5%
40.2%
28.3%
20.3%
82.8%
21.1%
57.5%
33.7%
17.7%
83.9%

859
24.2%
60.8%
36.2%
31.0%
68.3%
9.0%
57.2%
22.4%
26.0%
86.6%
19.7%
65.6%
27.9%
28.5%
87.5%

860
32.7%
63.6%
37.2%
21.0%
70.3%
8.8%
59.4%
27.8%
26.2%
87.2%
25.6%
63.6%
30.5%
21.6%
86.9%

861
50.1%
67.3%
41.1%
24.6%
74.6%
23.5%
53.3%
35.0%
30.5%
90.4%
53.8%
68.5%
40.6%
25.7%
92.8%

862
43.0%
64.5%
41.9%
34.4%
70.6%
7.1%
75.8%
25.2%
22.6%
90.1%
29.2%
77.8%
25.5%
20.1%
89.7%

863
37.0%
70.0%
50.0%
20.9%
75.7%
6.3%
36.9%
29.0%
15.3%
88.1%
21.2%
63.0%
39.8%
16.3%
90.4%

864
28.1%
65.0%
34.5%
31.6%
71.9%
7.4%
59.2%
32.8%
38.1%
88.5%
21.6%
67.9%
34.5%
32.6%
88.4%

865
31.1%
61.9%
37.9%
21.8%
68.9%
7.6%
60.0%
34.2%
23.9%
86.0%
21.1%
65.6%
34.5%
21.3%
87.5%

866
41.3%
60.1%
33.1%
21.8%
69.5%
29.5%
57.9%
33.0%
25.5%
88.1%
45.1%
67.5%
36.4%
23.6%
88.6%

867
34.1%
63.3%
35.6%
29.2%
69.7%
9.2%
71.9%
27.6%
22.7%
88.0%
24.3%
75.5%
29.7%
22.9%
89.4%

868
25.0%
59.1%
37.7%
17.0%
69.5%
5.1%
46.5%
33.1%
22.1%
87.0%
22.6%
61.6%
34.1%
15.2%
86.6%

869
23.8%
62.0%
31.6%
29.4%
70.9%
5.5%
56.5%
33.5%
40.0%
87.8%
21.4%
67.8%
31.6%
32.4%
89.4%

870
27.4%
64.3%
38.2%
25.1%
73.2%
6.9%
62.4%
31.5%
21.1%
89.3%
22.8%
66.7%
32.1%
20.9%
89.8%

871
43.8%
77.8%
29.7%
6.8%
85.0%
23.0%
31.7%
18.5%
14.8%
90.1%
26.2%
49.0%
19.5%
11.1%
91.5%

872
27.5%
73.1%
22.7%
11.7%
78.8%
8.9%
66.5%
26.1%
20.3%
86.2%
16.9%
72.9%
24.2%
16.5%
88.9%

873
16.7%
76.1%
44.3%
6.5%
86.5%
4.0%
23.6%
17.8%
12.3%
89.1%
12.4%
38.5%
22.5%
10.9%
91.3%

874
10.6%
82.7%
16.2%
6.9%
87.4%
3.5%
23.3%
10.4%
16.4%
89.0%
9.4%
49.5%
14.0%
14.2%
91.4%

875
27.9%
69.9%
27.0%
9.0%
82.1%
4.9%
33.5%
17.3%
15.4%
85.9%
14.1%
50.1%
22.2%
15.8%
89.7%

876
42.7%
70.5%
28.2%
11.4%
78.3%
21.7%
40.3%
26.3%
18.5%
86.5%
26.0%
49.9%
24.2%
15.0%
88.8%

877
19.0%
71.0%
28.1%
13.3%
78.9%
5.6%
52.5%
18.9%
13.5%
85.8%
13.5%
69.4%
20.7%
13.6%
90.0%

878
21.0%
64.4%
41.0%
10.8%
75.8%
6.4%
38.3%
29.3%
17.9%
82.6%
14.5%
43.6%
28.3%
14.4%
84.9%

879
14.2%
71.6%
21.3%
11.9%
78.1%
5.2%
35.8%
18.5%
22.2%
86.6%
11.0%
47.6%
17.5%
15.2%
86.5%

880
17.0%
78.6%
30.3%
7.6%
85.8%
8.5%
70.1%
34.1%
19.5%
92.6%
11.8%
60.2%
24.4%
14.2%
92.3%

881
42.7%
63.8%
32.3%
23.4%
74.7%
21.1%
47.6%
23.6%
20.2%
85.3%
32.0%
49.9%
25.1%
17.6%
86.8%

882
22.0%
69.7%
39.1%
25.1%
75.7%
6.3%
63.0%
20.7%
15.1%
83.8%
14.8%
64.2%
23.6%
14.7%
86.6%

883
23.5%
65.5%
45.8%
17.3%
75.1%
6.7%
32.9%
20.9%
15.7%
81.9%
15.7%
44.4%
24.3%
14.0%
84.5%

884
18.8%
79.0%
29.0%
33.8%
88.3%
3.8%
33.8%
11.8%
17.1%
89.9%
10.0%
41.0%
14.1%
15.3%
91.8%

885
21.8%
69.1%
37.5%
19.1%
76.8%
7.5%
53.3%
25.1%
17.4%
85.4%
14.0%
54.6%
25.0%
16.4%
87.3%

886
39.5%
63.8%
35.9%
32.6%
77.3%
21.6%
42.6%
24.7%
16.1%
86.3%
31.0%
46.9%
21.9%
15.3%
86.6%

887
36.0%
71.7%
21.8%
20.9%
78.1%
6.8%
72.5%
20.7%
11.9%
87.8%
21.3%
71.6%
19.6%
12.5%
88.5%

888
19.9%
58.0%
38.8%
14.4%
81.8%
5.6%
28.8%
20.9%
12.0%
87.0%
15.2%
41.6%
22.2%
11.4%
88.4%

889
17.5%
55.8%
26.5%
30.7%
73.3%
5.8%
45.4%
20.4%
19.8%
83.7%
17.0%
50.4%
22.3%
18.8%
84.1%

890
22.6%
65.0%
31.1%
22.3%
75.9%
7.0%
47.0%
21.2%
16.7%
85.3%
16.2%
53.7%
24.2%
14.5%
86.5%

891
48.7%
66.0%
27.0%
23.6%
76.6%
23.3%
41.3%
21.8%
18.0%
87.9%
43.5%
51.7%
22.4%
15.6%
89.2%

892
39.1%
77.4%
22.3%
22.7%
82.2%
15.8%
75.8%
22.5%
33.0%
89.9%
21.2%
78.9%
21.0%
20.7%
90.0%

893
24.6%
50.6%
28.3%
12.6%
75.0%
7.2%
40.7%
30.3%
23.2%
88.8%
20.0%
43.3%
23.4%
14.2%
86.6%

894
17.9%
69.3%
27.5%
38.5%
81.7%
5.6%
41.6%
17.2%
21.2%
88.1%
14.6%
49.1%
17.4%
17.8%
89.2%

895
26.0%
58.0%
21.2%
20.2%
78.6%
9.6%
74.7%
47.8%
24.0%
90.3%
19.0%
60.9%
29.5%
17.5%
90.6%

896
49.6%
63.0%
25.9%
19.6%
72.8%
24.3%
46.7%
20.5%
14.6%
85.2%
41.8%
55.8%
26.1%
15.6%
87.6%

897
32.9%
62.4%
22.2%
18.7%
71.8%
25.8%
73.2%
34.5%
29.9%
88.8%
29.6%
73.4%
26.3%
17.5%
88.0%

898
27.7%
57.6%
29.9%
14.0%
74.4%
9.4%
44.3%
29.5%
16.7%
84.7%
21.6%
53.6%
30.4%
15.1%
86.7%

899
25.4%
56.1%
23.5%
28.0%
72.7%
6.6%
55.7%
19.1%
17.2%
86.4%
22.3%
55.2%
23.9%
19.4%
86.5%

900
30.9%
52.7%
24.0%
19.1%
70.6%
9.6%
70.1%
54.7%
36.9%
87.8%
23.4%
63.7%
34.9%
22.6%
87.3%

901
42.7%
58.7%
26.1%
16.5%
70.3%
32.7%
58.1%
28.6%
16.4%
85.8%
35.5%
59.0%
26.8%
18.1%
86.2%

902
34.4%
62.0%
23.4%
19.3%
70.0%
10.5%
66.3%
23.7%
16.0%
85.0%
25.8%
67.6%
24.3%
15.7%
86.0%

903
28.9%
60.2%
31.4%
13.6%
74.0%
7.3%
54.4%
36.3%
21.0%
86.5%
25.1%
56.5%
31.2%
15.9%
87.5%

904
30.1%
60.5%
24.2%
21.7%
72.3%
6.6%
58.2%
20.3%
19.0%
85.9%
21.4%
60.2%
23.2%
17.2%
86.5%

905
30.2%
56.7%
24.9%
15.7%
68.5%
8.5%
61.8%
33.9%
19.7%
86.0%
22.9%
60.8%
28.1%
18.4%
86.7%

906
56.2%
68.8%
29.4%
14.8%
76.3%
38.3%
69.4%
51.6%
22.7%
87.7%
49.3%
69.4%
34.2%
16.4%
88.6%

907
37.0%
63.2%
31.5%
20.6%
70.5%
13.5%
64.2%
23.8%
15.5%
84.2%
27.3%
68.2%
27.1%
18.9%
86.0%

908
29.0%
59.4%
31.5%
13.9%
72.0%
9.2%
53.1%
33.6%
18.5%
84.3%
25.7%
57.6%
29.7%
15.7%
86.1%

909
28.0%
64.3%
26.3%
21.1%
72.0%
8.5%
60.7%
24.8%
19.7%
85.3%
21.1%
65.3%
27.1%
19.8%
86.6%

910
35.3%
65.2%
24.7%
15.9%
74.4%
13.4%
70.8%
55.7%
23.9%
87.9%
28.1%
72.9%
42.2%
18.2%
88.4%

911
44.7%
62.6%
27.5%
16.0%
71.0%
30.3%
60.6%
35.3%
30.4%
85.1%
41.7%
65.1%
30.5%
20.1%
86.5%

912
35.6%
60.2%
40.3%
23.3%
66.9%
8.6%
60.9%
26.8%
18.5%
82.7%
24.6%
66.9%
32.4%
19.9%
84.5%

913
34.0%
64.7%
35.8%
14.4%
73.2%
8.0%
55.2%
40.3%
21.8%
84.3%
25.0%
63.4%
33.6%
17.3%
85.2%

914
25.4%
60.2%
26.5%
20.8%
67.9%
5.7%
55.5%
22.2%
21.4%
81.0%
20.6%
65.9%
27.8%
21.5%
84.7%

915
32.1%
61.7%
34.5%
16.9%
69.1%
7.4%
59.2%
37.0%
19.9%
83.5%
24.0%
67.8%
35.2%
19.8%
86.8%

916
44.8%
62.9%
40.0%
16.3%
68.9%
20.5%
63.3%
49.8%
35.5%
84.3%
40.3%
66.0%
42.0%
21.7%
84.3%

917
32.9%
60.0%
40.6%
22.3%
67.5%
9.5%
62.4%
36.4%
31.0%
84.5%
24.6%
65.7%
37.5%
22.3%
84.6%

918
23.2%
59.3%
33.0%
21.1%
67.2%
6.7%
65.2%
47.2%
40.3%
85.7%
22.7%
66.1%
36.7%
27.9%
84.9%

919
26.1%
58.5%
38.4%
16.4%
66.9%
8.3%
59.1%
38.0%
22.7%
81.6%
22.7%
64.0%
36.1%
18.3%
83.0%

920
40.8%
63.8%
48.0%
32.7%
71.3%
10.0%
64.7%
32.4%
24.5%
85.2%
27.5%
70.0%
43.3%
28.9%
86.6%

921
37.9%
67.7%
50.5%
17.6%
74.2%
7.0%
55.6%
36.7%
24.1%
86.5%
30.8%
65.7%
41.6%
18.0%
86.3%

922
25.5%
62.8%
41.7%
27.9%
70.0%
5.8%
55.0%
26.8%
28.4%
85.2%
21.3%
68.2%
38.0%
29.1%
86.8%

923
29.6%
61.5%
46.2%
20.3%
69.4%
8.0%
62.1%
38.9%
23.3%
83.9%
22.7%
65.6%
39.7%
18.9%
84.4%

924
41.9%
61.3%
44.5%
25.8%
68.0%
24.6%
58.1%
33.3%
23.5%
86.4%
37.0%
66.8%
44.0%
26.4%
84.6%

925
37.6%
61.5%
46.7%
37.4%
67.5%
6.6%
65.2%
38.2%
35.3%
85.0%
30.1%
68.1%
40.9%
29.0%
84.7%

926
28.7%
59.6%
43.2%
26.1%
68.7%
6.4%
51.2%
35.2%
34.2%
84.0%
25.4%
63.8%
39.8%
24.1%
86.6%

927
24.3%
61.1%
40.4%
29.8%
68.7%
6.3%
66.3%
34.3%
31.4%
86.0%
22.6%
67.4%
39.8%
31.3%
84.9%

928
28.0%
58.4%
37.5%
21.5%
68.5%
24.1%
57.3%
34.1%
15.9%
82.0%
28.7%
62.4%
36.7%
20.1%
83.0%

929
41.4%
62.2%
47.4%
31.1%
69.8%
38.5%
64.9%
40.2%
23.0%
87.2%
42.8%
70.0%
45.8%
27.8%
87.0%

930
47.4%
71.6%
60.1%
51.8%
76.5%
8.3%
69.0%
23.9%
17.3%
87.6%
29.9%
73.6%
41.5%
29.8%
88.4%

931
31.5%
58.3%
41.3%
28.7%
67.5%
6.7%
40.7%
28.7%
24.0%
83.3%
24.9%
66.9%
40.0%
23.5%
86.6%

932
28.3%
61.9%
44.9%
35.9%
68.3%
5.6%
54.5%
24.8%
27.8%
86.3%
25.0%
68.1%
36.2%
31.9%
85.7%

933
29.3%
62.9%
46.1%
25.2%
70.4%
9.5%
61.0%
29.3%
20.3%
86.2%
25.9%
70.0%
39.1%
22.0%
87.2%

934
61.7%
75.6%
63.1%
43.4%
80.1%
26.0%
58.1%
34.5%
25.9%
90.7%
55.7%
77.2%
50.2%
27.1%
90.8%

935
41.7%
66.4%
53.0%
46.6%
72.7%
9.3%
77.6%
26.7%
20.2%
90.3%
20.0%
72.9%
49.0%
38.2%
87.6%

936
31.8%
60.9%
46.9%
29.5%
68.7%
5.5%
51.3%
38.9%
27.9%
84.9%
22.0%
65.5%
41.0%
19.4%
84.5%

937
32.6%
61.2%
43.0%
38.9%
68.5%
5.2%
66.2%
45.0%
42.0%
87.3%
25.6%
66.0%
38.7%
31.7%
84.6%

938
32.4%
64.1%
45.3%
31.8%
72.2%
10.6%
65.6%
37.4%
28.8%
88.7%
24.3%
66.8%
40.3%
25.9%
88.0%

939
41.9%
60.7%
42.8%
32.6%
67.8%
21.6%
59.8%
29.7%
44.6%
86.8%
44.5%
68.9%
38.7%
31.7%
86.0%

940
37.4%
62.9%
46.1%
40.7%
69.5%
10.8%
69.4%
31.7%
31.1%
86.1%
30.5%
70.6%
42.7%
33.9%
88.1%

941
29.1%
60.4%
42.4%
35.3%
68.1%
6.2%
50.3%
25.0%
28.1%
85.9%
21.3%
66.4%
31.0%
25.3%
85.5%

942
31.3%
63.1%
46.3%
31.4%
70.0%
5.5%
68.8%
45.4%
36.6%
87.7%
22.6%
66.4%
43.4%
26.4%
84.5%

943
48.7%
66.0%
50.6%
33.9%
72.4%
32.7%
60.6%
35.7%
28.5%
90.9%
47.8%
74.5%
49.8%
25.8%
89.6%

944
39.3%
70.2%
57.9%
51.7%
75.3%
7.2%
74.2%
29.5%
24.0%
90.1%
19.2%
72.0%
49.8%
38.8%
87.4%

945
26.2%
58.4%
42.1%
25.5%
66.2%
6.7%
42.6%
29.9%
22.4%
84.6%
18.1%
63.9%
38.9%
20.0%
85.1%

946
23.8%
58.8%
42.0%
35.1%
66.7%
5.2%
47.0%
20.4%
23.6%
86.0%
15.6%
62.9%
32.0%
26.1%
84.1%

947
27.1%
64.0%
47.8%
31.8%
70.8%
7.3%
59.9%
30.6%
23.6%
87.5%
18.8%
68.3%
41.8%
22.5%
85.9%

948
47.6%
68.6%
54.5%
36.4%
74.3%
24.3%
39.9%
21.6%
17.1%
87.3%
33.3%
69.2%
46.1%
25.1%
86.8%

949
29.8%
62.8%
48.1%
40.2%
70.1%
8.8%
69.2%
42.1%
44.0%
86.4%
18.4%
71.7%
45.7%
34.6%
87.6%

950
21.5%
62.4%
48.3%
30.4%
69.8%
5.9%
37.2%
27.5%
19.9%
85.8%
17.8%
64.0%
42.3%
20.9%
85.8%

951
27.4%
62.0%
45.0%
38.4%
69.1%
4.8%
50.5%
24.8%
26.6%
83.8%
16.6%
66.1%
35.7%
27.4%
83.9%

952
25.0%
66.0%
47.7%
27.9%
72.8%
5.4%
64.5%
41.3%
35.3%
88.0%
16.4%
71.7%
42.9%
22.4%
88.6%

953
43.9%
64.9%
50.0%
31.4%
71.6%
30.0%
45.0%
22.7%
33.8%
90.5%
37.2%
69.0%
46.9%
24.3%
86.1%

954
31.6%
66.0%
51.9%
43.5%
72.2%
5.9%
69.1%
22.3%
18.0%
87.6%
15.8%
72.0%
44.7%
34.0%
87.8%

955
22.1%
61.0%
44.1%
27.4%
70.6%
13.6%
45.2%
27.0%
16.0%
88.4%
18.6%
65.9%
41.7%
19.3%
88.2%

956
22.2%
61.3%
43.2%
35.0%
69.0%
5.4%
43.4%
19.4%
22.2%
86.0%
13.3%
66.2%
35.3%
27.9%
85.0%

957
21.7%
67.0%
51.8%
31.5%
73.3%
7.6%
58.6%
28.6%
22.7%
89.0%
15.4%
70.8%
45.1%
23.8%
87.6%

958
30.3%
62.5%
46.8%
40.5%
69.1%
5.9%
67.3%
29.2%
21.3%
85.5%
18.9%
71.8%
43.0%
32.9%
87.7%

959
23.0%
61.7%
46.3%
31.4%
69.5%
6.3%
34.9%
23.6%
17.0%
85.5%
16.7%
65.6%
41.7%
19.4%
88.0%

960
20.9%
61.1%
43.8%
34.4%
68.9%
6.5%
46.1%
19.2%
22.6%
85.5%
14.6%
68.2%
39.8%
35.3%
86.6%

961
22.3%
67.4%
52.3%
33.9%
73.8%
4.3%
55.0%
29.9%
30.7%
89.8%
13.6%
77.1%
51.0%
31.1%
91.0%

962
40.9%
57.8%
43.7%
27.8%
65.2%
18.7%
42.2%
22.4%
18.0%
84.4%
35.8%
66.4%
39.5%
20.9%
85.7%

963
31.8%
64.0%
49.5%
41.1%
70.8%
7.7%
68.4%
22.4%
16.9%
87.0%
18.4%
73.4%
43.1%
28.3%
88.3%

964
24.7%
61.3%
45.3%
29.5%
69.4%
6.1%
36.7%
23.8%
18.6%
84.7%
17.2%
62.4%
40.1%
17.3%
88.0%

965
22.2%
62.1%
43.2%
35.5%
69.6%
5.5%
48.0%
24.0%
32.4%
85.4%
14.7%
68.7%
36.5%
33.8%
87.0%

966
23.8%
61.0%
45.8%
30.6%
67.9%
5.6%
51.4%
24.9%
18.9%
85.2%
16.6%
66.6%
38.6%
25.6%
86.5%

967
59.2%
73.7%
61.1%
35.0%
78.5%
22.3%
45.5%
29.0%
27.4%
89.9%
53.2%
73.8%
47.2%
25.4%
91.6%

968
32.6%
63.9%
47.1%
35.9%
71.0%
8.5%
68.6%
25.9%
25.2%
87.0%
19.2%
73.0%
30.2%
23.2%
87.7%

969
25.2%
62.2%
45.9%
26.8%
68.9%
7.4%
36.8%
24.8%
17.2%
84.8%
17.9%
59.9%
37.5%
18.3%
88.2%

970
21.4%
59.4%
38.6%
31.5%
67.4%
4.7%
46.4%
23.5%
27.0%
85.8%
17.0%
61.5%
34.0%
36.3%
87.3%

971
47.8%
65.7%
44.9%
29.1%
72.0%
29.4%
51.6%
24.3%
48.8%
89.0%
51.5%
68.3%
31.6%
39.9%
91.5%

972
43.6%
67.3%
51.4%
40.8%
73.1%
12.8%
71.4%
31.6%
23.4%
87.8%
26.6%
74.5%
29.8%
22.3%
89.5%

973
25.2%
59.2%
43.6%
24.4%
68.3%
5.9%
50.9%
37.2%
29.3%
85.9%
20.4%
59.5%
37.8%
22.5%
86.2%

974
23.4%
65.7%
39.8%
32.8%
72.9%
3.2%
39.0%
15.7%
26.3%
88.1%
16.9%
64.7%
24.6%
29.6%
90.7%

975
28.5%
67.5%
41.3%
24.8%
73.3%
6.0%
68.6%
29.3%
45.2%
90.0%
22.6%
71.1%
31.0%
38.6%
91.1%

976
50.2%
65.5%
40.0%
23.9%
71.3%
60.4%
66.5%
36.1%
14.6%
89.0%
58.7%
71.8%
37.1%
19.9%
89.4%

977
54.3%
76.7%
54.5%
44.6%
80.9%
5.2%
71.1%
19.4%
15.4%
87.8%
25.1%
81.0%
22.2%
16.4%
91.2%

978
32.8%
66.3%
48.7%
20.1%
73.4%
4.4%
30.8%
21.9%
13.2%
86.2%
21.9%
53.3%
30.3%
13.2%
89.8%

979
28.0%
64.0%
35.2%
30.2%
71.1%
5.2%
52.5%
33.6%
36.9%
86.1%
23.1%
65.2%
31.4%
33.1%
88.3%

980
32.0%
66.8%
42.0%
24.6%
72.8%
42.1%
76.9%
35.5%
13.8%
91.4%
38.9%
78.4%
33.9%
16.9%
91.9%

981
39.9%
62.8%
40.4%
31.2%
69.3%
7.3%
68.3%
26.0%
20.5%
86.7%
26.2%
68.1%
29.1%
19.9%
85.7%

982
29.7%
60.3%
41.5%
17.4%
68.1%
5.2%
36.8%
26.5%
18.5%
86.1%
23.2%
62.6%
33.2%
14.2%
86.6%

983
28.4%
64.9%
36.8%
29.9%
71.5%
3.4%
50.6%
25.1%
27.8%
87.4%
23.6%
69.2%
29.5%
26.8%
89.9%

984
30.9%
62.5%
37.6%
21.0%
69.9%
5.5%
58.0%
32.5%
28.3%
86.9%
21.6%
64.8%
33.3%
23.2%
87.9%

985
51.1%
66.8%
45.2%
25.6%
72.3%
29.7%
45.2%
25.9%
18.1%
87.3%
52.8%
69.7%
34.2%
20.1%
88.2%

986
46.4%
68.9%
45.7%
37.5%
74.9%
7.3%
71.0%
28.6%
26.9%
87.4%
29.9%
76.8%
32.3%
25.1%
89.5%

987
34.1%
63.8%
46.0%
21.3%
70.6%
5.6%
35.1%
25.1%
16.6%
84.5%
23.9%
58.9%
33.3%
14.8%
86.1%

988
31.3%
67.0%
39.6%
33.4%
73.1%
5.3%
45.8%
20.2%
24.4%
88.7%
25.4%
69.9%
25.8%
25.1%
89.2%

989
37.3%
66.9%
44.2%
24.5%
72.8%
5.0%
51.0%
25.4%
17.6%
85.2%
25.0%
64.9%
30.1%
18.5%
88.8%

990
42.0%
60.9%
33.3%
24.4%
70.8%
21.3%
47.2%
27.3%
20.8%
88.2%
47.2%
66.3%
32.2%
23.8%
90.3%

991
36.7%
65.7%
38.3%
31.9%
72.6%
8.5%
66.6%
22.8%
14.9%
86.3%
24.8%
75.0%
30.7%
23.6%
90.3%

992
28.2%
60.1%
38.3%
19.1%
69.5%
7.5%
44.4%
34.3%
21.6%
87.2%
22.6%
62.9%
37.0%
19.6%
88.6%

993
25.5%
62.9%
36.0%
32.9%
71.7%
5.8%
53.1%
24.9%
30.7%
87.7%
18.8%
67.3%
31.5%
31.8%
89.1%

994
29.4%
62.5%
35.6%
24.5%
72.0%
7.9%
56.9%
29.2%
24.6%
88.2%
23.8%
67.3%
32.8%
25.1%
90.4%

995
40.2%
67.3%
29.8%
11.2%
75.9%
15.5%
28.9%
15.4%
14.8%
86.1%
23.2%
43.1%
20.2%
15.1%
88.2%

996
37.0%
75.2%
21.0%
14.6%
81.5%
5.2%
56.2%
15.8%
11.8%
88.0%
15.5%
63.1%
19.6%
11.9%
90.3%

997
14.8%
68.9%
23.0%
13.9%
76.5%
6.5%
50.5%
19.1%
18.5%
85.6%
13.7%
60.8%
22.9%
17.6%
88.4%

998
17.7%
66.7%
33.9%
13.6%
75.6%
8.2%
40.6%
20.1%
16.7%
87.3%
15.6%
52.5%
26.6%
16.8%
88.4%

999
27.2%
62.5%
31.4%
19.5%
75.5%
14.7%
36.9%
18.1%
14.8%
86.2%
21.4%
47.6%
24.7%
17.5%
87.7%

1000
29.1%
70.0%
36.0%
26.1%
76.5%
12.0%
65.3%
24.3%
17.0%
85.6%
18.5%
71.0%
25.5%
16.6%
88.8%

1001
23.8%
64.1%
45.7%
19.6%
73.8%
6.9%
38.4%
27.0%
18.3%
83.2%
18.8%
51.9%
29.9%
18.0%
87.7%

1002
25.6%
80.9%
37.4%
39.2%
87.1%
4.7%
43.1%
19.4%
29.9%
89.9%
13.7%
53.3%
20.4%
28.7%
92.1%

1003
19.1%
67.7%
45.5%
17.3%
76.6%
6.2%
44.9%
20.8%
15.6%
86.4%
14.8%
53.9%
26.3%
16.3%
87.3%

1004
26.0%
68.2%
34.7%
34.0%
75.1%
19.9%
68.8%
30.3%
23.0%
86.5%
19.8%
67.6%
26.1%
18.7%
87.3%

1005
22.4%
63.1%
46.6%
26.2%
77.9%
6.9%
35.2%
23.9%
14.2%
85.6%
17.3%
48.6%
27.3%
15.3%
86.9%

1006
15.4%
62.5%
41.9%
43.2%
73.8%
6.5%
43.0%
19.4%
18.7%
84.9%
14.7%
53.5%
25.5%
23.4%
86.3%

1007
23.1%
60.2%
35.6%
30.6%
74.0%
6.9%
42.8%
21.9%
30.7%
85.0%
16.2%
49.0%
26.4%
22.5%
86.8%

1008
51.4%
62.4%
27.9%
26.6%
76.6%
26.9%
40.5%
20.6%
15.3%
86.3%
41.3%
51.5%
23.5%
16.5%
89.2%

1009
26.8%
57.7%
24.0%
21.8%
67.6%
8.6%
61.9%
20.6%
16.3%
84.5%
19.6%
65.0%
25.0%
17.3%
86.2%

1010
25.4%
62.4%
38.3%
17.1%
77.6%
7.3%
37.2%
31.0%
21.4%
86.4%
18.2%
50.2%
29.3%
15.4%
87.7%

1011
19.5%
63.0%
27.2%
37.9%
75.8%
5.1%
38.8%
16.9%
22.5%
86.0%
16.2%
49.7%
21.6%
21.1%
87.5%

1012
26.7%
60.1%
25.0%
25.6%
81.0%
17.3%
64.0%
31.0%
16.2%
89.8%
18.2%
57.8%
25.1%
14.7%
90.4%

1013
41.3%
58.2%
25.6%
20.3%
71.6%
29.9%
57.1%
31.1%
19.1%
85.9%
36.2%
56.9%
27.6%
18.2%
86.8%

1014
38.4%
65.7%
26.5%
26.7%
73.8%
9.4%
65.7%
23.4%
16.3%
85.5%
20.4%
68.5%
25.3%
17.0%
87.1%

1015
38.2%
61.4%
30.6%
13.2%
78.2%
11.5%
36.6%
25.8%
14.2%
88.1%
23.5%
49.8%
27.6%
13.4%
88.1%

1016
34.1%
65.2%
22.6%
26.5%
76.2%
8.7%
60.4%
28.6%
29.7%
88.1%
21.2%
64.0%
24.7%
23.1%
89.1%

1017
26.5%
57.6%
24.9%
18.2%
69.7%
11.9%
55.6%
25.1%
17.8%
85.5%
19.5%
58.3%
26.4%
18.3%
86.7%

1018
36.1%
60.4%
27.6%
20.6%
68.1%
9.7%
61.3%
26.0%
16.7%
83.7%
25.8%
66.5%
27.5%
19.3%
86.0%

1019
33.8%
56.5%
29.0%
14.0%
72.8%
17.5%
56.2%
36.5%
23.9%
87.0%
29.2%
57.0%
30.6%
16.9%
87.3%

1020
35.2%
61.7%
23.7%
19.5%
72.0%
7.9%
51.3%
18.9%
20.5%
86.3%
22.8%
60.9%
25.3%
19.9%
85.8%

1021
35.2%
52.6%
24.7%
16.3%
68.0%
11.4%
57.9%
30.6%
35.0%
85.4%
22.2%
53.1%
28.4%
22.9%
85.9%

1022
39.6%
60.5%
27.5%
19.5%
69.6%
32.1%
60.4%
35.5%
23.1%
86.9%
36.5%
66.6%
34.8%
21.7%
87.5%

1023
37.1%
60.3%
28.4%
19.3%
68.5%
21.3%
62.9%
31.7%
29.0%
84.4%
31.9%
69.7%
32.4%
20.6%
86.8%

1024
27.8%
54.2%
29.7%
14.5%
67.5%
14.8%
49.0%
28.1%
17.2%
81.1%
25.3%
55.9%
30.8%
16.4%
83.2%

1025
32.3%
59.6%
26.3%
21.0%
69.4%
6.5%
57.0%
21.4%
20.0%
81.8%
23.2%
61.6%
25.9%
20.9%
85.6%

1026
31.7%
60.3%
30.8%
16.6%
69.0%
10.9%
64.5%
35.2%
18.2%
84.0%
26.0%
66.9%
30.1%
17.2%
86.4%

1027
38.4%
60.9%
32.5%
19.0%
69.2%
26.2%
54.3%
28.2%
21.9%
84.9%
33.4%
64.6%
31.9%
20.9%
88.2%

1028
37.5%
61.0%
34.7%
21.2%
68.5%
8.9%
57.0%
25.6%
17.7%
81.9%
25.4%
65.6%
30.9%
20.2%
86.5%

1029
38.9%
64.2%
37.0%
15.3%
73.7%
7.8%
53.2%
38.9%
22.6%
87.1%
28.3%
64.0%
36.3%
18.0%
87.1%

1030
32.8%
57.7%
23.7%
18.4%
69.6%
6.9%
60.4%
25.3%
22.3%
85.1%
21.9%
63.2%
27.2%
21.8%
88.4%

1031
32.6%
58.8%
33.3%
17.1%
66.7%
8.6%
57.2%
35.0%
21.0%
83.0%
22.6%
65.2%
32.2%
18.6%
85.2%

1032
41.4%
60.5%
38.5%
17.7%
68.8%
28.7%
58.6%
37.0%
23.7%
84.6%
37.2%
65.8%
38.5%
20.8%
86.2%

1033
38.5%
63.5%
45.0%
25.4%
71.1%
8.5%
62.0%
34.6%
30.3%
84.1%
26.1%
69.4%
41.3%
25.8%
87.7%

1034
27.1%
59.6%
26.5%
18.6%
67.3%
7.8%
58.6%
29.1%
26.3%
82.4%
22.5%
65.2%
30.5%
21.2%
85.3%

1035
30.5%
57.5%
37.0%
17.7%
66.3%
6.3%
50.2%
28.1%
32.5%
82.8%
16.6%
61.9%
34.1%
23.4%
85.3%

1036
38.7%
58.3%
40.3%
19.6%
66.2%
16.4%
53.3%
32.2%
24.3%
83.3%
32.3%
64.2%
37.9%
21.4%
84.4%

1037
41.0%
63.4%
47.1%
36.5%
69.4%
7.9%
59.9%
26.3%
19.7%
82.6%
20.3%
66.3%
34.5%
23.0%
83.5%

1038
29.1%
57.1%
38.1%
17.3%
65.0%
11.6%
59.4%
38.0%
27.2%
83.3%
23.2%
59.7%
37.2%
20.2%
82.0%

1039
31.9%
64.7%
35.0%
24.1%
71.5%
5.5%
55.9%
34.3%
35.3%
85.0%
21.1%
66.7%
34.8%
28.5%
86.0%

1040
33.7%
61.6%
45.3%
21.7%
68.6%
8.8%
58.1%
35.9%
24.9%
83.6%
23.2%
67.2%
39.9%
21.8%
85.6%

1041
42.0%
62.7%
42.2%
23.1%
70.6%
19.1%
56.4%
32.9%
25.7%
84.8%
36.9%
67.8%
43.0%
26.2%
88.1%

1042
39.5%
63.0%
47.2%
32.8%
70.4%
21.6%
64.5%
31.0%
22.4%
85.7%
29.6%
67.8%
41.4%
29.8%
86.3%

1043
29.7%
58.9%
43.3%
25.6%
67.5%
6.7%
50.5%
35.0%
30.3%
84.3%
22.6%
66.2%
42.5%
23.2%
86.2%

1044
29.6%
62.0%
42.7%
32.8%
69.7%
6.5%
55.1%
30.1%
30.0%
86.2%
24.5%
68.5%
40.2%
32.0%
87.0%

1045
31.0%
60.2%
44.8%
25.6%
68.8%
13.0%
61.2%
35.6%
26.8%
85.5%
23.2%
66.7%
43.3%
27.7%
85.6%

1046
39.4%
58.7%
46.0%
33.5%
66.7%
16.6%
43.4%
23.5%
24.1%
82.3%
30.8%
62.6%
38.0%
27.0%
84.2%

1047
37.6%
60.1%
44.5%
37.1%
66.7%
8.6%
62.7%
27.6%
24.4%
85.3%
27.3%
64.9%
40.6%
33.0%
85.1%

1048
33.0%
62.3%
46.2%
30.9%
70.2%
9.9%
47.1%
37.0%
29.6%
84.7%
25.8%
64.9%
42.9%
28.6%
87.2%

1049
34.3%
69.3%
50.1%
42.8%
75.9%
8.8%
54.0%
36.3%
43.0%
86.6%
24.3%
68.2%
42.2%
39.0%
87.4%

1050
44.2%
65.1%
48.1%
35.9%
72.3%
27.0%
56.6%
26.6%
27.9%
87.4%
36.0%
68.5%
41.8%
30.3%
88.0%

1051
43.9%
69.1%
56.4%
50.5%
74.9%
6.9%
55.5%
19.0%
23.9%
87.0%
17.7%
72.0%
36.2%
35.3%
87.1%

1052
38.5%
64.7%
48.2%
32.9%
71.6%
12.2%
58.2%
41.0%
38.3%
87.0%
34.5%
72.1%
46.9%
31.5%
88.3%

1053
32.7%
61.4%
45.1%
36.8%
69.7%
5.8%
44.6%
24.2%
28.2%
85.6%
20.9%
65.6%
38.9%
33.7%
86.4%

1054
52.6%
78.8%
66.9%
52.8%
83.7%
5.7%
67.7%
39.6%
32.7%
92.1%
31.0%
77.4%
51.3%
32.9%
92.2%

1055
48.0%
67.5%
53.2%
39.0%
73.1%
27.3%
58.6%
35.6%
37.4%
88.6%
40.6%
73.5%
51.6%
33.9%
87.6%

1056
37.3%
62.9%
47.9%
41.0%
70.0%
7.9%
66.3%
27.5%
21.3%
87.2%
22.6%
69.6%
43.3%
36.2%
88.3%

1057
30.9%
62.8%
46.9%
33.4%
71.0%
7.9%
41.2%
28.4%
24.8%
87.4%
23.0%
66.5%
40.8%
22.6%
86.9%

1058
34.8%
67.0%
53.1%
45.6%
73.9%
6.0%
51.0%
23.3%
28.4%
88.5%
20.1%
71.3%
41.4%
31.2%
88.3%

1059
40.2%
69.1%
55.8%
42.4%
75.4%
4.6%
55.6%
32.5%
33.2%
87.2%
23.8%
69.9%
47.1%
30.0%
86.8%

1060
35.0%
57.3%
41.5%
28.2%
66.1%
16.5%
40.6%
22.8%
24.3%
83.8%
26.9%
61.2%
34.0%
25.0%
83.8%

1061
32.3%
62.0%
45.8%
37.5%
69.0%
7.4%
64.8%
33.2%
26.1%
86.0%
20.5%
67.3%
42.9%
33.7%
87.3%

1062
27.1%
61.7%
44.5%
31.1%
70.6%
6.6%
38.2%
27.9%
22.0%
87.4%
19.3%
66.7%
42.2%
21.6%
87.6%

1063
25.8%
64.7%
46.2%
40.6%
73.2%
5.3%
43.7%
21.2%
26.6%
87.5%
17.9%
68.4%
35.9%
31.2%
87.8%

1064
22.4%
60.4%
41.1%
28.5%
67.4%
9.7%
58.8%
31.8%
24.5%
85.4%
16.4%
64.9%
40.4%
26.5%
84.7%

1065
36.9%
60.4%
45.9%
31.9%
68.1%
24.1%
41.0%
22.3%
18.2%
85.5%
30.4%
64.7%
41.0%
21.4%
84.0%

1066
45.2%
74.9%
61.8%
55.1%
79.6%
10.3%
78.0%
39.5%
37.8%
91.6%
18.5%
80.2%
55.1%
49.2%
91.7%

1067
25.0%
62.8%
47.1%
32.2%
71.3%
7.1%
39.5%
26.3%
20.3%
85.1%
19.5%
65.1%
42.5%
25.1%
86.6%

1068
23.3%
63.3%
45.8%
37.2%
70.0%
4.3%
49.1%
23.7%
30.7%
88.4%
16.2%
69.8%
38.9%
29.2%
87.6%

1069
26.6%
68.8%
53.2%
35.6%
75.7%
9.1%
64.8%
26.8%
26.9%
89.8%
15.5%
71.9%
42.2%
34.9%
88.9%

1070
35.4%
63.3%
48.8%
34.0%
69.2%
28.3%
46.1%
24.9%
21.9%
85.4%
31.2%
67.3%
44.8%
26.7%
85.5%

1071
29.6%
66.4%
52.2%
44.4%
73.5%
13.1%
75.0%
30.5%
30.0%
90.7%
21.3%
70.6%
46.5%
38.8%
88.4%

1072
20.3%
56.9%
40.9%
27.7%
66.0%
6.3%
36.6%
24.2%
21.9%
82.6%
15.2%
59.9%
36.3%
21.6%
83.7%

1073
20.1%
59.3%
40.9%
34.4%
67.0%
6.1%
45.8%
22.3%
24.4%
85.8%
15.0%
67.7%
40.1%
31.0%
87.4%

1074
21.1%
60.3%
44.4%
29.6%
67.9%
8.5%
61.2%
36.3%
27.3%
86.5%
16.8%
67.6%
43.7%
27.6%
86.6%

1075
37.6%
64.0%
47.1%
32.0%
71.3%
22.8%
44.1%
24.0%
21.1%
86.3%
35.6%
69.7%
43.1%
26.2%
89.0%

1076
33.8%
65.2%
51.3%
44.5%
71.7%
6.4%
52.1%
16.0%
22.1%
85.5%
15.8%
70.2%
31.9%
30.1%
88.3%

1077
20.3%
60.4%
45.6%
31.9%
69.5%
7.9%
41.3%
29.1%
26.8%
83.7%
18.4%
61.4%
40.6%
26.4%
84.9%

1078
22.4%
59.4%
40.6%
33.8%
68.0%
6.1%
45.0%
20.7%
31.4%
86.2%
18.1%
66.1%
33.8%
33.3%
87.3%

1079
30.7%
66.4%
48.2%
42.1%
73.8%
8.6%
50.7%
21.3%
24.3%
83.8%
17.4%
64.1%
28.2%
26.4%
86.1%

1080
29.8%
63.1%
47.5%
33.8%
71.2%
7.0%
46.2%
32.9%
33.8%
87.9%
24.2%
68.5%
48.9%
33.3%
90.0%

1081
22.5%
62.5%
44.5%
38.0%
70.2%
8.9%
43.2%
34.0%
42.5%
88.3%
19.8%
67.2%
44.3%
43.0%
88.6%

1082
22.6%
61.7%
45.4%
33.7%
69.2%
5.6%
68.0%
47.8%
39.2%
87.3%
15.0%
72.1%
50.3%
35.8%
88.7%

1083
41.0%
62.2%
46.6%
34.5%
69.7%
16.2%
35.5%
20.2%
24.2%
87.0%
38.3%
62.4%
33.8%
29.3%
90.3%

1084
33.6%
59.9%
45.5%
37.6%
66.6%
5.6%
63.3%
25.6%
23.6%
84.0%
17.7%
70.3%
31.6%
26.5%
85.6%

1085
24.3%
58.5%
42.9%
28.5%
66.8%
6.8%
41.3%
30.7%
23.3%
85.1%
17.9%
61.6%
41.6%
23.9%
88.8%

1086
26.1%
63.6%
41.9%
36.1%
70.9%
4.7%
40.5%
26.8%
41.8%
88.3%
17.8%
64.0%
38.9%
46.6%
90.2%

1087
25.9%
64.7%
47.7%
32.2%
71.0%
7.0%
52.4%
26.3%
20.4%
86.3%
17.5%
64.5%
35.8%
29.4%
89.2%

1088
41.2%
62.0%
44.8%
30.3%
69.9%
31.7%
50.4%
26.5%
20.1%
87.5%
46.3%
66.5%
36.8%
26.2%
89.7%

1089
44.5%
66.3%
49.7%
43.9%
72.0%
6.5%
70.7%
19.0%
13.2%
87.7%
25.0%
78.1%
22.5%
18.4%
90.3%

1090
25.1%
58.4%
41.4%
24.8%
67.7%
5.8%
37.8%
33.5%
28.6%
86.9%
19.8%
59.9%
42.2%
26.4%
89.0%

1091
25.4%
63.6%
41.0%
33.9%
71.7%
5.7%
40.5%
19.7%
28.7%
84.9%
18.6%
59.9%
25.4%
30.4%
88.9%

1092
29.7%
61.0%
41.6%
27.1%
69.6%
5.9%
44.8%
24.7%
22.2%
85.0%
20.6%
63.0%
35.0%
26.9%
88.2%

1093
47.0%
64.3%
47.1%
29.4%
71.2%
34.4%
49.1%
26.3%
22.1%
92.0%
61.4%
70.9%
38.8%
25.4%
92.8%

1094
44.1%
66.2%
45.6%
38.5%
71.4%
7.4%
77.7%
31.4%
21.5%
91.9%
25.7%
79.1%
32.1%
23.5%
90.7%

1095
33.6%
64.3%
46.2%
22.3%
72.3%
5.1%
33.0%
27.8%
21.1%
89.9%
27.1%
65.1%
39.7%
17.9%
90.7%

1096
31.6%
64.0%
40.8%
35.1%
70.0%
5.2%
42.2%
21.2%
30.5%
86.0%
19.7%
64.0%
27.3%
33.3%
89.7%

1097
33.6%
64.1%
41.0%
24.6%
71.0%
8.4%
58.8%
33.4%
38.0%
89.2%
25.7%
70.3%
37.8%
34.7%
91.9%

1098
50.5%
68.0%
45.9%
26.5%
74.6%
37.2%
44.8%
25.8%
20.8%
88.3%
53.0%
68.1%
34.1%
22.3%
90.4%

1099
46.1%
67.3%
45.3%
38.6%
73.3%
10.7%
75.6%
36.7%
29.3%
89.7%
27.1%
78.2%
35.1%
25.1%
90.2%

1100
34.1%
63.1%
43.9%
21.0%
70.8%
24.5%
65.5%
57.2%
42.4%
89.9%
28.8%
68.1%
46.7%
24.8%
89.2%

1101
32.5%
65.0%
40.1%
34.7%
72.3%
4.7%
63.1%
25.1%
30.0%
90.2%
21.5%
74.1%
33.6%
34.1%
90.5%

1102
38.1%
66.1%
41.1%
24.1%
72.4%
6.2%
53.1%
35.9%
38.8%
90.4%
18.9%
63.9%
35.6%
31.7%
87.7%

1103
52.4%
68.4%
44.2%
28.1%
75.2%
43.7%
55.0%
28.5%
25.0%
89.0%
56.5%
69.4%
33.7%
25.4%
91.8%

1104
56.0%
72.7%
51.2%
44.7%
77.3%
6.9%
65.8%
22.5%
15.9%
84.4%
24.2%
75.0%
26.4%
19.1%
88.0%

1105
35.6%
66.7%
41.5%
37.5%
72.6%
5.4%
45.5%
21.3%
25.6%
86.8%
21.8%
68.5%
29.7%
29.8%
89.1%

1106
39.6%
66.7%
43.7%
28.5%
72.7%
6.1%
50.7%
26.7%
22.5%
87.5%
22.5%
64.9%
32.4%
22.1%
88.8%

1107
41.0%
61.0%
34.1%
24.1%
70.5%
15.3%
42.6%
24.1%
17.7%
87.3%
40.1%
65.7%
32.3%
22.2%
89.9%

1108
29.1%
63.9%
36.0%
29.4%
71.0%
9.5%
74.5%
60.2%
41.9%
90.0%
16.6%
75.0%
51.9%
31.6%
89.9%

1109
26.6%
60.3%
37.5%
20.4%
69.8%
6.4%
37.5%
25.4%
17.1%
87.5%
20.6%
64.7%
34.5%
18.3%
88.7%

1110
20.4%
61.8%
34.0%
31.5%
70.0%
5.2%
47.3%
18.9%
24.1%
87.0%
17.8%
66.9%
29.7%
30.4%
89.9%

1111
23.5%
61.9%
34.2%
24.5%
70.2%
6.4%
48.7%
25.3%
19.1%
87.6%
19.6%
64.2%
29.6%
22.5%
88.9%

1112
36.7%
65.0%
39.2%
28.3%
76.8%
11.9%
35.3%
18.8%
15.1%
86.0%
23.5%
49.4%
25.8%
18.2%
88.7%

1113
29.0%
65.3%
29.8%
25.1%
72.7%
6.9%
51.1%
20.4%
14.6%
83.9%
17.9%
64.4%
24.5%
16.0%
87.1%

1114
12.8%
62.5%
43.7%
12.9%
71.1%
5.5%
30.1%
18.3%
13.2%
84.3%
13.6%
45.6%
26.4%
13.4%
84.4%

1115
13.8%
69.4%
31.9%
25.5%
75.5%
6.2%
36.2%
16.2%
17.6%
84.6%
12.3%
54.9%
23.8%
21.1%
86.9%

1116
19.2%
77.3%
46.3%
17.1%
84.0%
4.8%
41.4%
16.4%
12.8%
88.7%
12.6%
50.8%
21.6%
13.5%
89.7%

1117
56.7%
68.5%
30.0%
29.3%
82.7%
11.8%
29.0%
14.8%
12.6%
89.6%
36.6%
46.3%
19.2%
14.2%
90.8%

1118
25.3%
65.1%
22.4%
23.1%
73.1%
6.5%
62.0%
15.1%
11.6%
85.6%
16.4%
59.5%
21.8%
15.0%
86.2%

1119
17.0%
57.0%
39.3%
19.8%
72.8%
6.3%
35.0%
20.4%
13.6%
85.9%
18.0%
50.5%
27.4%
16.8%
88.3%

1120
17.8%
60.0%
29.9%
32.6%
72.8%
7.1%
44.1%
19.0%
19.2%
85.7%
15.9%
55.2%
25.1%
21.7%
87.1%

1121
18.4%
74.0%
44.1%
34.8%
81.9%
5.0%
36.3%
16.5%
15.8%
89.2%
13.0%
45.5%
22.5%
18.0%
89.3%

1122
47.5%
61.0%
28.2%
25.7%
72.9%
14.4%
35.7%
17.2%
16.9%
86.7%
34.8%
52.3%
25.1%
18.5%
89.4%

1123
38.8%
72.6%
18.8%
18.5%
79.6%
5.9%
67.3%
14.3%
10.3%
87.3%
19.3%
68.1%
19.1%
12.1%
89.6%

1124
23.6%
58.9%
29.6%
14.0%
71.4%
7.0%
32.3%
19.4%
18.8%
87.5%
18.9%
50.3%
26.1%
15.6%
89.0%

1125
22.3%
64.6%
29.0%
40.5%
79.1%
5.4%
34.0%
15.6%
17.8%
88.0%
16.7%
47.5%
20.9%
18.8%
87.9%

1126
24.1%
72.2%
24.7%
24.0%
83.3%
6.3%
40.8%
13.8%
13.2%
89.3%
15.8%
50.3%
18.1%
12.0%
90.9%

1127
44.6%
57.3%
26.3%
20.9%
71.9%
21.7%
45.3%
20.7%
15.4%
84.8%
33.9%
54.3%
25.9%
16.0%
85.8%

1128
42.0%
70.9%
26.8%
25.8%
77.9%
11.3%
67.5%
18.2%
15.7%
87.0%
25.9%
73.2%
22.7%
16.8%
90.4%

1129
30.1%
54.7%
29.9%
16.2%
70.8%
7.8%
35.7%
23.1%
16.3%
86.5%
19.6%
51.9%
28.4%
17.3%
86.6%

1130
22.2%
60.1%
27.3%
29.5%
70.9%
6.8%
44.5%
18.8%
20.4%
85.3%
19.2%
57.7%
24.5%
21.1%
86.9%

1131
34.5%
59.8%
25.6%
19.4%
74.2%
8.7%
55.8%
19.4%
14.7%
87.6%
17.5%
53.8%
22.0%
15.6%
88.6%

1132
47.0%
60.7%
26.4%
19.9%
73.3%
18.4%
42.6%
18.5%
16.4%
88.0%
36.9%
58.1%
25.5%
18.0%
88.8%

1133
37.8%
63.0%
27.3%
20.0%
70.0%
9.9%
63.6%
21.5%
15.0%
85.5%
25.3%
67.8%
26.2%
18.7%
86.8%

1134
34.3%
57.2%
29.6%
15.4%
73.4%
11.5%
34.0%
18.2%
13.4%
84.1%
21.5%
51.1%
25.9%
15.0%
86.9%

1135
26.4%
56.4%
24.1%
20.3%
67.7%
7.1%
47.9%
20.6%
23.0%
85.2%
19.5%
56.5%
24.6%
18.6%
84.2%

1136
30.8%
54.4%
23.9%
16.1%
70.5%
8.3%
53.0%
21.5%
14.8%
85.9%
23.1%
56.2%
25.7%
16.7%
87.5%

1137
38.2%
60.6%
30.9%
18.6%
69.5%
23.6%
52.7%
29.2%
19.3%
82.1%
35.9%
62.5%
28.2%
18.7%
87.3%

1138
36.0%
62.0%
31.8%
23.9%
68.9%
9.9%
59.6%
25.0%
17.6%
83.6%
21.6%
68.6%
29.0%
19.8%
86.7%

1139
25.7%
53.8%
29.4%
14.0%
66.4%
10.6%
51.7%
27.2%
18.5%
84.7%
21.6%
56.7%
28.9%
16.5%
84.8%

1140
29.9%
62.9%
25.7%
19.1%
70.4%
6.2%
49.8%
19.1%
20.6%
84.6%
18.8%
64.6%
26.2%
20.4%
86.9%

1141
23.8%
58.5%
27.6%
15.2%
67.1%
10.8%
52.1%
19.8%
14.0%
84.0%
20.0%
60.3%
25.5%
16.9%
84.8%

1142
42.8%
63.0%
42.0%
19.3%
70.5%
16.6%
44.1%
22.2%
16.7%
85.1%
34.0%
64.5%
31.9%
19.2%
86.5%

1143
39.2%
66.2%
35.6%
22.7%
72.6%
10.1%
62.3%
23.9%
16.5%
85.2%
24.4%
69.4%
29.6%
19.3%
88.1%

1144
26.1%
57.6%
35.2%
16.3%
66.2%
8.2%
47.3%
29.4%
18.9%
81.8%
21.5%
59.9%
32.6%
17.5%
84.7%

1145
26.9%
59.6%
29.3%
21.0%
68.1%
6.3%
50.6%
23.0%
22.8%
84.7%
19.6%
63.6%
29.9%
22.0%
85.4%

1146
28.0%
61.1%
31.3%
14.8%
68.3%
9.9%
62.8%
33.9%
19.2%
85.8%
20.0%
63.7%
28.6%
17.2%
85.7%

1147
43.2%
62.3%
39.9%
18.7%
70.2%
18.7%
44.6%
22.4%
15.6%
84.1%
35.7%
62.6%
31.6%
17.8%
86.1%

1148
30.0%
57.6%
34.9%
21.2%
65.5%
7.6%
55.9%
22.9%
18.2%
82.7%
23.8%
64.4%
31.0%
20.2%
85.9%

1149
28.3%
59.6%
39.1%
16.5%
69.3%
7.6%
47.6%
31.1%
23.0%
82.9%
21.5%
64.2%
40.0%
18.5%
86.9%

1150
25.0%
57.3%
31.7%
21.4%
64.7%
6.5%
47.7%
23.3%
26.0%
81.5%
17.6%
60.8%
29.1%
21.9%
81.0%

1151
28.3%
59.9%
42.2%
18.6%
68.5%
5.9%
57.0%
30.7%
27.7%
84.9%
19.0%
66.7%
36.5%
20.5%
87.8%

1152
35.4%
60.8%
41.2%
19.6%
68.7%
15.0%
46.3%
23.4%
17.8%
84.1%
31.2%
66.5%
35.1%
19.4%
87.2%

1153
35.9%
60.4%
44.9%
29.0%
67.8%
7.7%
59.8%
26.2%
17.9%
83.0%
25.0%
66.3%
36.1%
22.7%
85.5%

1154
26.4%
58.5%
41.4%
24.9%
67.3%
6.3%
39.2%
25.4%
26.8%
84.6%
18.4%
65.8%
42.0%
24.3%
86.2%

1155
21.3%
57.7%
38.3%
26.2%
66.1%
6.8%
48.3%
24.0%
26.1%
83.4%
17.4%
62.4%
37.4%
27.5%
84.0%

1156
26.2%
59.9%
37.5%
17.4%
68.1%
8.8%
60.0%
30.7%
21.8%
85.8%
21.7%
67.1%
35.8%
20.1%
86.3%

1157
38.9%
60.6%
42.0%
22.7%
68.7%
19.5%
50.8%
27.7%
24.8%
81.7%
30.6%
64.4%
38.5%
22.7%
83.1%

1158
35.3%
61.4%
45.6%
31.1%
68.7%
6.7%
60.7%
30.3%
25.8%
83.7%
21.0%
67.5%
41.7%
29.3%
85.5%

1159
25.2%
58.6%
39.9%
24.4%
67.4%
6.6%
46.1%
30.3%
26.9%
84.7%
22.3%
65.6%
41.6%
23.4%
86.5%

1160
27.2%
57.3%
40.9%
31.7%
65.9%
6.5%
45.2%
22.8%
24.4%
84.2%
17.9%
65.6%
39.8%
31.2%
85.4%

1161
28.4%
60.2%
43.3%
28.2%
67.5%
6.1%
61.7%
36.6%
31.6%
86.3%
18.4%
66.7%
42.3%
27.6%
85.9%

1162
37.7%
61.7%
45.1%
30.2%
69.4%
12.7%
40.1%
22.1%
26.2%
85.6%
28.4%
63.9%
38.4%
26.5%
88.2%

1163
39.3%
66.6%
53.8%
47.5%
72.7%
7.9%
67.0%
22.4%
19.1%
85.9%
27.5%
68.5%
42.4%
34.8%
86.1%

1164
27.0%
59.4%
42.0%
27.1%
68.2%
7.6%
42.9%
26.3%
24.0%
85.0%
21.2%
64.2%
38.2%
21.0%
86.6%

1165
22.1%
56.8%
39.6%
31.4%
65.9%
6.3%
45.3%
25.7%
26.5%
84.3%
16.9%
61.2%
34.8%
29.2%
83.8%

1166
31.9%
67.5%
51.4%
36.9%
73.6%
7.0%
61.9%
30.7%
25.4%
87.7%
20.8%
69.3%
46.1%
30.4%
87.2%

1167
37.8%
61.2%
44.6%
34.1%
69.2%
13.5%
41.0%
22.0%
21.1%
86.4%
30.6%
68.1%
42.7%
29.5%
88.0%

1168
48.3%
70.2%
57.8%
53.4%
76.3%
6.1%
72.5%
26.6%
22.3%
88.7%
26.0%
72.7%
51.2%
42.9%
87.7%

1169
28.1%
60.8%
45.4%
33.6%
68.6%
6.4%
43.2%
28.1%
23.9%
86.5%
20.3%
66.2%
43.5%
23.6%
85.9%

1170
33.1%
64.8%
48.8%
42.7%
71.6%
4.8%
44.0%
20.1%
25.2%
88.1%
21.2%
69.0%
41.2%
34.8%
87.3%

1171
33.0%
63.6%
47.4%
33.3%
70.3%
8.8%
66.0%
35.6%
24.9%
86.4%
24.6%
69.1%
41.2%
24.3%
86.9%

1172
38.1%
63.1%
47.1%
37.0%
70.4%
13.5%
42.2%
22.3%
19.4%
86.2%
30.6%
68.0%
41.9%
28.8%
87.1%

1173
34.6%
61.1%
45.7%
38.4%
68.8%
7.9%
64.1%
23.4%
17.7%
86.9%
23.1%
70.2%
43.8%
35.9%
88.6%

1174
22.0%
55.7%
38.8%
27.9%
65.5%
6.1%
37.5%
24.5%
20.1%
85.1%
20.6%
62.2%
35.6%
20.5%
85.1%

1175
24.6%
61.7%
43.9%
36.3%
68.6%
5.1%
38.1%
21.3%
25.8%
86.8%
15.9%
64.8%
37.4%
31.5%
84.9%

1176
22.7%
59.7%
44.9%
33.8%
68.5%
5.9%
54.5%
25.9%
22.3%
85.4%
16.7%
63.2%
37.7%
26.4%
85.8%

1177
34.3%
60.6%
43.5%
31.2%
68.8%
12.5%
41.1%
21.4%
19.9%
85.6%
23.9%
66.1%
42.9%
27.5%
87.7%

1178
29.9%
58.5%
41.9%
35.5%
66.3%
12.0%
60.4%
25.2%
19.6%
84.3%
20.8%
65.5%
40.7%
31.0%
85.4%

1179
23.5%
61.2%
44.9%
28.9%
69.2%
5.6%
41.6%
28.5%
26.0%
87.2%
16.5%
68.1%
44.6%
22.6%
86.3%

1180
20.0%
59.1%
41.9%
34.2%
67.1%
5.3%
43.6%
19.2%
23.9%
83.8%
14.4%
63.5%
34.1%
26.3%
82.9%

1181
27.2%
66.5%
51.4%
35.9%
73.3%
5.2%
51.4%
26.7%
28.8%
86.7%
15.5%
69.4%
44.5%
28.3%
87.4%

1182
36.1%
61.3%
45.8%
32.4%
68.6%
19.2%
41.4%
21.8%
17.1%
84.8%
26.2%
66.2%
41.2%
21.7%
86.1%

1183
40.6%
74.2%
61.5%
55.5%
79.2%
7.4%
68.5%
19.8%
15.4%
88.3%
16.3%
75.4%
46.5%
35.7%
90.1%

1184
21.2%
67.3%
52.8%
33.9%
73.8%
6.1%
35.3%
23.4%
17.3%
85.2%
14.0%
68.5%
43.6%
21.8%
86.6%

1185
25.8%
68.6%
50.1%
45.7%
75.4%
4.6%
36.8%
22.2%
36.8%
88.3%
12.9%
70.4%
39.3%
40.8%
90.0%

1186
32.9%
61.6%
46.0%
31.1%
69.3%
15.2%
42.2%
20.4%
20.8%
86.2%
23.6%
67.2%
42.2%
22.6%
86.7%

1187
24.8%
60.6%
45.0%
38.7%
68.7%
6.9%
58.3%
20.9%
17.5%
85.1%
17.7%
67.2%
40.5%
30.1%
87.8%

1188
19.0%
61.3%
43.5%
29.5%
69.2%
6.6%
52.8%
38.3%
26.9%
87.4%
15.2%
65.6%
44.2%
26.2%
87.1%

1189
18.9%
56.3%
38.2%
31.5%
66.1%
5.6%
38.1%
17.8%
19.8%
83.4%
15.0%
61.1%
35.9%
29.5%
83.9%

1190
20.8%
64.9%
49.5%
33.8%
71.8%
6.0%
48.0%
22.5%
19.6%
86.7%
14.9%
67.8%
43.3%
24.1%
86.8%

1191
31.9%
63.2%
46.6%
30.8%
71.2%
11.3%
41.6%
25.0%
26.6%
86.7%
25.1%
71.2%
47.3%
29.3%
90.3%

1192
31.9%
64.1%
49.1%
40.9%
70.8%
7.1%
65.5%
29.6%
17.4%
85.7%
16.9%
74.7%
44.1%
29.0%
89.4%

1193
20.1%
68.8%
56.4%
41.3%
74.9%
4.1%
22.8%
18.3%
13.2%
89.2%
11.7%
71.1%
56.7%
18.5%
91.5%

1194
18.6%
60.3%
40.5%
32.3%
68.5%
5.8%
35.1%
17.8%
21.1%
84.4%
13.7%
64.2%
33.1%
27.3%
86.9%

1195
20.1%
62.0%
45.1%
33.1%
70.1%
5.4%
40.6%
19.8%
16.9%
86.3%
14.4%
68.1%
38.6%
27.9%
89.0%

1196
40.9%
70.9%
54.0%
40.4%
77.3%
16.6%
35.5%
18.9%
27.3%
91.5%
33.8%
70.1%
45.0%
35.4%
93.4%

1197
35.1%
64.1%
48.1%
41.0%
70.2%
6.0%
60.4%
19.8%
21.5%
86.5%
17.4%
74.7%
33.3%
32.6%
89.8%

1198
17.6%
63.0%
47.3%
30.3%
70.6%
5.1%
29.5%
23.2%
19.8%
86.5%
13.0%
65.9%
45.1%
19.0%
88.7%

1199
19.8%
63.3%
44.4%
37.6%
71.2%
6.6%
42.0%
18.8%
28.1%
87.4%
15.9%
67.4%
37.8%
37.8%
90.4%

1200
18.1%
63.6%
47.4%
30.7%
71.2%
5.0%
51.5%
26.5%
25.1%
87.8%
13.7%
71.0%
43.5%
27.8%
88.9%

1201
37.3%
59.6%
40.2%
30.1%
69.0%
11.8%
36.4%
19.5%
21.4%
87.7%
35.2%
61.9%
34.2%
29.4%
89.8%

1202
30.5%
60.5%
44.0%
36.8%
68.3%
6.0%
56.9%
19.6%
16.7%
83.3%
18.2%
69.2%
27.0%
24.7%
87.9%

1203
21.2%
62.6%
44.8%
25.9%
70.5%
5.1%
33.0%
22.6%
17.1%
85.7%
16.5%
60.9%
36.0%
17.1%
88.1%

1204
20.0%
61.0%
39.5%
32.5%
68.5%
5.3%
38.5%
18.1%
24.7%
84.8%
14.3%
60.9%
27.6%
31.1%
87.8%

1205
23.1%
65.2%
47.9%
34.8%
72.7%
7.1%
45.6%
20.9%
17.4%
88.0%
14.8%
62.3%
34.8%
28.1%
90.8%

1206
43.2%
61.8%
43.8%
32.0%
68.7%
13.8%
34.1%
16.7%
16.2%
86.9%
42.1%
59.6%
27.4%
22.3%
87.5%

1207
33.7%
57.2%
39.0%
28.9%
67.8%
10.9%
60.6%
24.9%
15.8%
84.3%
24.5%
64.7%
27.8%
17.7%
85.2%

1208
24.2%
61.8%
42.2%
25.5%
69.8%
4.6%
29.0%
20.4%
31.1%
89.0%
17.0%
59.1%
37.9%
27.6%
89.9%

1209
21.8%
59.4%
37.9%
31.6%
66.8%
5.2%
33.9%
15.3%
25.0%
86.3%
15.2%
56.1%
26.7%
33.7%
86.5%

1210
22.8%
62.6%
43.5%
27.7%
69.6%
6.2%
43.9%
19.4%
15.1%
88.2%
14.9%
60.2%
26.2%
19.9%
89.6%

1211
59.7%
74.1%
50.0%
28.8%
79.5%
16.6%
28.9%
13.9%
12.0%
89.5%
57.0%
60.8%
23.0%
16.2%
93.2%

1212
48.3%
73.8%
56.4%
46.2%
79.0%
4.7%
70.1%
15.5%
16.7%
90.4%
25.9%
80.0%
23.0%
19.3%
92.3%

1213
30.8%
63.7%
46.5%
22.3%
70.6%
4.5%
25.6%
17.5%
17.4%
85.4%
23.2%
59.1%
33.0%
15.6%
87.9%

1214
22.3%
65.8%
40.7%
34.9%
72.7%
4.7%
39.0%
18.8%
24.1%
85.4%
14.6%
59.2%
24.5%
29.0%
88.5%

1215
34.9%
69.6%
45.5%
26.8%
75.7%
3.4%
41.3%
19.8%
20.3%
93.0%
16.3%
61.8%
26.6%
22.1%
93.1%

1216
46.2%
65.2%
41.9%
27.1%
72.7%
15.1%
36.4%
19.1%
16.7%
88.5%
46.6%
65.6%
29.8%
19.7%
89.6%

1217
43.1%
65.0%
45.0%
37.8%
72.2%
7.0%
65.9%
20.3%
15.5%
87.8%
20.8%
73.2%
28.5%
21.3%
88.6%

1218
29.7%
61.0%
42.0%
19.9%
69.1%
6.1%
40.4%
28.7%
31.4%
87.7%
26.9%
66.5%
35.3%
23.5%
88.3%

1219
26.2%
60.6%
35.9%
30.1%
69.3%
5.3%
42.2%
19.2%
24.4%
86.9%
20.6%
64.8%
27.5%
29.6%
87.9%

1220
33.9%
63.1%
40.7%
25.4%
70.9%
5.7%
43.5%
19.9%
18.6%
85.9%
20.7%
61.1%
28.4%
20.6%
86.0%

1221
44.8%
65.3%
41.3%
26.9%
73.4%
15.9%
43.3%
25.0%
32.0%
87.6%
42.4%
68.0%
37.8%
27.5%
89.5%

1222
40.1%
67.6%
47.2%
37.9%
74.3%
7.9%
71.2%
55.8%
33.8%
88.5%
21.0%
73.9%
51.7%
29.5%
89.9%

1223
28.2%
63.3%
43.6%
21.1%
70.3%
6.8%
35.8%
24.7%
21.5%
85.3%
22.0%
66.9%
39.2%
20.0%
88.5%

1224
26.3%
62.7%
37.2%
32.5%
70.6%
4.9%
47.4%
21.0%
40.0%
88.5%
17.7%
68.5%
27.2%
35.3%
90.9%

1225
36.0%
64.9%
43.3%
24.2%
71.7%
9.0%
65.1%
34.3%
21.6%
88.2%
27.9%
69.1%
33.7%
19.7%
88.9%

1226
38.9%
61.5%
33.9%
25.6%
71.0%
15.2%
37.4%
19.4%
15.8%
86.2%
33.4%
61.6%
28.7%
21.0%
88.3%

1227
23.1%
64.0%
33.3%
29.1%
71.1%
9.3%
68.8%
26.5%
18.8%
88.0%
17.8%
72.5%
29.4%
23.4%
90.4%

1228
22.5%
59.8%
36.8%
19.7%
70.8%
7.0%
45.3%
34.6%
22.8%
87.5%
18.4%
63.3%
39.2%
18.6%
88.6%

1229
16.3%
59.3%
30.4%
29.8%
69.2%
5.4%
41.9%
15.4%
19.5%
86.8%
13.5%
64.9%
28.7%
28.0%
88.1%

1230
15.3%
62.7%
34.8%
24.5%
72.3%
5.6%
53.9%
24.3%
18.0%
88.0%
12.6%
61.0%
27.2%
21.2%
89.2%

1231
50.1%
63.5%
27.4%
24.8%
76.5%
12.5%
25.9%
13.8%
10.0%
85.3%
28.7%
41.0%
18.0%
12.8%
86.2%

1232
26.9%
68.6%
24.9%
26.9%
76.6%
6.6%
60.1%
15.6%
11.4%
85.8%
16.6%
67.3%
21.2%
15.8%
89.0%

1233
19.8%
68.7%
48.3%
22.0%
79.2%
6.0%
44.4%
25.5%
13.1%
87.4%
16.8%
51.0%
27.7%
15.6%
88.6%

1234
12.2%
66.0%
37.0%
38.8%
76.4%
5.9%
62.3%
24.2%
21.6%
88.0%
11.2%
65.3%
23.6%
21.2%
89.5%

1235
12.5%
66.3%
50.6%
36.9%
77.4%
6.0%
34.0%
16.4%
13.6%
82.5%
12.4%
47.1%
25.8%
18.3%
86.0%

1236
54.0%
66.1%
25.3%
25.9%
78.7%
17.2%
29.1%
13.0%
10.5%
87.2%
37.9%
47.0%
19.4%
14.4%
90.1%

1237
31.4%
74.1%
22.4%
23.3%
81.1%
6.6%
65.5%
14.5%
10.6%
87.4%
17.1%
68.3%
18.5%
12.4%
90.9%

1238
16.0%
59.0%
33.8%
17.6%
72.1%
7.1%
33.5%
18.1%
14.6%
83.8%
14.6%
51.1%
25.1%
15.5%
87.1%

1239
12.8%
61.4%
30.7%
40.0%
74.1%
5.0%
38.5%
19.5%
20.7%
85.6%
12.1%
48.3%
22.7%
21.9%
86.6%

1240
41.7%
61.6%
26.9%
24.1%
73.2%
17.7%
32.5%
15.7%
12.1%
85.6%
27.0%
48.7%
21.4%
14.1%
84.3%

1241
27.8%
63.0%
21.2%
22.9%
73.5%
6.5%
63.0%
15.8%
12.1%
87.3%
18.8%
69.1%
21.8%
15.7%
89.1%

1242
24.5%
48.9%
26.4%
14.7%
69.4%
9.8%
46.5%
28.8%
21.8%
84.4%
19.5%
51.3%
28.2%
16.4%
87.5%

1243
20.8%
46.2%
20.6%
21.8%
71.6%
5.7%
64.8%
24.0%
16.8%
85.6%
18.7%
59.4%
24.7%
17.8%
87.2%

1244
36.1%
55.3%
23.7%
18.6%
68.5%
6.8%
38.3%
19.1%
14.5%
82.2%
22.7%
50.6%
23.3%
16.6%
84.5%

1245
31.2%
57.3%
24.2%
17.7%
66.7%
8.1%
56.1%
17.8%
14.0%
82.8%
22.8%
61.4%
25.0%
16.7%
85.3%

1246
33.2%
59.6%
29.9%
14.8%
72.1%
6.9%
34.6%
21.3%
14.8%
84.5%
20.3%
53.7%
27.3%
15.6%
86.8%

1247
33.6%
60.0%
24.5%
25.4%
72.3%
5.8%
48.1%
16.1%
14.4%
87.1%
24.9%
57.2%
22.1%
20.5%
88.2%

1248
33.3%
59.1%
25.3%
15.2%
68.8%
9.6%
57.0%
29.7%
17.3%
82.4%
22.4%
60.8%
26.6%
16.9%
85.0%

1249
49.9%
66.9%
28.6%
20.3%
75.2%
35.4%
41.6%
15.1%
11.9%
86.1%
42.2%
51.8%
22.5%
15.4%
88.4%

1250
35.6%
63.2%
31.7%
21.0%
70.1%
12.4%
62.4%
22.5%
17.7%
85.2%
23.5%
67.0%
24.5%
18.0%
86.0%

1251
22.1%
58.4%
33.2%
15.2%
68.0%
7.1%
47.6%
29.0%
18.3%
84.2%
18.1%
60.8%
30.9%
17.3%
85.5%

1252
19.1%
66.2%
29.6%
30.4%
74.1%
8.4%
56.2%
16.9%
19.1%
85.2%
14.6%
60.7%
23.2%
21.9%
88.1%

1253
16.0%
58.3%
25.2%
15.2%
66.9%
11.8%
54.8%
21.1%
14.7%
82.8%
18.8%
63.1%
26.2%
17.4%
85.2%

1254
37.8%
58.9%
32.8%
17.5%
67.3%
16.1%
47.0%
23.0%
15.9%
83.7%
35.3%
63.6%
29.1%
18.2%
85.7%

1255
34.0%
57.7%
36.2%
17.9%
65.7%
10.1%
60.8%
20.3%
14.1%
83.3%
25.0%
64.2%
29.3%
18.4%
86.1%

1256
14.7%
60.0%
32.7%
14.5%
68.6%
5.9%
56.2%
36.2%
21.7%
84.6%
15.3%
62.7%
32.4%
16.4%
86.0%

1257
20.5%
62.8%
26.8%
20.9%
70.7%
5.2%
58.2%
33.1%
25.4%
84.9%
16.1%
64.8%
29.4%
22.5%
87.5%

1258
34.3%
60.9%
30.0%
17.5%
69.5%
6.9%
52.9%
28.5%
18.1%
84.5%
20.5%
59.8%
28.0%
18.0%
85.3%

1259
35.6%
57.2%
31.9%
17.7%
66.8%
14.9%
45.7%
21.0%
14.9%
83.8%
31.5%
62.7%
29.5%
17.1%
86.3%

1260
20.1%
58.9%
39.5%
19.2%
67.1%
8.4%
59.3%
26.1%
19.8%
83.9%
18.1%
65.4%
34.1%
20.8%
85.8%

1261
29.9%
57.0%
37.3%
15.6%
65.0%
6.2%
41.4%
27.7%
21.3%
82.5%
21.4%
64.5%
38.9%
19.2%
85.4%

1262
22.2%
59.3%
30.8%
21.0%
67.3%
7.0%
54.9%
22.0%
18.5%
83.3%
18.7%
65.5%
28.8%
19.9%
86.0%

1263
21.4%
60.4%
40.0%
18.5%
68.5%
6.9%
51.9%
22.2%
15.6%
83.1%
19.5%
64.0%
36.8%
19.2%
85.3%

1264
29.3%
57.6%
36.9%
18.1%
66.8%
12.0%
49.6%
26.0%
26.3%
84.4%
26.1%
63.4%
34.7%
21.9%
86.7%

1265
24.6%
64.1%
47.1%
32.3%
71.6%
8.1%
63.6%
45.9%
31.0%
86.1%
20.7%
70.8%
45.9%
29.6%
89.1%

1266
16.8%
62.5%
38.3%
15.3%
70.9%
6.4%
44.7%
26.8%
19.3%
85.1%
16.1%
64.6%
36.3%
16.6%
87.2%

1267
14.8%
54.1%
30.7%
21.5%
63.2%
6.9%
43.8%
18.9%
18.8%
82.1%
13.8%
59.0%
29.9%
22.7%
82.8%

1268
23.3%
62.8%
40.1%
17.8%
71.1%
6.0%
49.6%
20.8%
18.8%
84.5%
16.2%
63.9%
33.1%
18.0%
86.5%

1269
36.9%
64.2%
49.5%
30.6%
72.0%
14.7%
42.0%
21.2%
19.3%
85.7%
27.4%
66.9%
43.7%
25.8%
86.7%

1270
37.0%
59.8%
43.7%
34.0%
67.3%
9.2%
58.5%
22.6%
18.1%
83.1%
27.2%
65.6%
40.2%
29.5%
86.9%

1271
12.4%
57.6%
39.3%
21.1%
66.6%
5.6%
53.0%
35.6%
22.9%
85.4%
14.4%
62.6%
37.3%
21.5%
85.1%

1272
18.6%
58.6%
30.1%
21.8%
67.3%
7.1%
51.9%
23.8%
24.3%
85.0%
15.4%
65.4%
32.9%
26.7%
87.3%

1273
43.9%
71.4%
48.5%
33.9%
77.9%
16.8%
46.8%
20.7%
16.1%
87.0%
33.0%
70.3%
38.7%
27.7%
90.1%

1274
31.5%
61.3%
44.1%
39.6%
68.0%
5.9%
58.8%
20.6%
15.6%
83.3%
21.1%
63.8%
39.6%
33.9%
83.9%

1275
24.4%
57.7%
41.1%
25.7%
67.1%
7.3%
40.1%
23.7%
16.1%
83.7%
20.4%
62.5%
35.7%
19.8%
85.6%

1276
20.7%
61.6%
43.7%
36.5%
69.8%
5.9%
46.1%
23.3%
24.3%
84.6%
15.8%
63.3%
39.6%
32.8%
86.0%

1277
26.6%
59.3%
44.6%
31.7%
67.7%
6.3%
57.3%
33.4%
29.5%
85.7%
16.4%
64.7%
41.2%
25.0%
84.7%

1278
35.2%
68.1%
53.6%
41.8%
74.7%
20.4%
41.5%
17.8%
15.8%
88.8%
28.3%
72.6%
47.2%
30.8%
89.6%

1279
22.0%
62.1%
47.0%
38.6%
69.6%
8.7%
69.9%
49.2%
29.6%
88.0%
19.2%
71.4%
47.3%
35.9%
88.7%

1280
14.8%
61.0%
43.2%
37.9%
70.1%
5.8%
43.0%
20.1%
22.6%
86.8%
15.1%
65.8%
35.6%
31.8%
88.4%

1281
15.5%
62.5%
44.8%
31.0%
69.8%
5.2%
46.9%
17.3%
13.7%
88.7%
13.3%
67.2%
41.1%
27.5%
87.8%

1282
30.2%
60.8%
45.4%
35.4%
69.7%
16.4%
40.3%
20.9%
18.0%
86.2%
26.1%
66.4%
43.0%
30.4%
88.3%

1283
31.4%
60.9%
46.0%
37.9%
68.3%
9.5%
62.3%
28.6%
22.1%
86.7%
20.0%
66.1%
41.3%
32.4%
86.1%

1284
17.5%
58.8%
43.4%
32.4%
68.7%
6.6%
44.4%
31.3%
23.2%
87.9%
15.6%
63.6%
38.2%
25.9%
85.8%

1285
13.1%
60.3%
39.4%
34.4%
68.2%
5.1%
43.7%
17.8%
19.2%
85.0%
13.3%
65.9%
34.9%
27.8%
85.7%

1286
15.0%
62.1%
44.0%
32.8%
69.8%
6.2%
47.4%
21.6%
26.3%
86.0%
15.0%
65.1%
38.0%
27.6%
85.5%

1287
34.6%
61.3%
45.4%
34.3%
68.8%
12.9%
38.9%
19.6%
16.1%
83.9%
25.9%
64.7%
36.9%
23.4%
85.9%

1288
20.4%
63.7%
48.8%
44.0%
70.0%
6.1%
62.3%
18.7%
14.7%
85.9%
13.3%
71.6%
46.9%
40.2%
88.5%

1289
14.6%
63.0%
43.7%
31.1%
70.7%
5.9%
32.4%
20.0%
16.4%
85.1%
12.6%
68.2%
40.6%
23.2%
87.5%

1290
20.8%
60.9%
43.3%
36.2%
68.2%
6.1%
56.5%
24.0%
24.1%
85.9%
15.2%
65.6%
38.3%
31.7%
85.9%

1291
13.9%
65.9%
48.9%
34.0%
72.6%
6.6%
43.5%
17.9%
16.2%
85.8%
13.5%
67.1%
41.3%
25.3%
87.4%

1292
31.1%
62.1%
46.0%
33.2%
70.7%
16.7%
38.5%
18.7%
14.9%
85.2%
29.7%
68.5%
40.2%
25.8%
88.5%

1293
15.1%
70.9%
58.4%
53.0%
76.5%
4.8%
62.3%
17.1%
12.1%
86.5%
10.6%
73.4%
50.1%
41.9%
88.6%

1294
19.4%
72.9%
58.5%
39.3%
78.5%
7.0%
52.2%
33.5%
22.6%
91.5%
13.2%
74.7%
55.5%
27.5%
90.7%

1295
11.7%
62.2%
41.6%
36.3%
68.8%
5.2%
40.9%
15.9%
20.3%
85.4%
11.4%
65.8%
33.8%
29.8%
84.8%

1296
17.6%
69.4%
54.6%
41.1%
75.2%
6.4%
35.8%
18.1%
14.8%
84.2%
13.7%
59.2%
30.5%
21.8%
87.6%

1297
23.7%
60.8%
43.8%
29.0%
69.0%
13.7%
40.8%
19.9%
17.3%
85.6%
21.6%
65.5%
40.2%
25.5%
88.0%

1298
18.0%
61.9%
49.2%
42.5%
69.0%
7.1%
62.6%
18.0%
13.7%
84.9%
13.5%
68.2%
45.3%
35.6%
87.1%

1299
18.6%
59.3%
43.5%
31.8%
67.1%
4.9%
29.3%
19.7%
17.0%
83.1%
13.5%
62.9%
42.0%
23.8%
83.4%

1300
12.5%
59.7%
41.0%
35.1%
68.3%
4.6%
41.0%
17.3%
19.3%
87.1%
13.8%
67.2%
37.5%
30.5%
86.6%

1301
16.7%
60.6%
44.4%
33.2%
68.4%
5.1%
44.4%
20.6%
16.8%
88.0%
12.8%
67.9%
44.3%
28.4%
87.8%

1302
25.5%
61.6%
44.9%
32.5%
68.6%
13.6%
44.8%
21.0%
18.2%
86.4%
25.3%
67.1%
41.8%
25.7%
87.2%

1303
21.4%
63.5%
48.8%
42.4%
70.5%
5.9%
56.8%
16.9%
12.5%
85.2%
13.0%
69.6%
42.3%
34.2%
87.1%

1304
14.6%
58.8%
42.9%
30.8%
67.4%
6.3%
44.7%
31.6%
30.1%
88.1%
14.9%
66.8%
44.5%
27.5%
89.2%

1305
14.9%
59.5%
41.3%
34.0%
69.0%
5.0%
37.8%
17.2%
21.6%
85.7%
11.5%
66.7%
39.7%
37.4%
88.3%

1306
14.2%
60.3%
39.9%
29.0%
68.0%
6.3%
35.2%
17.0%
17.8%
85.2%
12.6%
64.1%
31.7%
23.3%
86.7%

1307
29.0%
62.7%
47.1%
33.8%
71.8%
11.6%
36.9%
19.4%
18.2%
85.1%
21.8%
67.9%
44.8%
28.8%
89.0%

1308
17.3%
61.1%
45.8%
39.8%
68.2%
7.0%
58.6%
18.5%
15.6%
84.7%
12.5%
70.9%
33.2%
31.9%
88.0%

1309
14.2%
61.0%
40.9%
29.6%
69.5%
5.5%
34.5%
23.2%
17.2%
87.4%
12.9%
65.7%
45.1%
26.2%
89.1%

1310
17.6%
58.8%
43.2%
37.4%
67.5%
4.8%
32.7%
15.7%
19.5%
84.4%
12.5%
68.0%
40.4%
37.7%
88.0%

1311
13.9%
61.9%
40.2%
30.3%
69.7%
4.7%
42.0%
21.6%
15.6%
85.3%
11.9%
64.5%
31.8%
23.6%
88.0%

1312
32.6%
65.4%
46.7%
35.8%
71.7%
13.3%
35.4%
17.3%
14.2%
88.2%
34.8%
60.2%
28.3%
25.3%
92.1%

1313
25.2%
58.1%
39.0%
36.1%
65.6%
6.0%
63.4%
17.5%
14.3%
85.1%
15.9%
69.5%
28.0%
24.8%
87.1%

1314
14.7%
61.4%
41.1%
26.8%
70.0%
4.8%
41.7%
36.6%
27.7%
88.3%
13.8%
60.9%
44.9%
25.5%
89.9%

1315
14.3%
57.0%
35.7%
31.4%
66.1%
5.5%
38.0%
16.5%
20.2%
85.1%
13.2%
61.2%
28.3%
30.2%
87.5%

1316
23.5%
67.3%
50.2%
36.0%
73.9%
6.4%
49.2%
22.0%
16.2%
88.5%
18.6%
64.6%
30.6%
21.7%
90.8%

1317
37.7%
64.1%
41.7%
29.9%
72.4%
15.5%
39.6%
20.2%
18.3%
87.9%
37.1%
61.1%
28.2%
23.0%
89.1%

1318
28.1%
63.9%
46.9%
40.2%
71.0%
7.5%
67.0%
27.7%
18.4%
88.0%
19.1%
73.2%
36.6%
29.7%
89.7%

1319
22.8%
61.4%
42.3%
24.4%
68.9%
5.2%
32.4%
20.7%
15.9%
84.9%
21.1%
58.7%
31.4%
17.0%
89.0%

1320
14.4%
56.9%
36.4%
32.5%
65.7%
6.3%
35.2%
14.6%
15.3%
82.8%
11.9%
59.2%
25.0%
26.9%
87.9%

1321
16.2%
60.8%
36.3%
24.0%
68.3%
6.3%
42.1%
18.5%
13.8%
84.4%
14.7%
58.5%
25.3%
20.3%
85.9%

1322
40.4%
64.5%
40.6%
28.4%
71.5%
14.7%
38.3%
19.9%
27.2%
89.8%
33.9%
58.0%
28.3%
26.9%
91.3%

1323
39.7%
67.6%
43.7%
39.6%
73.5%
5.6%
54.3%
16.9%
12.8%
83.2%
16.1%
65.2%
22.9%
16.3%
85.2%

1324
34.2%
70.3%
49.5%
26.7%
76.7%
5.3%
37.0%
30.4%
15.1%
88.6%
32.3%
57.6%
35.1%
14.4%
91.4%

1325
13.5%
60.2%
31.7%
30.2%
68.0%
4.1%
41.8%
15.2%
25.0%
89.4%
11.2%
67.8%
25.0%
27.8%
89.3%

1326
21.4%
64.6%
38.7%
22.0%
71.7%
4.5%
36.4%
14.6%
12.3%
88.8%
13.6%
60.2%
23.7%
17.3%
89.1%

1327
40.8%
61.5%
36.5%
25.0%
69.2%
12.3%
38.0%
18.4%
13.9%
84.2%
34.0%
59.8%
27.6%
19.3%
86.3%

1328
33.0%
64.7%
44.7%
37.7%
70.8%
9.3%
70.7%
36.2%
30.2%
88.6%
22.3%
75.3%
34.1%
30.0%
90.2%

1329
24.3%
58.6%
39.9%
20.9%
67.0%
7.3%
39.2%
25.4%
18.3%
85.1%
21.6%
62.7%
34.3%
19.3%
87.3%

1330
18.7%
59.4%
33.5%
29.2%
68.3%
5.0%
34.3%
15.5%
20.1%
86.3%
14.2%
65.0%
27.6%
25.1%
86.3%

1331
18.7%
58.8%
33.4%
18.6%
67.0%
4.7%
40.5%
17.0%
14.5%
86.5%
13.6%
58.9%
24.7%
17.2%
85.5%

1332
28.8%
62.9%
41.1%
34.6%
70.0%
6.5%
62.8%
18.7%
14.2%
86.2%
17.6%
68.9%
26.3%
19.6%
86.5%

1333
20.1%
66.4%
39.9%
17.6%
73.3%
4.9%
38.6%
32.5%
14.9%
87.8%
14.9%
66.4%
37.0%
15.7%
87.4%

1334
17.8%
62.2%
34.1%
31.4%
70.1%
4.9%
38.0%
16.4%
20.9%
85.6%
14.9%
65.7%
25.0%
27.7%
87.4%

1335
18.4%
63.3%
33.9%
21.9%
71.3%
5.8%
60.9%
33.1%
18.7%
88.0%
12.9%
66.2%
32.7%
19.8%
88.3%

1336
26.9%
60.9%
32.9%
27.1%
68.6%
7.8%
62.4%
18.2%
13.5%
86.6%
20.7%
69.4%
28.2%
22.4%
89.5%

1337
24.5%
60.7%
37.3%
19.8%
71.4%
8.2%
38.8%
20.7%
15.3%
87.6%
19.1%
60.2%
32.8%
17.7%
88.9%

1338
18.3%
57.5%
31.8%
29.7%
68.7%
5.2%
58.4%
19.7%
26.5%
87.6%
17.4%
67.0%
30.0%
30.9%
90.3%

1339
18.7%
57.0%
31.3%
20.7%
68.2%
7.9%
59.6%
21.0%
14.6%
87.4%
19.3%
64.5%
27.9%
21.0%
87.8%

1340
12.4%
73.3%
20.9%
23.0%
80.5%
8.7%
70.5%
13.6%
9.0%
89.0%
12.5%
73.9%
16.8%
12.0%
90.8%

1341
18.6%
61.2%
37.3%
13.4%
80.9%
8.1%
42.3%
17.7%
9.6%
90.4%
17.5%
49.8%
24.1%
11.1%
91.0%

1342
17.0%
65.0%
29.9%
39.3%
76.2%
6.7%
39.8%
14.3%
15.3%
88.1%
15.6%
55.0%
20.0%
19.8%
89.5%

1343
10.0%
65.1%
27.2%
27.2%
80.5%
5.2%
34.8%
15.3%
12.7%
85.2%
10.9%
46.9%
20.2%
13.8%
88.5%

1344
34.5%
63.5%
24.5%
22.7%
71.9%
9.2%
60.0%
16.5%
12.1%
84.7%
20.5%
67.3%
23.2%
16.8%
88.2%

1345
12.4%
61.0%
29.2%
15.1%
71.0%
6.3%
33.3%
15.7%
12.0%
83.7%
14.5%
55.1%
26.1%
14.0%
86.4%

1346
17.6%
53.3%
25.2%
29.0%
70.7%
7.1%
41.7%
16.9%
14.4%
84.5%
15.0%
51.7%
22.8%
19.0%
86.3%

1347
15.5%
45.4%
21.7%
14.9%
66.2%
6.5%
36.0%
17.4%
13.0%
80.2%
12.9%
44.5%
20.6%
13.4%
82.3%

1348
25.5%
60.2%
26.6%
18.4%
69.0%
13.2%
58.1%
16.8%
13.9%
83.7%
20.0%
63.7%
25.0%
18.3%
86.9%

1349
31.2%
50.8%
29.2%
13.5%
69.4%
10.9%
39.4%
18.3%
13.9%
84.3%
25.8%
51.2%
25.0%
16.2%
85.8%

1350
16.8%
59.1%
23.5%
22.9%
71.5%
6.4%
44.8%
15.2%
12.8%
85.7%
14.7%
54.6%
20.9%
16.3%
86.9%

1351
14.6%
56.0%
25.9%
16.7%
68.8%
7.6%
47.2%
19.0%
14.4%
85.1%
15.2%
52.5%
23.3%
17.0%
86.9%

1352
25.3%
57.8%
30.1%
18.1%
67.2%
17.3%
54.7%
18.2%
14.3%
81.4%
22.6%
63.8%
27.1%
18.4%
86.1%

1353
14.3%
59.8%
33.5%
14.0%
70.5%
6.5%
56.0%
22.7%
15.0%
86.3%
14.1%
60.5%
28.8%
15.5%
87.8%

1354
24.7%
61.1%
23.3%
17.9%
70.5%
8.8%
60.4%
23.7%
23.1%
85.7%
17.2%
63.3%
26.0%
20.4%
87.7%

1355
12.4%
64.5%
34.6%
19.7%
72.3%
5.8%
63.7%
24.8%
14.5%
86.9%
13.2%
68.8%
28.1%
17.8%
88.7%

1356
13.5%
56.3%
37.5%
15.9%
64.3%
6.2%
40.0%
20.7%
14.1%
83.3%
13.8%
59.4%
32.5%
16.3%
84.3%

1357
14.0%
57.6%
26.3%
19.3%
66.9%
6.2%
50.6%
17.8%
16.4%
84.3%
14.8%
59.7%
25.4%
18.5%
86.5%

1358
13.7%
58.6%
29.2%
17.3%
68.0%
6.9%
55.9%
21.9%
16.9%
84.3%
13.7%
60.3%
26.0%
17.3%
85.2%

1359
21.8%
59.2%
41.5%
21.8%
67.8%
11.2%
60.5%
35.7%
22.2%
86.4%
21.8%
66.8%
37.5%
21.1%
87.6%

1360
25.0%
55.9%
37.9%
13.9%
66.5%
17.8%
56.6%
39.1%
21.9%
86.0%
25.5%
61.3%
36.7%
17.2%
87.3%

1361
13.3%
59.4%
26.8%
18.6%
68.1%
6.1%
51.6%
20.2%
19.3%
85.1%
12.9%
63.1%
28.6%
20.7%
85.0%

1362
16.5%
59.8%
38.4%
16.4%
67.0%
6.1%
53.9%
22.6%
15.1%
82.4%
14.2%
63.2%
31.0%
16.9%
85.1%

1363
20.5%
57.9%
43.4%
30.2%
66.1%
6.9%
56.8%
20.7%
21.7%
83.1%
13.6%
65.2%
38.0%
26.4%
85.5%

1364
15.2%
60.3%
41.3%
19.4%
69.7%
9.3%
59.6%
35.5%
19.1%
86.2%
15.7%
64.6%
38.8%
19.6%
86.8%

1365
13.4%
59.1%
37.4%
25.5%
66.9%
6.3%
33.8%
18.0%
30.7%
81.6%
13.1%
58.2%
31.3%
29.3%
84.3%

1366
13.0%
60.0%
38.9%
18.7%
68.0%
7.4%
56.0%
23.6%
18.5%
84.7%
13.5%
63.9%
32.3%
18.6%
86.6%

1367
31.7%
61.1%
44.5%
35.0%
69.1%
11.0%
62.8%
34.3%
29.3%
85.1%
25.9%
66.8%
41.0%
30.7%
87.5%

1368
18.0%
59.2%
41.6%
21.6%
68.5%
6.6%
54.6%
30.6%
23.7%
84.7%
15.6%
64.9%
41.2%
21.3%
88.7%

1369
11.4%
65.0%
39.5%
30.7%
73.3%
5.3%
55.7%
23.2%
23.5%
85.8%
12.9%
68.0%
36.0%
27.9%
89.2%

1370
15.5%
59.8%
43.8%
27.0%
66.7%
7.9%
50.9%
22.1%
18.8%
83.1%
15.2%
64.3%
37.8%
24.9%
84.7%

1371
31.5%
61.3%
45.1%
38.0%
69.6%
9.6%
58.2%
20.7%
16.1%
84.6%
20.5%
65.5%
40.6%
32.7%
86.5%

1372
14.9%
61.5%
45.7%
33.1%
69.4%
6.9%
43.0%
24.6%
20.8%
86.1%
14.6%
62.5%
39.3%
24.3%
85.9%

1373
13.4%
57.2%
40.3%
32.5%
65.6%
6.2%
44.1%
18.2%
20.0%
84.6%
13.7%
63.4%
38.5%
30.9%
87.0%

1374
9.6%
68.8%
55.7%
41.0%
74.9%
5.2%
48.0%
16.0%
13.3%
87.5%
10.3%
66.1%
41.4%
29.4%
85.9%

1375
17.0%
58.4%
42.8%
37.8%
67.1%
6.8%
62.2%
22.7%
18.2%
85.1%
15.3%
66.4%
40.6%
35.1%
85.2%

1376
12.1%
58.1%
43.7%
32.2%
69.2%
5.4%
32.1%
18.6%
30.8%
86.4%
12.1%
59.2%
35.0%
26.7%
87.0%

1377
13.3%
58.0%
41.7%
36.1%
67.0%
5.8%
42.7%
16.2%
19.9%
84.9%
13.5%
62.3%
35.7%
30.2%
83.9%

1378
13.1%
58.0%
42.7%
30.0%
66.8%
7.3%
55.4%
25.1%
16.7%
84.8%
13.5%
63.4%
39.4%
28.7%
86.2%

1379
22.0%
64.1%
49.8%
43.2%
71.3%
8.3%
66.4%
23.0%
27.5%
86.3%
15.9%
70.2%
44.8%
40.7%
88.8%

1380
18.6%
57.2%
40.2%
28.8%
67.2%
6.8%
34.3%
21.5%
16.2%
87.6%
19.6%
64.3%
38.3%
23.7%
87.3%

1381
23.9%
57.0%
38.7%
33.9%
65.6%
6.4%
45.4%
16.9%
19.1%
84.3%
21.8%
61.6%
35.0%
30.4%
85.3%

1382
17.8%
61.9%
46.1%
31.9%
70.1%
9.4%
63.3%
30.7%
16.0%
87.4%
16.2%
67.4%
40.9%
22.9%
87.9%

1383
21.2%
64.1%
50.1%
44.1%
71.3%
8.6%
65.0%
17.6%
15.5%
85.9%
18.5%
71.5%
45.4%
41.6%
89.0%

1384
13.6%
57.0%
40.7%
30.8%
66.8%
6.7%
34.3%
18.6%
17.4%
83.9%
12.6%
61.6%
38.4%
24.2%
86.0%

1385
18.2%
63.3%
46.0%
39.6%
71.1%
7.4%
62.7%
22.3%
21.6%
87.2%
15.2%
69.0%
40.0%
36.4%
89.1%

1386
10.6%
66.1%
50.2%
39.0%
73.6%
5.1%
62.0%
26.3%
16.5%
88.4%
11.2%
69.3%
42.9%
28.5%
89.2%

1387
12.6%
59.3%
45.1%
37.7%
66.8%
5.6%
49.3%
15.7%
19.2%
84.6%
11.5%
65.8%
34.3%
32.3%
86.7%

1388
11.2%
60.8%
46.0%
33.6%
69.5%
13.3%
50.9%
28.9%
16.8%
85.7%
16.2%
63.1%
38.2%
23.5%
85.2%

1389
11.2%
64.0%
44.1%
38.4%
71.7%
4.4%
61.6%
17.5%
19.4%
86.3%
11.5%
68.5%
35.7%
33.1%
88.5%

1390
11.9%
68.4%
47.6%
33.1%
75.3%
6.7%
57.0%
22.4%
18.9%
88.8%
11.1%
70.6%
35.7%
26.4%
90.4%

1391
17.1%
69.8%
58.4%
53.5%
76.0%
10.4%
65.8%
15.6%
11.6%
86.8%
13.7%
73.5%
45.7%
41.6%
89.2%

1392
12.5%
61.5%
43.9%
30.9%
69.2%
4.7%
62.6%
41.3%
22.1%
87.3%
12.8%
67.9%
46.0%
26.2%
88.3%

1393
10.1%
70.3%
53.4%
36.8%
76.6%
4.4%
42.4%
16.1%
20.7%
86.1%
9.9%
68.7%
33.7%
25.3%
89.6%

1394
25.6%
60.7%
44.5%
39.1%
68.2%
9.4%
61.6%
16.8%
15.1%
84.9%
19.2%
70.4%
43.4%
36.5%
89.1%

1395
15.8%
62.5%
45.9%
31.7%
70.7%
7.8%
34.8%
20.4%
16.0%
86.3%
15.9%
68.4%
44.4%
23.0%
89.2%

1396
13.6%
58.4%
40.3%
35.7%
67.5%
6.2%
44.0%
18.7%
21.7%
85.8%
12.0%
65.9%
38.5%
35.5%
87.9%

1397
12.8%
62.7%
44.8%
30.4%
71.0%
5.5%
39.7%
18.6%
16.0%
85.8%
12.2%
65.3%
35.7%
25.4%
88.6%

1398
15.7%
61.9%
44.2%
37.0%
69.7%
8.1%
64.5%
25.1%
17.2%
86.8%
14.1%
70.2%
32.2%
25.6%
87.9%

1399
11.0%
63.4%
47.5%
36.6%
72.5%
4.8%
29.1%
16.3%
13.7%
86.8%
11.2%
63.9%
40.8%
23.7%
90.0%

1400
19.9%
61.2%
41.7%
36.2%
69.5%
6.5%
43.4%
17.4%
17.0%
85.5%
15.3%
65.2%
35.7%
37.0%
88.5%

1401
28.0%
63.4%
44.2%
37.9%
71.1%
9.5%
57.1%
17.3%
15.2%
83.8%
19.3%
68.7%
27.6%
22.8%
89.1%

1402
15.7%
63.0%
43.9%
29.1%
72.0%
6.9%
36.2%
22.1%
15.9%
86.0%
14.4%
62.6%
37.1%
18.2%
89.5%

1403
11.6%
59.4%
36.1%
31.6%
67.8%
11.3%
60.9%
22.2%
23.1%
86.5%
13.4%
66.0%
27.8%
26.7%
88.7%

1404
13.4%
60.4%
41.2%
29.1%
68.9%
5.2%
62.3%
22.3%
15.6%
86.6%
12.2%
66.6%
30.3%
25.9%
88.4%

1405
17.3%
64.6%
44.3%
36.7%
72.7%
9.3%
69.4%
22.4%
13.1%
90.0%
14.3%
74.0%
28.4%
21.7%
89.8%

1406
12.4%
58.2%
40.1%
23.1%
66.6%
4.7%
29.7%
18.4%
17.7%
85.7%
12.3%
55.2%
30.0%
18.4%
87.0%

1407
12.1%
60.0%
39.7%
32.3%
67.7%
4.8%
43.4%
19.0%
28.6%
86.5%
11.6%
60.4%
25.6%
27.8%
88.4%

1408
14.8%
58.1%
37.3%
25.3%
67.4%
5.5%
44.4%
19.1%
14.6%
85.7%
13.7%
57.7%
26.1%
18.7%
87.2%

1409
17.4%
63.8%
43.2%
38.2%
70.9%
5.9%
66.3%
16.0%
12.1%
87.5%
12.1%
70.3%
22.2%
17.8%
86.7%

1410
11.1%
67.6%
49.2%
22.4%
74.2%
4.2%
22.3%
14.4%
12.2%
86.9%
9.5%
55.7%
27.9%
13.5%
86.4%

1411
31.2%
78.2%
48.5%
49.2%
83.1%
4.2%
31.5%
9.5%
16.7%
90.9%
17.9%
63.4%
18.2%
29.5%
92.3%

1412
8.9%
75.3%
46.1%
28.4%
81.4%
6.2%
45.1%
13.7%
10.1%
92.4%
9.5%
60.3%
20.2%
15.9%
91.6%

1413
33.0%
63.1%
42.1%
36.6%
70.3%
6.7%
64.9%
15.6%
15.2%
87.2%
17.7%
69.6%
24.5%
20.6%
87.5%

1414
12.4%
56.4%
36.6%
18.9%
65.8%
5.3%
30.1%
17.7%
16.7%
84.8%
11.8%
58.8%
30.1%
16.0%
85.2%

1415
16.3%
64.1%
38.8%
34.1%
71.7%
6.0%
37.3%
15.6%
19.4%
88.4%
13.5%
63.4%
25.9%
26.3%
89.1%

1416
14.1%
64.6%
37.6%
22.7%
72.2%
4.9%
53.2%
20.6%
22.9%
88.9%
18.1%
64.0%
25.6%
19.3%
88.5%

1417
34.4%
60.9%
37.7%
35.3%
68.5%
8.3%
60.9%
17.5%
14.5%
83.7%
17.6%
64.3%
24.3%
18.8%
82.6%

1418
28.6%
62.6%
36.8%
17.9%
71.9%
8.4%
35.6%
20.6%
13.8%
87.7%
29.0%
63.7%
31.8%
16.3%
88.9%

1419
17.0%
63.6%
34.7%
29.6%
72.1%
10.3%
68.1%
47.0%
50.0%
88.2%
13.6%
73.7%
47.1%
46.1%
91.3%

1420
17.4%
63.3%
32.4%
20.8%
70.4%
11.0%
66.0%
44.8%
25.4%
87.1%
14.5%
72.0%
44.9%
22.3%
89.6%

1421
11.0%
55.2%
23.5%
25.5%
76.0%
5.3%
46.6%
17.0%
13.1%
87.8%
9.8%
52.9%
21.5%
20.3%
88.6%

1422
11.5%
60.4%
29.6%
26.1%
70.8%
11.5%
61.4%
18.4%
13.3%
85.3%
13.2%
68.1%
24.7%
21.0%
87.4%

1423
12.6%
55.6%
37.1%
18.1%
69.5%
6.7%
46.6%
25.2%
17.6%
86.2%
11.1%
60.1%
34.4%
16.8%
87.0%

1424
11.8%
61.3%
31.8%
30.0%
73.1%
4.8%
63.2%
16.3%
16.9%
88.9%
11.8%
65.5%
26.8%
27.9%
89.5%

1425
11.6%
58.2%
30.8%
21.0%
71.0%
6.1%
68.8%
50.7%
16.1%
87.4%
13.0%
70.5%
42.0%
18.9%
89.5%

1426
8.7%
50.7%
19.4%
25.1%
77.7%
7.4%
44.8%
17.4%
13.3%
88.3%
10.4%
51.0%
20.2%
15.8%
88.0%

1427
7.3%
67.4%
19.6%
17.9%
79.6%
12.2%
76.7%
11.8%
8.6%
90.6%
8.7%
75.9%
15.3%
11.2%
91.5%

1428
11.2%
44.6%
35.2%
16.4%
67.5%
7.1%
33.3%
18.4%
11.9%
84.0%
12.0%
45.7%
27.7%
16.5%
85.8%

1429
10.5%
58.4%
31.0%
32.5%
73.5%
6.1%
57.7%
17.5%
17.7%
87.3%
11.3%
59.1%
22.8%
21.4%
88.5%

1430
8.6%
58.5%
22.4%
16.7%
77.1%
15.5%
74.6%
23.9%
9.9%
91.0%
11.7%
72.8%
21.6%
11.2%
91.4%

1431
11.7%
49.8%
21.4%
17.5%
69.6%
6.7%
39.2%
17.4%
13.8%
84.7%
11.3%
47.7%
22.0%
15.8%
84.8%

1432
13.1%
59.3%
22.6%
15.6%
69.1%
9.4%
63.9%
23.5%
14.2%
86.2%
12.4%
65.1%
23.7%
15.3%
87.2%

1433
10.7%
53.4%
31.3%
12.5%
70.7%
8.3%
52.2%
27.3%
13.4%
85.5%
11.8%
51.9%
27.5%
13.2%
86.1%

1434
10.8%
59.4%
24.8%
21.6%
74.4%
5.9%
55.6%
17.4%
15.7%
88.2%
11.6%
56.6%
22.4%
19.2%
88.6%

1435
9.8%
56.9%
22.3%
14.2%
72.0%
9.3%
57.2%
18.2%
11.7%
87.3%
12.3%
55.7%
22.9%
14.7%
87.6%

1436
9.6%
58.5%
23.2%
17.7%
72.6%
8.5%
44.6%
17.2%
11.9%
84.0%
12.8%
52.1%
23.1%
15.7%
86.5%

1437
12.8%
61.8%
28.7%
21.4%
69.7%
11.9%
66.3%
29.2%
20.6%
87.2%
12.9%
68.9%
26.9%
19.4%
86.9%

1438
10.5%
57.9%
32.8%
12.6%
72.8%
17.0%
53.7%
24.3%
15.6%
86.2%
16.6%
56.3%
30.6%
15.6%
87.8%

1439
11.6%
59.3%
26.9%
19.0%
72.2%
5.9%
59.9%
16.7%
14.3%
85.7%
13.7%
62.3%
24.6%
18.7%
87.7%

1440
11.2%
54.7%
26.9%
17.3%
67.3%
9.8%
51.2%
20.4%
13.7%
81.5%
13.5%
56.2%
24.5%
16.0%
83.1%

1441
11.0%
59.2%
32.3%
18.8%
71.3%
5.8%
61.5%
37.7%
21.3%
85.8%
13.0%
62.1%
31.5%
19.8%
86.7%

1442
11.6%
60.6%
39.3%
19.4%
69.0%
8.7%
63.3%
45.4%
28.5%
84.9%
14.2%
67.4%
42.6%
19.6%
86.6%

1443
12.5%
57.4%
32.5%
14.3%
68.0%
8.0%
44.7%
22.5%
14.9%
84.8%
13.7%
57.6%
28.8%
15.5%
87.1%

1444
11.9%
60.7%
29.2%
20.2%
70.1%
8.5%
56.6%
18.8%
15.6%
83.7%
13.6%
63.7%
26.8%
19.4%
87.6%

1445
9.3%
64.8%
29.9%
15.3%
74.0%
9.5%
66.7%
25.4%
12.5%
86.7%
12.7%
65.7%
25.2%
14.7%
87.5%

1446
11.6%
54.7%
32.2%
19.1%
68.8%
6.3%
55.8%
25.1%
18.3%
85.2%
13.7%
60.7%
30.7%
20.4%
86.6%

1447
12.9%
57.4%
32.9%
16.1%
66.0%
8.3%
62.5%
21.0%
14.9%
83.7%
14.8%
63.5%
27.0%
16.3%
84.2%

1448
14.0%
55.6%
36.4%
15.8%
67.1%
6.3%
47.6%
29.7%
16.8%
81.2%
14.5%
59.4%
33.0%
16.7%
84.3%

1449
12.2%
50.1%
26.0%
18.8%
64.9%
6.6%
48.0%
20.0%
19.2%
82.2%
12.7%
55.4%
26.3%
19.8%
83.7%

1450
13.2%
59.3%
38.9%
17.8%
68.7%
7.9%
54.9%
21.8%
15.5%
84.4%
14.3%
62.2%
31.6%
17.0%
85.7%

1451
9.0%
65.5%
41.3%
33.8%
76.3%
6.3%
49.1%
23.4%
21.5%
85.4%
10.6%
63.2%
35.0%
30.3%
88.7%

1452
12.0%
59.1%
40.2%
21.2%
68.0%
8.6%
60.3%
28.3%
20.6%
84.9%
14.0%
65.8%
35.4%
20.2%
86.8%

1453
13.8%
56.8%
40.4%
19.4%
67.4%
6.5%
49.6%
27.2%
20.1%
82.6%
14.0%
60.8%
37.0%
19.7%
87.0%

1454
9.7%
62.2%
29.0%
21.4%
72.1%
5.6%
53.4%
21.1%
23.2%
84.2%
11.4%
62.9%
26.7%
20.9%
87.3%

1455
12.2%
58.7%
39.7%
20.0%
69.0%
5.8%
56.5%
27.9%
24.9%
86.7%
13.7%
62.0%
34.2%
22.8%
86.9%

1456
14.6%
60.4%
39.7%
24.6%
69.5%
7.8%
51.5%
29.1%
30.3%
84.7%
13.9%
61.4%
39.0%
30.6%
87.3%

1457
11.3%
57.4%
40.0%
29.6%
66.2%
8.7%
58.7%
25.1%
18.4%
84.7%
13.8%
63.1%
37.2%
26.5%
84.6%

1458
11.6%
63.4%
48.1%
22.1%
72.5%
6.2%
45.2%
27.0%
19.0%
85.0%
12.7%
65.8%
43.4%
20.5%
87.3%

1459
12.2%
62.6%
41.5%
33.5%
71.9%
5.0%
56.1%
31.4%
33.1%
85.0%
12.5%
66.2%
39.0%
32.5%
88.5%

1460
11.9%
64.0%
46.2%
20.7%
71.9%
5.8%
65.0%
47.2%
20.4%
85.5%
13.1%
69.2%
42.8%
21.9%
87.7%

1461
14.9%
65.5%
48.4%
33.0%
74.3%
9.7%
58.9%
29.5%
28.4%
85.5%
15.2%
66.5%
40.4%
29.2%
88.0%

1462
11.5%
64.3%
49.1%
39.4%
72.8%
9.0%
65.9%
49.3%
35.9%
86.6%
12.2%
70.2%
47.8%
34.9%
88.1%

1463
8.4%
71.4%
59.2%
45.6%
80.2%
4.6%
68.7%
35.9%
31.5%
89.4%
9.7%
68.7%
44.9%
29.3%
89.7%

1464
11.4%
60.1%
39.5%
32.2%
68.1%
5.8%
41.0%
16.3%
16.1%
82.6%
11.1%
60.0%
32.1%
27.0%
82.1%

1465
8.6%
66.5%
47.1%
31.0%
74.7%
5.9%
58.9%
34.5%
27.7%
84.4%
8.8%
66.0%
42.7%
30.2%
87.1%

1466
11.0%
63.0%
44.2%
35.0%
71.6%
4.7%
63.8%
41.2%
44.0%
85.9%
10.4%
66.4%
45.6%
39.5%
88.9%

1467
12.1%
63.4%
48.2%
41.8%
70.3%
9.4%
66.4%
33.7%
24.5%
86.4%
11.5%
68.2%
42.7%
36.2%
87.2%

1468
11.7%
60.4%
42.3%
30.2%
69.2%
6.2%
39.4%
20.8%
15.9%
84.3%
12.3%
64.9%
39.2%
24.6%
87.0%

1469
10.3%
65.1%
46.2%
43.0%
73.1%
5.1%
43.3%
17.8%
26.0%
86.8%
10.2%
66.7%
40.6%
37.0%
86.8%

1470
13.4%
60.5%
40.3%
30.0%
68.5%
7.4%
62.0%
24.6%
29.4%
86.6%
12.4%
65.1%
38.4%
31.3%
87.3%

1471
9.7%
60.3%
41.2%
36.8%
69.4%
6.5%
46.8%
23.4%
20.3%
84.8%
11.3%
64.4%
34.3%
31.6%
85.9%

1472
13.5%
61.6%
44.9%
38.3%
69.5%
9.9%
60.9%
21.0%
14.3%
85.0%
13.4%
67.6%
36.3%
30.7%
87.5%

1473
12.2%
56.9%
39.9%
29.5%
65.9%
6.4%
45.4%
25.3%
16.6%
84.4%
13.4%
63.0%
35.8%
23.9%
85.3%

1474
12.6%
56.6%
39.2%
34.6%
67.0%
6.4%
37.8%
18.5%
17.8%
82.5%
11.0%
62.0%
34.2%
30.7%
85.8%

1475
11.4%
64.9%
48.1%
36.9%
72.9%
5.3%
62.9%
30.0%
21.9%
86.3%
11.4%
67.6%
39.9%
30.0%
87.4%

1476
11.9%
60.4%
36.2%
31.2%
69.6%
6.4%
42.0%
19.1%
15.9%
85.0%
13.0%
62.9%
30.3%
27.7%
86.5%

1477
12.8%
59.8%
44.5%
37.2%
68.4%
6.6%
66.6%
48.2%
40.2%
86.4%
12.1%
69.2%
46.9%
37.5%
89.2%

1478
10.7%
67.5%
52.5%
37.3%
74.5%
5.7%
69.9%
50.1%
25.9%
88.8%
10.2%
71.2%
49.4%
27.7%
89.4%

1479
9.4%
68.0%
50.6%
44.4%
75.9%
4.4%
71.3%
45.5%
41.5%
89.4%
9.3%
73.7%
48.7%
41.5%
90.1%

1480
11.0%
62.9%
41.9%
30.4%
71.2%
6.6%
53.2%
18.9%
16.9%
87.3%
10.7%
65.4%
34.0%
27.4%
87.1%

1481
12.5%
61.8%
39.1%
27.3%
71.5%
6.8%
49.1%
23.5%
31.3%
86.7%
10.9%
63.1%
37.0%
33.1%
87.5%

1482
10.3%
64.5%
50.0%
41.6%
72.0%
8.1%
66.0%
26.9%
16.6%
86.7%
12.5%
70.3%
42.3%
32.0%
88.4%

1483
8.1%
65.6%
48.1%
30.4%
73.8%
6.1%
52.0%
35.3%
35.2%
87.0%
9.6%
66.3%
43.6%
29.7%
87.5%

1484
10.5%
64.8%
44.6%
37.9%
73.8%
5.8%
67.5%
29.1%
22.0%
86.7%
11.1%
69.9%
40.2%
33.0%
89.1%

1485
9.8%
67.7%
46.1%
32.8%
75.4%
6.7%
66.7%
33.5%
23.9%
89.5%
9.2%
71.1%
42.8%
33.0%
89.5%

1486
12.2%
59.5%
37.5%
32.1%
69.6%
6.3%
56.4%
25.3%
18.5%
87.9%
11.9%
64.9%
34.9%
28.9%
88.8%

1487
12.2%
65.7%
51.0%
42.7%
74.0%
7.7%
65.0%
22.7%
14.0%
85.4%
12.5%
70.7%
44.8%
34.1%
89.2%

1488
12.2%
62.7%
44.3%
28.6%
71.9%
7.0%
40.0%
22.1%
14.6%
87.1%
12.2%
64.7%
39.4%
21.6%
88.1%

1489
13.5%
59.9%
40.3%
34.5%
70.2%
5.3%
61.9%
27.7%
25.4%
86.9%
12.2%
63.2%
37.8%
31.4%
85.9%

1490
10.1%
62.2%
43.0%
32.5%
70.2%
6.4%
64.9%
36.4%
14.0%
85.5%
11.2%
66.4%
36.8%
21.7%
87.2%

1491
10.5%
56.6%
33.3%
31.9%
69.0%
5.5%
42.3%
19.2%
16.7%
86.6%
10.5%
54.0%
27.3%
28.1%
86.1%

1492
13.8%
59.9%
41.5%
35.6%
68.5%
7.3%
61.8%
18.3%
15.1%
85.7%
15.2%
68.4%
32.8%
24.8%
88.1%

1493
10.3%
63.1%
42.6%
26.8%
72.1%
5.4%
63.4%
33.0%
18.2%
88.9%
10.7%
68.6%
41.4%
19.7%
89.2%

1494
8.3%
73.0%
54.2%
39.9%
79.2%
4.7%
57.1%
17.8%
18.9%
89.1%
8.5%
67.4%
32.7%
27.8%
90.7%

1495
12.2%
57.5%
37.4%
36.1%
71.1%
7.8%
42.9%
20.7%
22.4%
85.9%
12.0%
52.9%
29.2%
32.8%
88.3%

1496
11.4%
62.4%
42.8%
34.3%
70.3%
8.9%
72.2%
48.6%
48.5%
88.3%
12.6%
72.4%
45.3%
40.1%
88.9%

1497
12.3%
60.2%
44.5%
31.3%
70.6%
6.9%
35.7%
25.6%
18.4%
87.1%
11.4%
62.9%
45.6%
26.5%
89.7%

1498
10.8%
60.6%
41.9%
37.4%
69.2%
5.1%
40.5%
14.0%
17.0%
86.4%
9.6%
57.4%
27.0%
28.9%
85.0%

1499
10.5%
65.5%
45.7%
32.0%
74.1%
5.0%
73.3%
44.0%
13.5%
89.4%
9.4%
73.4%
38.5%
24.1%
89.5%

1500
13.6%
59.0%
34.0%
27.5%
68.6%
7.3%
42.6%
17.8%
16.3%
84.5%
13.2%
52.8%
23.5%
21.9%
85.5%

1501
11.0%
63.6%
46.1%
40.8%
70.8%
8.3%
63.1%
18.0%
13.6%
85.7%
12.4%
70.8%
25.8%
20.9%
88.5%

1502
11.3%
59.7%
42.7%
25.8%
69.1%
6.0%
40.3%
25.8%
16.8%
86.5%
10.2%
55.9%
36.1%
19.0%
86.1%

1503
10.4%
57.0%
33.0%
31.4%
68.6%
4.7%
66.5%
24.1%
23.8%
86.8%
9.6%
67.8%
29.6%
30.2%
89.9%

1504
10.2%
58.9%
37.1%
25.5%
68.2%
5.5%
55.0%
21.2%
14.3%
84.4%
11.1%
60.5%
26.0%
19.7%
86.0%

1505
12.2%
60.4%
28.8%
29.6%
71.0%
6.4%
40.6%
19.0%
15.5%
87.8%
11.6%
53.0%
22.7%
21.3%
87.0%

1506
10.3%
67.5%
48.0%
42.4%
74.3%
10.2%
68.8%
25.0%
15.2%
87.7%
12.6%
69.5%
26.9%
21.2%
87.9%

1507
13.0%
58.8%
34.7%
17.8%
69.0%
6.4%
33.9%
20.9%
17.6%
88.9%
12.9%
52.8%
27.4%
17.3%
84.6%

1508
10.7%
63.8%
37.6%
36.9%
73.3%
5.0%
56.5%
22.1%
30.8%
89.9%
10.2%
62.3%
25.9%
31.2%
89.4%

1509
11.3%
61.5%
36.1%
26.1%
70.1%
6.4%
48.3%
17.9%
12.7%
86.7%
12.3%
56.0%
24.5%
17.5%
85.7%

1510
10.0%
63.3%
29.5%
33.6%
76.2%
4.0%
58.5%
26.0%
17.6%
90.8%
8.8%
63.6%
24.0%
22.8%
91.1%

1511
11.4%
64.2%
41.7%
32.3%
73.2%
14.2%
79.0%
52.7%
39.5%
92.0%
13.5%
76.3%
40.4%
29.0%
91.0%

1512
12.1%
61.1%
40.9%
20.3%
70.3%
5.5%
55.7%
30.5%
16.8%
87.5%
12.5%
60.7%
35.1%
18.7%
87.4%

1513
9.9%
64.5%
38.9%
35.7%
72.7%
3.7%
52.3%
15.8%
25.3%
91.2%
8.6%
61.9%
23.3%
30.2%
89.4%

1514
11.2%
62.9%
37.9%
24.1%
71.9%
5.6%
60.5%
19.3%
14.0%
90.0%
8.4%
64.1%
25.0%
17.7%
89.7%

1515
14.0%
62.0%
31.2%
22.4%
70.2%
7.3%
46.7%
21.5%
15.9%
86.6%
14.6%
60.1%
28.3%
20.4%
86.0%

1516
11.7%
60.6%
38.2%
30.7%
69.1%
10.8%
66.6%
24.9%
17.3%
87.3%
12.3%
64.5%
26.5%
19.6%
86.3%

1517
9.9%
66.1%
43.0%
19.9%
75.2%
5.9%
33.9%
26.0%
15.9%
89.6%
10.6%
60.8%
33.9%
15.8%
88.2%

1518
12.0%
60.2%
34.1%
29.1%
69.8%
4.2%
36.9%
15.6%
20.5%
87.5%
11.4%
62.0%
25.8%
24.8%
87.0%

1519
12.1%
62.4%
36.1%
24.2%
70.6%
6.7%
49.4%
18.4%
13.8%
87.4%
11.0%
59.2%
24.5%
18.2%
88.0%

1520
13.8%
60.5%
29.7%
24.5%
71.7%
5.9%
53.2%
25.8%
23.2%
86.5%
13.1%
60.5%
29.6%
22.8%
88.2%

1521
11.2%
63.8%
42.0%
34.1%
70.2%
6.9%
67.8%
28.1%
14.5%
85.8%
13.4%
69.0%
31.0%
20.1%
86.3%

1522
11.9%
58.4%
35.1%
18.5%
68.6%
7.8%
66.1%
49.0%
32.2%
89.4%
10.2%
67.9%
46.4%
27.7%
89.3%

1523
10.7%
65.6%
38.7%
24.4%
73.5%
5.5%
64.3%
33.5%
20.5%
88.1%
10.4%
67.4%
31.8%
21.6%
88.4%

1524
3.0%
68.2%
17.7%
15.7%
85.2%
3.9%
48.4%
17.8%
12.0%
93.9%
3.7%
42.9%
17.0%
12.2%
95.9%

1525
2.8%
7.7%
4.8%
3.2%
34.6%
1.8%
8.8%
11.3%
22.4%
83.2%
2.3%
7.1%
9.2%
16.6%
84.1%

1526
1.4%
4.8%
2.3%
1.8%
17.9%
0.7%
6.4%
19.6%
4.1%
80.9%
1.0%
6.4%
17.0%
3.2%
77.8%

1527
1.9%
5.0%
2.8%
1.9%
18.0%
1.2%
6.5%
3.8%
3.1%
29.6%
1.4%
4.7%
2.7%
1.9%
28.1%

1528
2.5%
5.9%
3.3%
2.3%
15.5%
2.3%
9.6%
5.6%
4.2%
34.7%
3.3%
7.7%
4.1%
2.9%
32.3%

1529
2.2%
5.3%
2.8%
2.0%
19.4%
1.7%
9.1%
4.5%
3.5%
22.8%
2.8%
7.7%
3.1%
2.1%
24.8%

1530
12.3%
30.6%
17.6%
11.4%
39.2%
7.0%
43.0%
23.8%
16.8%
72.2%
15.4%
49.7%
25.1%
15.4%
72.1%

1531
8.4%
7.7%
9.8%
7.9%
85.0%
1.6%
7.0%
20.0%
4.2%
94.9%
2.3%
6.7%
18.0%
4.2%
96.7%

1532
5.5%
11.0%
5.5%
4.0%
44.4%
2.6%
25.8%
6.2%
4.9%
76.9%
3.5%
19.1%
4.9%
2.9%
75.4%

1533
2.4%
5.2%
2.9%
1.8%
18.7%
1.1%
6.3%
3.8%
2.9%
42.9%
1.8%
4.5%
2.3%
1.8%
40.2%

1534
4.3%
14.8%
5.8%
3.8%
41.8%
2.7%
11.9%
6.7%
5.3%
74.1%
2.9%
11.4%
4.5%
3.2%
72.0%

1535
5.2%
12.7%
5.7%
3.6%
22.2%
6.5%
15.3%
6.6%
4.5%
51.7%
8.5%
21.1%
5.8%
3.1%
55.5%

1536
3.4%
10.7%
5.4%
3.3%
28.5%
1.9%
15.4%
6.2%
4.2%
51.6%
3.3%
18.4%
6.8%
3.8%
55.1%

1537
2.7%
9.8%
4.7%
3.0%
22.3%
1.9%
9.8%
5.4%
4.1%
30.9%
2.2%
11.9%
4.6%
2.9%
32.2%

1538
8.1%
81.4%
25.7%
5.6%
89.7%
4.6%
25.2%
35.2%
53.2%
90.0%
5.4%
30.9%
35.1%
51.6%
93.0%

1539
9.3%
77.5%
24.0%
9.5%
87.1%
4.0%
15.1%
10.8%
6.0%
73.0%
5.4%
21.9%
10.8%
5.2%
75.9%

1540
5.8%
15.5%
4.8%
2.4%
31.0%
1.3%
9.1%
5.6%
2.2%
87.8%
2.0%
10.0%
4.9%
1.7%
90.0%

1541
4.7%
24.8%
7.1%
4.5%
51.2%
2.5%
50.8%
8.3%
3.9%
81.0%
4.2%
56.6%
8.1%
3.5%
83.3%

1542
5.3%
19.1%
9.3%
5.6%
35.1%
2.9%
24.1%
9.3%
6.5%
74.1%
3.1%
26.3%
9.0%
5.2%
71.7%

1543
3.3%
14.1%
7.0%
4.4%
25.4%
1.8%
13.3%
5.6%
4.3%
51.6%
2.4%
18.7%
7.7%
4.5%
54.5%

1544
5.2%
24.4%
15.4%
9.0%
57.0%
3.0%
21.2%
12.5%
11.6%
71.3%
4.5%
24.2%
16.2%
13.2%
73.0%

1545
23.1%
88.2%
36.4%
26.7%
94.1%
11.0%
92.1%
82.3%
70.4%
97.7%
10.5%
92.5%
76.7%
61.8%
98.6%

1546
10.6%
69.3%
22.3%
12.8%
80.6%
4.9%
74.3%
32.9%
26.5%
93.9%
5.7%
78.5%
35.1%
31.9%
96.1%

1547
8.4%
69.4%
31.2%
17.2%
77.9%
4.8%
55.8%
35.7%
39.6%
90.6%
6.5%
72.5%
40.9%
37.4%
93.6%

1548
3.9%
24.9%
9.9%
8.6%
53.4%
2.0%
20.5%
6.1%
12.7%
93.3%
2.5%
30.2%
10.5%
37.6%
95.6%

1549
4.9%
28.5%
19.3%
10.9%
76.1%
3.1%
16.3%
9.8%
7.6%
90.1%
4.1%
15.8%
9.1%
6.8%
90.6%

1550
5.3%
17.8%
12.6%
10.8%
76.9%
2.8%
17.7%
8.2%
13.2%
92.4%
3.3%
14.7%
7.8%
11.4%
94.8%

1551
4.8%
13.2%
8.4%
6.2%
56.6%
2.8%
14.0%
9.7%
7.5%
63.0%
3.3%
12.1%
8.8%
5.9%
72.2%

1552
5.3%
80.6%
41.2%
33.7%
87.0%
3.9%
48.1%
32.5%
57.0%
91.7%
5.4%
69.2%
46.0%
53.5%
94.4%

1553
3.0%
40.5%
26.1%
19.6%
82.3%
2.7%
13.1%
7.4%
9.7%
95.0%
2.7%
19.8%
12.5%
13.4%
97.5%

1554
3.9%
50.9%
48.1%
43.6%
88.3%
3.5%
27.2%
8.3%
49.6%
94.8%
3.6%
48.5%
21.4%
44.1%
96.3%

1555
4.9%
38.0%
26.8%
23.9%
84.2%
3.6%
30.3%
12.6%
11.4%
83.4%
5.6%
32.9%
14.4%
14.5%
87.3%

1556
7.1%
19.4%
15.5%
8.5%
79.3%
4.0%
24.0%
13.6%
9.8%
68.4%
5.5%
20.7%
12.2%
8.1%
78.7%

1557
4.4%
10.4%
10.7%
6.2%
84.7%
3.7%
18.2%
11.2%
18.7%
92.5%
3.5%
15.4%
10.6%
24.3%
95.9%

1558
2.8%
8.2%
4.4%
3.2%
59.4%
1.8%
10.3%
6.5%
5.8%
66.4%
2.0%
7.8%
4.3%
3.5%
60.3%

1559
8.6%
25.8%
35.6%
35.0%
80.1%
5.2%
25.8%
17.7%
27.0%
90.5%
8.3%
24.7%
24.8%
31.6%
91.5%

1560
6.4%
12.5%
8.2%
43.9%
88.0%
2.4%
15.3%
8.2%
14.3%
93.0%
4.3%
14.3%
7.0%
18.4%
94.5%

1561
3.5%
8.5%
6.5%
11.5%
86.2%
2.4%
28.7%
15.7%
18.7%
88.6%
3.3%
17.7%
12.6%
12.8%
90.7%

1562
6.3%
16.9%
9.8%
7.5%
73.2%
4.8%
25.6%
15.1%
36.1%
82.2%
6.8%
22.5%
12.8%
18.8%
75.9%

1563
19.7%
23.9%
13.5%
9.7%
62.0%
6.1%
30.7%
18.3%
13.8%
83.9%
13.4%
30.6%
15.8%
12.0%
82.1%

1564
11.7%
31.2%
19.0%
13.5%
65.0%
7.4%
35.9%
20.8%
17.0%
68.6%
11.8%
35.6%
19.5%
15.0%
72.3%

1565
9.3%
26.9%
15.7%
10.6%
58.8%
5.4%
30.3%
17.3%
13.8%
65.2%
9.8%
33.2%
17.1%
13.1%
63.5%

1566
57.5%
80.8%
71.4%
62.0%
84.4%
8.9%
81.8%
21.9%
14.6%
91.4%
18.3%
87.2%
61.5%
46.1%
94.0%

1567
60.6%
84.0%
74.8%
62.6%
86.7%
10.2%
85.9%
22.9%
15.7%
93.4%
15.8%
91.2%
61.1%
44.6%
95.8%

1568
48.6%
78.1%
60.3%
55.4%
82.6%
11.6%
83.3%
26.1%
17.4%
91.9%
15.7%
88.1%
35.4%
30.0%
94.6%

1569
60.8%
87.9%
74.2%
66.2%
90.2%
12.5%
88.7%
28.0%
20.9%
94.4%
14.9%
93.4%
39.0%
34.9%
96.9%

1570
57.6%
84.0%
72.2%
63.7%
86.7%
11.5%
85.6%
26.9%
17.6%
93.2%
15.6%
91.0%
47.2%
37.4%
95.6%

1571
59.3%
83.1%
70.1%
61.7%
86.1%
11.3%
83.3%
25.7%
17.5%
92.2%
16.6%
88.3%
39.4%
33.5%
94.5%

1572
56.1%
84.5%
71.3%
63.0%
87.5%
5.8%
80.4%
17.2%
11.6%
91.7%
10.8%
89.4%
32.6%
23.5%
95.1%

1573
63.2%
90.8%
75.5%
69.6%
92.5%
13.5%
92.2%
29.7%
20.7%
96.3%
18.3%
95.3%
38.8%
35.7%
97.9%

1574
58.7%
83.8%
69.8%
63.9%
86.7%
7.8%
84.1%
20.7%
14.7%
93.1%
14.0%
89.9%
39.0%
31.5%
95.5%

1575
65.3%
88.2%
76.9%
69.9%
90.4%
8.8%
89.8%
22.7%
15.8%
95.6%
13.1%
94.2%
48.4%
38.4%
97.5%

1576
46.2%
74.7%
56.7%
50.6%
79.4%
9.7%
77.3%
25.5%
16.9%
89.3%
15.3%
84.6%
31.7%
27.0%
93.0%

1577
50.1%
76.4%
61.2%
53.0%
81.2%
10.0%
82.8%
23.9%
15.7%
92.5%
15.8%
87.3%
46.6%
38.2%
94.4%

1578
50.8%
76.6%
65.0%
58.0%
80.6%
9.3%
77.5%
22.8%
17.6%
89.3%
18.1%
81.7%
51.1%
40.8%
91.2%

1579
47.1%
76.5%
58.2%
52.4%
80.7%
9.9%
78.7%
24.7%
15.8%
91.0%
16.8%
83.5%
43.5%
34.8%
92.4%

1580
50.6%
77.7%
63.4%
55.9%
81.7%
9.5%
83.4%
25.0%
16.9%
93.7%
17.5%
86.3%
50.8%
39.0%
94.1%

1581
52.6%
81.6%
65.0%
58.1%
85.0%
11.9%
82.1%
25.8%
17.2%
92.0%
15.9%
89.2%
35.9%
30.9%
95.2%

1582
49.2%
73.9%
62.1%
56.1%
78.5%
10.3%
75.2%
21.2%
13.9%
88.4%
17.6%
78.7%
49.7%
39.0%
89.6%

1583
43.0%
75.7%
58.1%
50.7%
80.5%
10.0%
80.3%
25.3%
16.8%
91.9%
17.4%
83.8%
47.8%
36.9%
93.2%

1584
54.0%
84.5%
67.2%
58.3%
87.3%
11.7%
84.0%
26.9%
17.3%
92.8%
15.6%
89.8%
39.5%
30.8%
95.4%

1585
53.0%
82.4%
65.5%
57.4%
86.1%
8.4%
81.4%
26.1%
18.2%
91.7%
15.7%
87.9%
39.4%
32.3%
94.9%

1586
51.6%
77.2%
66.5%
59.8%
81.5%
10.0%
82.7%
24.2%
16.4%
92.4%
17.4%
85.2%
55.3%
44.5%
93.4%

1587
55.3%
83.8%
70.4%
62.3%
87.3%
10.8%
87.0%
25.8%
17.9%
94.8%
14.6%
89.2%
55.6%
42.9%
95.5%

1588
54.8%
88.5%
67.1%
61.4%
90.6%
8.9%
85.6%
28.4%
22.3%
93.3%
14.3%
91.3%
31.4%
26.8%
96.2%

1589
38.7%
74.6%
47.2%
39.5%
79.7%
9.8%
70.6%
25.9%
17.5%
86.5%
17.7%
78.5%
33.3%
25.6%
89.7%

Example 10
Selected Engineered Guide RNA Compositions Targeting DUX4

This example describes the top 50 engineered guide RNAs that target the polyadenylation (polyA) signal site (ATTAAA) in the “pLAM” region of DUX4 mRNA. The corresponding positions for each “A” in the polyA signal site sequence (ATTAAA) are denoted as 0, 3, 4, and 5. Each of these positions was targeted for editing using different engineered guide RNA sequences and the top 50 engineered guide RNAs for editing were identified. The RNA sequence for the polyA signal site is (AUUAAA). Self-annealing RNA structures, which comprised (i) the engineered guide RNAs shown in TABLE 3 and (ii) the RNA sequences of the DUX4 region targeted by the engineered guide RNAs, were contacted with ADAR1 for 30 minutes under conditions that allowed for editing. The regions targeted by the engineered guide RNAs were subsequently assessed for editing using next generation sequencing (NGS). All polynucleotide sequences encoding for the engineered guide RNAs of TABLE 3, are encompassed herein, which are represented by each of the SEQ ID NOs shown in TABLE 3, with a T substituted for each U. For each sequence, the structural features formed in the double stranded RNA substrate upon hybridization of the guide RNA to the target DUX4 RNA, are shown in the second column of TABLE 3. For reference, each structural feature formed within a guide-target RNA scaffold (target RNA sequence hybridized to an engineered guide RNA) is annotated as follows:

- a. the position of the structural feature with respect to the target A (position 0) of the target RNA sequence, with a negative value indicating upstream (5′) of the target A and a positive value indicating downstream (3′) of the target A;
- b. the number of bases in the target RNA sequence and the number of bases in the engineered guide RNA that together form the structural feature—for example, 6/6 indicates that six contiguous bases from the target RNA sequence and six contiguous bases from the engineered guide RNA form the structural feature;
- c. the name of the structural feature (e.g., symmetric bulge, symmetric internal loop, asymmetric bulge, asymmetric internal loop, mismatch, or wobble base pair), and
- d. the sequences of bases on the target RNA side and the engineered guide RNA side that participate in forming the structural feature.

For example, with reference to SEQ ID NO: 8, “20_6-6_internal_loop-symmetric_UGGAUC-ACAGGU” is read as a structural feature formed in a guide-target RNA scaffold (target DUX4 RNA sequence hybridized to an engineered guide RNA of SEQ ID NO: 8), where

- a. the structural feature starts 20 nucleotides downstream (3′) (the +20 position) from the target A (0 position) of the target RNA sequence
- b. six contiguous bases from the target RNA sequence and six contiguous bases from the engineered guide RNA form the structural feature
- c. the structural feature is an internal symmetric loop
- d. a sequence of UGGAUC from the target RNA side and a sequence of ACAGGU from the engineered guide RNA side participate in forming the internal symmetric loop.

TABLE 3

Top 50 engineered guide RNAs that target the polyadenylation (polyA)

signal site (ATTAAA) in the “pLAM” region of DUX4.

Guide

Seq ID

No:
Structural Features

Targeting Position 0

1575
-6_6-6 internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33 6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_3-3 bulge-

symmetric_UGU-CUU; 62_3-3_bulge-symmetric_GAG-GAG; 75_3-3_bulge-

symmetricAUA-GUG

593
-9_6-6_internal_loop-symmetric_UAGUUC-CGUGAU; 0_1-1_mismatch_A-

C; 40_6-6_internal_loop-symmetric_CAUCUU-CCCUCC

1573
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_5-

5_internal_loop-symmetric_UGUGU-UGAAU; 60_5-5_internal_loop-

symmetric_CAGAG-GCACC; 73_5-5_internal_loop-symmetric_CAAUA-

AAGUC

934
-6_6-6_internal_loop-symmetric_UUCAGA-CACCUC; 0_1-1_mismatch_A-C;

33_6-6_internal_loop-symmetric_AGAUUU-UCCCUA

1569
-6_6-6 internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_5-

5_internal_loop-symmetric_UUUGU-UGUUC; 56_5-5_internal_loop-

symmetric_AGUGC-CUUUC; 67_5-5_internal_loop-symmetric_AUGUC-

CCAAA

1567
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_3-3_bulge-

symmetric_UUU-UAU; 54_3-3_bulge-symmetric_UGA-CUU; 63_3-3_bulge-

symmetric_AGA-GAC; 72_3-3_bulge-symmetric_ACA-GCA

851
-7_6-6_internal_loop-symmetric_GUUCAG-ACGUCG; 0_1-1_mismatch_A-C;

42_6-6_internal_loop-symmetric_UCUUUU-CCGCUC

1211
-4_6-6_internal_loop-symmetric_CAGAGA-ACAGGC; 0_1-1_mismatch_A-C;

42_6-6_internal_loop-symmetric_UCUUUU-CCCCUC

1571
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_3-3_bulge-

symmetric_UGU-UGU; 58_3-3_bulge-symmetric_UGC-AAU; 69_3-3_bulge-

symmetric_GUC-CCA

937
-6_6-6_internal_loop-symmetric_UUCAGA-AUAAGU; 0_1-1_mismatch_A-

C; 40_6-6_internal_loop-symmetric_CAUCUU-UGCUCC

1574
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_2-2_bulge-

symmetric_UG-GC; 61_2-2_bulge-symmetric_AG-AA; 73_2-2_bulge-

symmetric_CA-AC

1570
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_2-2_bulge-

symmetric_UG-AU; 57_2-2_bulge-symmetric_GU-CG; 67_2-2_bulge-

symmetric_AU-UA; 77_2-2_bulge-symmetric_AU-UG

1566
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_2-2_bulge-

symmetric_UU-CC; 53_2-2_bulge-symmetric_AU-CG; 61_2-2_bulge-

symmetric_AG-GA; 69_2-2_bulge-symmetric_GU-UG; 77_2-2_bulge-

symmetric_AU-CC

1117
-4_6-6_internal_loop-symmetric_CAGAGA-GUAAUC; 0_1-1_mismatch_A-

C; 23_6-6_internal_loop-symmetric_AUCCUA-CCUUUC

906
-6_6-6_internal_loop-symmetric_UUCAGA-AGCUCC; 0_1-1_mismatch_A-C;

27_6-6_internal_loop-symmetric_UAUAGA-GUGGGC

1572
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_4-4_bulge-

symmetric_UGUG-ACCU; 59_4-4_bulge-symmetric_GCAG-GGUG; 71_4-

4_bulge-symmetric_CACA-CUUU

1104
-5_6-6_internal_loop-symmetric_UCAGAG-GGGUCC; 3_1-1_mismatch A-C;

44_6-6_internal_loop-symmetric_UUUUGU-UGCCCC

352
-11_6-6_internal_loop-symmetric_AUUAGU-UAAGUC; 0_1-1_mismatch_A-

C; 41_6-6_internal_loop-symmetric_AUCUUU-UUCCCC

512
-9_6-6_internal_loop-symmetric_UAGUUC-AUCAUU; 0_1-1_mismatch_A-

C; 22_6-6_internal_loop-symmetric_GAUCCU-UCUCCG

1587
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_3-3_bulge-

symmetric_GAG-GCG; 74_3-3_bulge-symmetric_AAU-UCA

375
-10_6-6_internal_loop-symmetric_UUAGUU-UUGAUU; 0_1-1_mismatch_A-

C; 20_6-6_internal_loop-symmetric_UGGAUC-UGCGGU

1588
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_4-4_bulge-

symmetric_GAGU-CAAA; 75_4-4_bulge-symmetric_AUAU-CGCG

977
-6_6-6_internal_loop-symmetric_UUCAGA-AGCAUC; 3_1-1_mismatch_A-C;

42_6-6_internal_loop-symmetric_UCUUUU-CUGUCC

642
-8_6-6_internal_loop-symmetric_AGUUCA-AUUGUA; 0_1-1_mismatch_A-

C; 24_6-6 internal_loop-symmetric_UCCUAU-CCUUUU

1236
-3_6-6_internal_loop-symmetric_AGAGAU-UAGAAA; 0_1-1_mismatch_A-

C; 24_6-6_internal_loop-symmetric_UCCUAU-CCUUCU

1584
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_4-4_bulge-

symmetric_AUGA-AGCC; 71_4-4_bulge-symmetric_CACA-AUAA

252
-11_6-6_internal_loop-symmetric_AUUAGU-UAAUCC; 0_1-1 mismatch_A-

C; 20_6-6_internal_loop-symmetric_UGGAUC-AGCGGU

394
-10_6-6_internal_loop-symmetric_UUAGUU-UUACAC; 0_1-1_mismatch_A-

C; 24_6-6_internal_loop-symmetric_UCCUAU-UCAUCC

482
-10_6-6_internal_loop-symmetric_UUAGUU-UUACAU; 0_1-1 mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-UACGCC

1585
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_5-

5_internal_loop-symmetric_AUGAG-GAAAA; 72_5-5_internal_loop-

symmetric_ACAAU-UCAAG

291
-11_6-6_internal_loop-symmetric_AUUAGU-UGAGCA; 0_1-1_mismatch_A-

C; 28_6-6_internal_loop-symmetric_AUAGAA-CCUCCA

356
-11_6-6_internal_loop-symmetric_AUUAGU-CGACCG; 0_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-UCCUUU

1054
-5_6-6_internal_loop-symmetric_UCAGAG-GAGAUC; 33_6-6_internal_loop-

symmetric_AGAUUU-CCUGGA

1581
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_5-

5_internal_loop-symmetric_UGAUG-GUAGU; 68_5-5_internal_loop-

symmetric_UGUCA-GCAGU

1103
-5_6-6_internal_loop-symmetric_UCAGAG-GCAGCU; 0_1-1_mismatch_A-C;

44_6-6 internal_loop-symmetric_UUUUGU-CUACUC

502
-9_6-6_internal_loop-symmetric_UAGUUC-UUUUGC; 0_1-1_mismatch_A-

C; 20_6-6_internal_loop-symmetric_UGGAUC-ACUAUU

769
-7 6-6_internal_loop-symmetric_GUUCAG-AAAAUA; 0_1-1_mismatch_A-

C; 25_6-6_internal_loop-symmetric_CCUAUA-GACUCC

408
-10_6-6_internal_loop-symmetric_UUAGUU-CCUCGC; 0_1-1_mismatch_A-

C; 27_6-6_internal_loop-symmetric_UAUAGA-AACCCC

1586
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_2-2_bulge-

symmetric_GA-AA; 73_2-2_bulge-symmetric_CA-CC

1008
-5_6-6_internal_loop-symmetric_UCAGAG-GAGAGU; 0_1-1_mismatch_A-

C; 24_6-6_internal_loop-symmetric_UCCUAU-UUUUCU

737
-8_6-6_internal_loop-symmetric_AGUUCA-GGUUUC; 0_1-1_mismatch_A-

C; 44_6-6_internal_loop-symmetric_UUUUGU-UGCCGU

985
-6_6-6_internal_loop-symmetric_UUCAGA-GGGCCU; 0_1-1_mismatch_A-C;

44_6-6_internal_loop-symmetric_UUUUGU-UUGGUC

679
-8_6-6_internal_loop-symmetric_AGUUCA-ACCUAG; 0_1-1_mismatch_A-C;

32_6-6_internal_loop-symmetric_AAGAUU-CUAACC

727
-8_6-6_internal_loop-symmetric_AGUUCA-ACUUCG; 0_1-1_mismatch_A-C;

42 6-6 internal loop-symmetric_UCUUUU-CUCGAU

1578
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_2-2_bulge-

symmetric_UG-GC; 65_2-2_bulge-symmetric_AU-UG

365
-11_6-6_internal_loop-symmetric_AUUAGU-CCAAAG; 0_1-1_mismatch_A-

C; 44_6-6_internal_loop-symmetric_UUUUGU-UAACCU

1580
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1 mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_4-4_bulge-

symmetric_UGAU-CUAC; 67_4-4_bulge-symmetric_AUGU-UGUC

487
-10_6-6_internal_loop-symmetric_UUAGUU-CCUCAC; 0_1-1_mismatch_A-

C; 43_6-6_internal_loop-symmetric_CUUUUG-AUCGCU

1098
-5_6-6_internal_loop-symmetric_UCAGAG-GCGACC; 0_1-1_mismatch_A-C;

43_6-6_internal_loop-symmetric_CUUUUG-GCACCC

976
-6_6-6_internal_loop-symmetric_UUCAGA-GUGUUU; 0_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-CGUCGU

Targeting Position 3

1573
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_5-

5_internal_loop-symmetric_UGUGU-UGAAU; 60_5-5_internal_loop-

symmetric_CAGAG-GCACC; 73_5-5_internal_loop-symmetric_CAAUA-

AAGUC

1588
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_4-4_bulge-

symmetric_GAGU-CAAA; 75_4-4_bulge-symmetric_AUAU-CGCG

1545
-5_2-2_bulge-symmetric_AG-GC; 10_2-2_bulge-symmetric_CC-AU; 26_2-

2_bulge-symmetric_CU-UU; 42_2-2_bulge-symmetric_UC-CC; 58_2-2_bulge-

symmetric_UG-GU; 74_2-2_bulge-symmetric_AA-AG

1575
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_3-3_bulge-

symmetric_UGU-CUU; 62_3-3_bulge-symmetric_GAG-GAG; 75_3-3_bulge-

symmetric_AUA-GUG

1569
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_5-

5_internal_loop-symmetric_UUUGU-UGUUC; 56_5-5_internal_loop-

symmetric_AGUGC-CUUUC; 67_5-5_internal_loop-symmetric_AUGUC-

CCAAA

1584
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_4-4_bulge-

symmetric_AUGA-AGCC; 71_4-4_bulge-symmetric_CACA-AUAA

1572
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_4-4_bulge-

symmetric_UGUG-ACCU; 59_4-4_bulge-symmetric_GCAG-GGUG; 71_4-

4_bulge-symmetric_CACA-CUUU

1567
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_3-3_bulge-

symmetric_UUU-UAU; 54_3-3_bulge-symmetric_UGA-CUU; 63_3-3_bulge-

symmetric_AGA-GAC; 72_3-3 bulge-symmetric_ACA-GCA

1570
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_2-2_bulge-

symmetric_UG-AU; 57_2-2_bulge-symmetric_GU-CG; 67_2-2_bulge-

symmetric_AU-UA; 77_2-2 bulge-symmetric_AU-UG

1587
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_3-3_bulge-

symmetric_GAG-GCG; 74_3-3_bulge-symmetric_AAU-UCA

1574
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_2-2_bulge-

symmetric_UG-GC; 61_2-2_bulge-symmetric_AG-AA; 73_2-2_bulge-

symmetric_CA-AC

625
-8_6-6_internal_loop-symmetric_AGUUCA-CAGUUC; 5_1-1_mismatch_A-C;

20_6-6_internal_loop-symmetric_UGGAUC-AAGUGU

1571
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_3-3_bulge-

symmetric_UGU-UGU; 58_3-3_bulge-symmetric_UGC-AAU; 69_3-3_bulge-

symmetric_GUC-CCA

874
-6_6-6_internal_loop-symmetric_UUCAGA-AGGCUU; 5_1-1_mismatch_A-

C; 20_6-6_internal_loop-symmetric_UGGAUC-UUGUGU

17
3_1-1_mismatch_A-C; 22 6-6_internal_loop-symmetric_GAUCCU-CCCCGA

1585
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_5-

5_internal_loop-symmetric_AUGAG-GAAAA; 72_5-5_internal_loop-

symmetric_ACAAU-UCAAG

757
-7_6-6_internal_loop-symmetric_GUUCAG-AAGCAA; 5_1-1_mismatch_A-

C; 22_6-6_internal_loop-symmetric_GAUCCU-UUCCCG

1581
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_5-

5_internal_loop-symmetric_UGAUG-GUAGU; 68_5-5_internal_loop-

symmetric_UGUCA-GCAGU

1538
-7_2-2_bulge-symmetric_AG-GA; 6_2-2_bulge-symmetric_AU-UC; 20_2-

2_bulge-symmetric_UG-AU; 34_2-2_bulge-symmetric_GA-CA; 48_2-

2_bulge-symmetric_GU-CG; 62_2-2_bulge-symmetric_GA-GA; 76_2-

2_bulge-symmetric_UA-CC

8
3_1-1_mismatch_A-C; 20_6-6_internal_loop-symmetric_UGGAUC-ACAGGU

1002
-5_6-6_internal_loop-symmetric_UCAGAG-AAGGCU; 5_1-1_mismatch_A-

C; 22_6-6_internal_loop-symmetric_GAUCCU-CCCUAA

1566
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_2-2_bulge-

symmetric_UU-CC; 53_2-2_bulge-symmetric_AU-CG; 61_2-2_bulge-

symmetric_AG-GA; 69_2-2_bulge-symmetric_GU-UG; 77_2-2_bulge-

symmetric AU-CC

486
-10_6-6_internal_loop-symmetric_UUAGUU-CCAGUC; 42_6-

6_internal_loop-symmetric_UCUUUU-UGUCCC

1552
-3_2-2_bulge-symmetric_AU-CA; 14_2-2_bulge-symmetric_UC-UU; 32_2-

2_bulge-symmetric_AA-GG; 50_2-2_bulge-symmetric_GU-CG; 68_2-

2_bulge-symmetric_UG-GC

505
-9_6-6_internal_loop-symmetric_UAGUUC-ACGUCC; 5_1-1_mismatch_A-C;

20_6-6_internal_loop-symmetric_UGGAUC-UCGGGU

635
-8_6-6_internal_loop-symmetric_AGUUCA-GAUUGA; 5_1-1_mismatch_A-

C; 22_6-6_internal_loop-symmetric_GAUCCU-CCCUGG

606
-9_6-6_internal_loop-symmetric_UAGUUC-AUUUUU; 42_6-6_internal_loop-

symmetric_UCUUUU-CCUCAC

884
-6_6-6_internal_loop-symmetric_UUCAGA-GGUUAU; 5_1-1_mismatch_A-

C; 22_6-6_internal_loop-symmetric_GAUCCU-CCUCCA

1054
-5_6-6_internal_loop-symmetric_UCAGAG-GAGAUC; 33_6-6_internal_loop-

symmetric_AGAUUU-CCUGGA

880
-6_6-6_internal_loop-symmetric_UUCAGA-ACCUUC; 21_6-6_internal_loop-

symmetric_GGAUCC-CUCGAG

1411
-2_6-6_internal_loop-symmetric_GAGAUA-AGCGGG; 5_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-CCUCCC

1568
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_4-4_bulge-

symmetric_UUUG-GUAU; 55_4-4_bulge-symmetric_GAGU-CAAG; 65_4-

4_bulge-symmetric_AUAU-CAAA; 75_4-4_bulge-symmetric_AUAU-UUCG

871
-6_6-6_internal_loop-symmetric_UUCAGA-GUUCAC; 0_1-1_mismatch_A-C;

20_6-6_internal_loop-symmetric_UGGAUC-CUGUGU

1580
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_4-4_bulge-

symmetric_UGAU-CUAC; 67_4-4_bulge-symmetric_AUGU-UGUC

1539
-6_3-3_bulge-symmetric_AGA-CAG; 7_3-3_bulge-symmetric_UGC-AAC;

22_3-3_bulge-symmetric_GAU-UAG; 37_3-3_bulge-symmetric_UUG-GUU;

52_3-3_bulge-symmetric_GAU-CGG; 67_3-3_bulge-symmetric_AUG-ACC

14
5_1-1_mismatch_A-C; 21_6-6_internal_loop-symmetric_GGAUCC-UCGCGG

892
-6_6-6_internal_loop-symmetric_UUCAGA-AAUCGC; 3_1-1_mismatch_A-C;

24_6-6_internal_loop-symmetric_UCCUAU-UGACCU

1116
-4_6-6_internal_loop-symmetric_CAGAGA-CGAAAC; 22_6-6_internal_loop-

symmetric_GAUCCU-CCCCAG

15
21_6-6_internal_loop-symmetric_GGAUCC-CCCCAA

1586
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_2-2_bulge-

symmetric_GA-AA; 73_2-2_bulge-symmetric_CA-CC

593
-9_6-6_internal_loop-symmetric_UAGUUC-CGUGAU; 0_1-1_mismatch_A-

C; 40_6-6_internal_loop-symmetric_CAUCUU-CCCUCC

10
5_1-1_mismatch_A-C; 20_6-6_internal_loop-symmetric_UGGAUC-UUAGAU

977
-6_6-6_internal_loop-symmetric_UUCAGA-AGCAUC; 3_1-1_mismatch_A-C;

42_6-6_internal_loop-symmetric_UCUUUU-CUGUCC

1578
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_2-2_bulge-

symmetric_UG-GC; 65_2-2_bulge-symmetric_AU-UG

1579
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_3-3_bulge-

symmetric_UGA-AGC; 66_3-3_bulge-symmetric_UAU-UAC

747
-7_6-6_internal_loop-symmetric_GUUCAG-AAAUUG; 3_1-1_mismatch_A-

C; 20_6-6_internal_loop-symmetric_UGGAUC-AAAAGU

1577
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1 mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_5-

5_internal_loop-symmetric_UGUGA-GCCUU; 64_5-5_internal_loop-

symmetric_GAUAU-CUUAA

748
-7_6-6_internal_loop-symmetric_GUUCAG-ACGUCG; 5_1-1_mismatch_A-C;

20_6-6_internal_loop-symmetric_UGGAUC-CGCAAU

873
-6_6-6_internal_loop-symmetric_UUCAGA-CAUUAU; 4_1-1_mismatch_A-

C; 20_6-6_internal_loop-symmetric_UGGAUC-AGCGUU

494
-10_6-6_internal_loop-symmetric_UUAGUU-CGUACC; 4_1-1_mismatch_A-

C; 44_6-6_internal_loop-symmetric_UUUUGU-CCCUCC

Targeting Position 4

1575
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_3-3_bulge-

symmetric_UGU-CUU; 62_3-3_bulge-symmetric_GAG-GAG; 75_3-3_bulge-

symmetric_AUA-GUG

1573
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_5-

5_internal_loop-symmetric_UGUGU-UGAAU; 60_5-5_internal_loop-

symmetric_CAGAG-GCACC; 73_5-5_internal_loop-symmetric_CAAUA-

AAGUC

1567
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_3-3_bulge-

symmetric_UUU-UAU; 54_3-3_bulge-symmetric_UGA-CUU; 63_3-3_bulge-

symmetric_AGA-GAC; 72_3-3_bulge-symmetric_ACA-GCA

1569
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_5-

5_internal_loop-symmetric_UUUGU-UGUUC; 56_5-5_internal_loop-

symmetric_AGUGC-CUUUC; 67_5-5_internal_loop-symmetric_AUGUC-

CCAAA

1570
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_2-2_bulge-

symmetric_UG-AU; 57_2-2_bulge-symmetric_GU-CG; 67_2-2_bulge-

symmetric_AU-UA; 77_2-2_bulge-symmetric_AU-UG

1566
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_2-2_bulge-

symmetric_UU-CC; 53_2-2_bulge-symmetric_AU-CG; 61_2-2_bulge-

symmetric_AG-GA; 69_2-2_bulge-symmetric_GU-UG; 77_2-2_bulge-

symmetric_AU-CC

1572
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_4-4_bulge-

symmetric_UGUG-ACCU; 59_4-4_bulge-symmetric_GCAG-GGUG; 71_4-

4_bulge-symmetric_CACA-CUUU

1587
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_3-3_bulge-

symmetric_GAG-GCG; 74_3-3 bulge-symmetric_AAU-UCA

1571
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_3-3_bulge-

symmetric_UGU-UGU; 58_3-3_bulge-symmetric_UGC-AAU; 69_3-3_bulge-

symmetric_GUC-CCA

1574
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_2-2_bulge-

symmetric_UG-GC; 61_2-2_bulge-symmetric_AG-AA; 73_2-2_bulge-

symmetric_CA-AC

1584
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_4-4_bulge-

symmetric_AUGA-AGCC; 71_4-4_bulge-symmetric_CACA-AUAA

1588
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_4-4_bulge-

symmetric_GAGU-CAAA; 75_4-4_bulge-symmetric_AUAU-CGCG

1054
-5_6-6_internal_loop-symmetric_UCAGAG-GAGAUC; 33_6-6_internal_loop-

symmetric_AGAUUU-CCUGGA

1586
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_2-2_bulge-

symmetric_GA-AA; 73_2-2_bulge-symmetric_CA-CC

1585
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_5-

5_internal_loop-symmetric_AUGAG-GAAAA; 72_5-5_internal_loop-

symmetric_ACAAU-UCAAG

1581
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_5-

5_internal_loop-symmetric_UGAUG-GUAGU; 68_5-5_internal_loop-

symmetric_UGUCA-GCAGU

1578
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_2-2_bulge-

symmetric_UG-GC; 65_2-2_bulge-symmetric_AU-UG

1580
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_4-4_bulge-

symmetric_UGAU-CUAC; 67_4-4_bulge-symmetric_AUGU-UGUC

934
-6_6-6_internal_loop-symmetric_UUCAGA-CACCUC; 0_1-1_mismatch_A-C;

33_6-6_internal_loop-symmetric_AGAUUU-UCCCUA

72
3_1-1_mismatch_A-C; 33_6-6_internal_loop-symmetric_AGAUUU-

UUGGGA

1582
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_2-2_bulge-

symmetric_AU-UA; 69_2-2_bulge-symmetric_GU-UA

1066
-5_6-6_internal_loop-symmetric_UCAGAG-AAUUAC; 3_1-1_mismatch_A-

C; 36_6-6_internal_loop-symmetric_UUUGCA-CUCCUC

1183
-4_6-6_internal_loop-symmetric_CAGAGA-AUGGCC; 3_1-1_mismatch_A-C;

36_6-6_internal_loop-symmetric_UUUGCA-GAAUCC

1577
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_5-

5_internal_loop-symmetric_UGUGA-GCCUU; 64_5-5_internal_loop-

symmetric_GAUAU-CUUAA

967
-6_6-6_internal_loop-symmetric_UUCAGA-AUAAGU; 0_1-1_mismatch_A-

C; 40_6-6_internal_loop-symmetric_CAUCUU-UGCUCC

1568
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_4-4_bulge-

symmetric_UUUG-GUAU; 55_4-4_bulge-symmetric_GAGU-CAAG; 65_4-

4_bulge-symmetric_AUAU-CAAA; 75_4-4_bulge-symmetric_AUAU-UUCG

930
-6_6-6_internal_loop-symmetric_UUCAGA-CAACAC; 3_1-1 mismatch_A-C;

32 6-6_internal_loop-symmetric_AAGAUU-UUGGCC

566
-9_6-6_internal_loop-symmetric_UAGUUC-UCCACC; 3_1-1_mismatch_A-C;

34 6-6_internal_loop-symmetric_GAUUUG-AUUGGG

1463
-1_6-6_internal_loop-symmetric_AGAUAU-UCCCUG; 4_1-1_mismatch_A-C;

32_6-6 internal_loop-symmetric_AAGAUU-CAGGGG

1294
-3_6-6_internal_loop-symmetric_AGAGAU-UCAAAC; 4_1-1_mismatch_A-

C; 36_6-6_internal_loop-symmetric_UUUGCA-CCCCUC

1293
-3_6-6_internal_loop-symmetric_AGAGAU-CCAGGG; 3_1-1_mismatch_A-

C; 36_6-6_internal_loop-symmetric_UUUGCA-GGGUCC

1391
-2_6-6_internal_loop-symmetric_GAGAUA-GCGGAG; 3_1-1_mismatch_A-

C; 37_6-6_internal_loop-symmetric_UUGCAU-CACCCU

1579
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_3-3_bulge-

symmetric_UGA-AGC; 66_3-3_bulge-symmetric_UAU-UAC

1583
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_3-3_bulge-

symmetric_AUG-GCG; 70_3-3_bulge-symmetric_UCA-AUU

944
-6_6-6_internal_loop-symmetric_UUCAGA-GAAUUC; 3_1-1_mismatch_A-

C; 35_6-6_internal_loop-symmetric_AUUUGC-UAUGCC

815
-7_6-6_internal_loop-symmetric_GUUCAG-GCCCCG; 3_1-1_mismatch_A-C;

34_6-6 internal_loop-symmetric_GAUUUG-GCCUGG

1168
-4_6-6_internal_loop-symmetric_CAGAGA-GUAGUC; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CGCGGA

593
-9_6-6_internal_loop-symmetric_UAGUUC-CGUGAU; 0_1-1_mismatch_A-

C; 40_6-6_internal_loop-symmetric_CAUCUU-CCCUCC

594
-9_6-6_internal_loop-symmetric_UAGUUC-UCUUGC; 3_1-1_mismatch_A-C;

40_6-6_internal_loop-symmetric_CAUCUU-CCUUCC

694
-8_6-6_internal_loop-symmetric_AGUUCA-ACUCGA; 3_1-1_mismatch_A-C;

35_6-6_internal_loop-symmetric_AUUUGC-CUUCCC

1576
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_4-4_bulge-

symmetric_UGUG-GUAU; 63_4-4_bulge-symmetric_AGAU-UGGC

1193
-4_6-6_internal_loop-symmetric_CAGAGA-CGGGCA; 4_1-1_mismatch_A-C;

38_6-6_internal_loop-symmetric_UGCAUC-CCCCCU

1051
-5_6-6_internal_loop-symmetric_UCAGAG-AGAUAC; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CGCCCC

1212
-4_6-6_internal_loop-symmetric_CAGAGA-GACAUU; 3_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-UCGUCC

806
-7_6-6_internal_loop-symmetric_GUUCAG-GGCUAA; 4_1-1_mismatch_A-

C; 32_6-6_internal_loop-symmetric_AAGAUU-CCUGCC

1059
-5_6-6_internal_loop-symmetric_UCAGAG-AUACCC; 34_6-6_internal_loop-

symmetric_GAUUUG-GUUGGG

1374
-2_6-6_internal_loop-symmetric_GAGAUA-CGAGGG; 32_6-6_internal_loop-

symmetric_AAGAUU-CGACCC

195
-12_6-6_internal_loop-symmetric_GAUUAG-GCCCGG; 5_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-UCGGGA

358
-11_6-6_internal_loop-symmetric_AUUAGU-CCCUCG; 4_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-UCCCUC

1296
-3_6-6_internal_loop-symmetric_AGAGAU-UGGAUG; 36_6-6_internal_loop-

symmetric_UUUGCA-AAAACC

Targeting Position 5

1575
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_3-3_bulge-

symmetric_UGU-CUU; 62_3-3_bulge-symmetric_GAG-GAG; 75_3-3_bulge-

symmetric_AUA-GUG

1573
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_5-

5_internal_loop-symmetric_UGUGU-UGAAU; 60_5-5_internal_loop-

symmetric_CAGAG-GCACC; 73_5-5_internal_loop-symmetric_CAAUA-

AAGUC

1569
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_5-

5_internal_loop-symmetric_UUUGU-UGUUC; 56_5-5_internal_loop-

symmetric_AGUGC-CUUUC; 67_5-5_internal_loop-symmetric_AUGUC-

CCAAA

1574
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1 mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_2-2_bulge-

symmetric_UG-GC; 61_2-2_bulge-symmetric_AG-AA; 73_2-2_bulge-

symmetric_CA-AC

1570
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1 mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_2-2_bulge-

symmetric_UG-AU; 57_2-2_bulge-symmetric_GU-CG; 67_2-2_bulge-

symmetric_AU-UA; 77_2-2_bulge-symmetric_AU-UG

1572
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_4-4_bulge-

symmetric_UGUG-ACCU; 59_4-4_bulge-symmetric_GCAG-GGUG; 71_4-

4_bulge-symmetric_CACA-CUUU

1567
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_3-3_bulge-

symmetric_UUU-UAU; 54_3-3_bulge-symmetric_UGA-CUU; 63_3-3_bulge-

symmetric_AGA-GAC; 72_3-3_bulge-symmetric_ACA-GCA

1587
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_3-3_bulge-

symmetric_GAG-GCG; 74_3-3_bulge-symmetric_AAU-UCA

1566
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_2-2_bulge-

symmetric_UU-CC; 53_2-2_bulge-symmetric_AU-CG; 61_2-2_bulge-

symmetric_AG-GA; 69_2-2_bulge-symmetric_GU-UG; 77_2-2_bulge-

symmetric_AU-CC

1571
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 47_3-3_bulge-

symmetric_UGU-UGU; 58_3-3_bulge-symmetric_UGC-AAU; 69_3-3_bulge-

symmetric_GUC-CCA

1588
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_4-4_bulge-

symmetric_GAGU-CAAA; 75_4-4_bulge-symmetric_AUAU-CGCG

72
3_1-1_mismatch_A-C; 33_6-6_internal_loop-symmetric_AGAUUU-

UUGGGA

1586
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 55_2-2_bulge-

symmetric_GA-AA; 73_2-2_bulge-symmetric_CA-CC

1584
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_4-4_bulge-

symmetric_AUGA-AGCC; 71_4-4_bulge-symmetric_CACA-AUAA

1581
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_5-

5_internal_loop-symmetric_UGAUG-GUAGU; 68_5-5_internal_loop-

symmetric_UGUCA-GCAGU

1578
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1 mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_2-2_bulge-

symmetric_UG-GC; 65_2-2_bulge-symmetric_AU-UG

1585
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_5-

5_internal_loop-symmetric_AUGAG-GAAAA; 72_5-5_internal_loop-

symmetric_ACAAU-UCAAG

1582
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_2-2_bulge-

symmetric_AU-UA; 69_2-2_bulge-symmetric_GU-UA

1580
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_4-4_bulge-

symmetric_UGAU-CUAC; 67_4-4_bulge-symmetric_AUGU-UGUC

1183
-4_6-6_internal_loop-symmetric_CAGAGA-AUGGCC; 3_1-1_mismatch_A-C;

36 6-6_internal_loop-symmetric_UUUGCA-GAAUCC

1568
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 45_4-4_bulge-

symmetric_UUUG-GUAU; 55_4-4_bulge-symmetric_GAGU-CAAG; 65_4-

4_bulge-symmetric_AUAU-CAAA; 75_4-4_bulge-symmetric_AUAU-UUCG

1066
-5_6-6_internal_loop-symmetric_UCAGAG-AAUUAC; 3_1-1_mismatch_A-

C; 36_6-6_internal_loop-symmetric_UUUGCA-CUCCUC

1391
-2_6-6_internal_loop-symmetric_GAGAUA-GCGGAG; 3_1-1_mismatch_A-

C; 37_6-6_internal_loop-symmetric_UUGCAU-CACCCU

1168
-4_6-6_internal_loop-symmetric_CAGAGA-GUAGUC; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CGCGGA

1293
-3_6-6_internal_loop-symmetric_AGAGAU-CCAGGG; 3_1-1_mismatch_A-

C; 36_6-6_internal_loop-symmetric_UUUGCA-GGGUCC

1577
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_5-

5_internal_loop-symmetric_UGUGA-GCCUU; 64_5-5_internal_loop-

symmetric_GAUAU-CUUAA

1054
-5_6-6_internal_loop-symmetric_UCAGAG-GAGAUC; 33_6-6_internal_loop-

symmetric_AGAUUU-CCUGGA

566
-9_6-6_internal_loop-symmetric_UAGUUC-UCCACC; 3_1-1_mismatch_A-C;

34_6-6_internal_loop-symmetric_GAUUUG-AUUGGG

1579
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 51_3-3_bulge-

symmetric_UGA-AGC; 66_3-3_bulge-symmetric_UAU-UAC

930
-6_6-6_internal_loop-symmetric_UUCAGA-CAACAC; 3_1-1_mismatch_A-C;

32_6-6_internal_loop-symmetric_AAGAUU-UUGGCC

694
-8_6-6_internal_loop-symmetric_AGUUCA-ACUCGA; 3_1-1_mismatch_A-C;

35_6-6 internal_loop-symmetric_AUUUGC-CUUCCC

944
-6_6-6_internal_loop-symmetric_UUCAGA-GAAUUC; 3_1-1_mismatch_A-

C; 35_6-6_internal_loop-symmetric_AUUUGC-UAUGCC

195
-12_6-6_internal_loop-symmetric_GAUUAG-GCCCGG; 5_1-1 mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-UCGGGA

1583
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 53_3-3_bulge-

symmetric_AUG-GCG; 70_3-3_bulge-symmetric_UCA-AUU

815
-7_6-6_internal_loop-symmetric_GUUCAG-GCCCCG; 3_1-1_mismatch_A-C;

34_6-6_internal_loop-symmetric_GAUUUG-GCCUGG

1576
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC; 49_4-4_bulge-

symmetric_UGUG-GUAU; 63_4-4_bulge-symmetric_AGAU-UGGC

1051
-5_6-6_internal_loop-symmetric_UCAGAG-AGAUAC; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CGCCCC

1411
-2_6-6_internal_loop-symmetric_GAGAUA-AGCGGG; 5_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-CCUCCC

24
5_1-1 mismatch_A-C; 23_6-6_internal_loop-symmetric_AUCCUA-CGUCCG

1163
-4_6-6_internal_loop-symmetric_CAGAGA-AUGAGA; 3_1-1_mismatch_A-

C; 32_6-6_internal_loop-symmetric_AAGAUU-CCCAGC

935
-6_6-6_internal_loop-symmetric_UUCAGA-GGAACU; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CUGACC

680
-8_6-6_internal_loop-symmetric_AGUUCA-ACCCGA; 3_1-1 mismatch_A-C;

32_6-6_internal_loop-symmetric_AAGAUU-CUGGAC

1212
-4_6-6_internal_loop-symmetric_CAGAGA-GACAUU; 3_1-1_mismatch_A-

C; 42_6-6_internal_loop-symmetric_UCUUUU-UCGUCC

594
-9_6-6_internal_loop-symmetric_UAGUUC-UCUUGC; 3_1-1_mismatch_A-C;

40_6-6_internal_loop-symmetric_CAUCUU-CCUUCC

1185
-4_6-6_internal_loop-symmetric_CAGAGA-AAGGUC; 5_1-1_mismatch_A-

C; 36_6-6_internal_loop-symmetric_UUUGCA-GACCUC

1463
-1_6-6_internal_loop-symmetric_AGAUAU-UCCCUG; 4_1-1_mismatch_A-C;

32_6-6_internal_loop-symmetric_AAGAUU-CAGGGG

1058
-5_6-6_internal_loop-symmetric_UCAGAG-ACGCAC; 5_1-1_mismatch_A-C;

34_6-6_internal_loop-symmetric_GAUUUG-AUCGGG

810
-7_6-6_internal_loop-symmetric_GUUCAG-AGUUUA; 3_1-1_mismatch_A-

C; 33_6-6_internal_loop-symmetric_AGAUUU-CCUAUA

392
-10_6-6_internal_loop-symmetric_UUAGUU-UGUCUU; 5_1-1_mismatch_A-

C; 23_6-6_internal_loop-symmetric_AUCCUA-AUUAUG

1104
-5_6-6_internal_loop-symmetric_UCAGAG-GGGUCC; 3_1-1_mismatch_A-C;

44_6-6_internal_loop-symmetric_UUUUGU-UGCCCC

Example 11

Targeting of the DUX4 polyA Site in Cells

This example describes the change in expression of reporters fused to mutated DUX4-FL polyA site adenosines. To test the expression of the DUX4-FL polyA site in cells, two DUX4-FL fluorescent reporters were designed and generated. A GFP reporter construct (EF1a-GFP-DUX4flwt3′UTR) and a luciferase reporter construct (EF1a-luciferase-DUX4flwt3′UTR), were tested in immortalized myoblasts (LHCN-M2 cells, also known as LHCNs). A schematic of the luciferase and GFP constructs are shown in FIG. 7. Both reporters were engineered to include alternative versions where specific adenosine(s) at the polyA site were mutated to G to test their role in mRNA and protein levels. In addition to the unaltered version (or wild type version) ATTAAA, the alternate versions included ATTAAG; ATTAGA; ATTGAA; GTTAAA; and GTTGGG. To determine the RNA sequence of these polyA sites, all T bases are substituted with U bases. Given that if a said mutation(s) resulted in lower mRNA/protein levels, there would be less GFP/luciferase mRNA and protein in cells expressing mutant constructs.

To determine if mutations of the DUX4-FL polyA site in LHCN-M2 cells changed expression of the reporter, the cells were transfected with the luciferase construct. Immortalized LHCN muscle cells were forward plated at 10K cells/well and transfected the next day with 500 ng of DNA plasmid (Lipofectamine 2000, 1:3 DNA:reagent ratio). The cells were processed for viability and analyzed via a mCherry flow analysis. The supernatants were examined by a luciferase assay 48 hours post-transfections. Results from the luciferase experiment are shown in FIGS. 8A-8C. The cells were ˜80%-90% viable after the transfection and had transfection efficiencies of ˜7-40% (mCherry positive), as shown in FIG. 8A. The different transfection efficiencies may be due to the difficulties associated with transfecting muscle cells. The luciferase expression was normalized to mCherry median fluorescent intensity (MFI) (shown in FIG. 8B). As shown in FIG. 8C, after normalization, the constructs STX994 (ATTAGA), STX995 (ATTGAA), and STX997 (GTTGGG) resulted in significant downregulation of the WT DUX4-3′UTR luciferase signal STX992 (ATTAAA). STX993 (ATTAAG) resulted in a significant increase in luciferase signal, while STX996 (GTTAAA) showed no change. The “Un” was the untransfected control and “Exb296” was the positive control. These results indicate, DUX4 can be downregulated in a muscle cell by mutating the DUX4-FL polyA site.

To determine if mutations of the DUX4-FL polyA site in LHCN-M2 cells changed expression of the reporter, the cells were transfected with the GFP construct. Immortalized LHCN muscle cells were forward plated at 10K cells/well and transfected the next day with 250 ng of DNA plasmid (Lipofectamine 2000, 1:3 DNA:reagent ratio). The cells were processed for viability and analyzed via mCherry/GFP flow analysis 48 hours post-transfections. The results from the GFP experiment are shown in FIGS. 9A-9C. The cells were greater than 90% viable after the transfection and had transfection efficiencies of ˜10-40% (mCherry positive), as shown in FIG. 9A. The different transfection efficiencies may be due to the difficulties associated with transfecting muscle cells. The GFP MFI was normalized to mCherry MFI (shown in FIG. 9B). As shown in FIG. 9C, after normalization, all constructs, STX999 (ATTAAG), STX1000 (ATTAGA), STX1001 (ATTGAA), STX1002 (GTTAAA) and STX1003 (GTTGGG) resulted in significant downregulation of the WT DUX4-3′UTR GFP signal STX998 (ATTAAA). The “Un” was the untransfected control. These results indicate, DUX4 can be downregulated in a cell by mutating the DUX4-FL polyA site. These constructs (luciferase and GFP) can also be used with guide RNAs described herein to test expression changes resulting from RNA editing of the DUX4 polyA site.

Example 12

Targeting of the DUX4 polyA Signal Sequence in Cells

HEK cells were transfected with a DUX4-luciferase reporter that was stably integrated via the Piggybac system. The same DUX4-luciferase reporter was used for the ADAR 1/2 Knockout (KO) cells. To test editing of the DUX4 polyA site, seven gRNAs were tested and a no transfection control was tested. The seven gRNAs that were tested were SEQ ID NO: 8, SEQ ID NO: 593, SEQ ID NO: 934, SEQ ID NO: 977, SEQ ID NO: 1054, SEQ ID NO: 1294, and SEQ ID NO: 1463. Cells were transfected with a plasmid individually encoding each one of the seven gRNAs. The cells were collected 48 hours post transfection, and RNA was collected, converted to DNA by reverse transcriptase and sequenced via Sanger sequencing. FIG. 11 shows limited to no editing in the ADAR ½ knockout cells with the 7 guides tested. FIG. 10 shows the editing in HEK cells comprising a functional ADAR 1. For example, the SEQ ID NO: 8 guide facilitated high levels of editing (about 60%) at position 3 of the DUX 4 poly A tail, which is the third A from the 5′ end of ATTAAA. Editing with the SEQ ID NO: 593 guide had high levels of editing (about 70%) at positions 0 (the first A of ATTAAA), and position 3 of the DUX 4 poly A tail. Greater than 40% editing was also seen at positions 4, and 5 of the poly A tail with SEQ ID NO: 593, which is the third A and the fourth A from the 5′ end of ATTAAA, respectively. Editing with the SEQ ID NO: 934 guide had high levels of editing (about 78%) at position 0, about 75% editing at position 3, and about 60% editing at position 4 of the DUX 4 poly A tail. Editing with the SEQ ID NO: 977 guide had high levels of editing (about 75%) at position 3, and about 60% editing at positions 4 and 5. Editing with the SEQ ID NO: 1054 guide had high levels of editing (greater than about 70%) at positions 0 and 3, and about 40% editing at position 4. Editing with the SEQ ID NO: 1294 guide had high levels of editing (about 70% to 75%) at positions 3 and 4, and about 40% editing at position 0. Editing with the SEQ ID NO: 1463 guide had high levels of editing (about 80%) at positions 3 and 4. These results indicate that DUX-4 mRNA can be edited at a high efficiency in cells.

mRNA Knockdown. RNA preps (2 biological replicates) from cells used to quantify the above editing levels were also analyzed for mRNA knockdown by qPCR for mRNA knockdown. qPCR data was normalized to GAPDH mRNA and the average fold change of two biological replicates is presented in TABLE 4 below, with the no transfection control being set to 1. Knockdown was observed for all the engineered guide RNAs tested in the WT cell background, while ADAR ½ KO cells showed mostly no knock down.

TABLE 4

DUX4 mRNA Knockdown (Fold Change Normalized to GAPDH n = 2)

No
SEQ ID
SEQ ID
SEQ ID
SEQ ID
SEQ ID
SEQ ID
SEQ ID

Transfection
NO: 8
NO: 593
NO: 934
NO: 977
NO: 1054
NO: 1294
NO: 1463

WT
1.00
0.367
0.50085
0.42213
0.39594
0.2907
0.51247
0.70405

ADAR
1.00
0.82464
0.947
1.048593
0.8753
0.817242
0.734
0.853

½ KO

Example 13

Reduction of DUX4 mRNA Transcript

This example describes the reduction of DUX4 mRNA levels in cells. Human FSHD-derived myoblasts are transfected with any of the engineered guide RNAs described herein (e.g., any one of SEQ ID NO: 2-SEQ ID NO: 1589). The cells are samples at 0, 12, 24, and 48 hours after transfection. After sampling the cells, the cells are lysed and RNA is purified. The RNA is converted to DNA with a reverse transcriptase and RNA levels are determined by quantitative real time polymerase chain reaction (qRT-PCR). relative and absolute expression levels are determined for DUX4 mRNA levels. DUX4 mRNA levels decrease after transfection with the engineered guide RNA.

Example 14
Reduction of DUX4 Downstream Protein Level

This example describes the reduction of a protein downstream of DUX4. Human FSHD-derived myoblasts are transfected with any of the engineered guide RNAs described herein (e.g., any one of SEQ ID NO: 2-SEQ ID NO: 1589). The cells are samples at 0, 12, 24, and 48 hours after transfection. After sampling the cells, the cells are lysed and protein samples are prepared of the lysed cells. The protein samples are ran on a SDS-PAGE gel and transferred to a nitrocellulose blot. Protein levels are determined by a Western blot with a primary antibody directed to SLC34A2. Densitometry is used to determine the protein levels of SLC34A2. SLC34A2 protein levels decrease after transfection with the engineered guide RNA.

Example 15
Compositions for the Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD)

This example describes a vector for treatment of FSHD. A subject is diagnosed with FSHD, which is caused misexpression of the DUX4 gene. The subject is prescribed a dosing regimen of a pharmaceutical composition. The pharmaceutical composition comprises a vector comprising a engineered guide RNA described herein (e.g., SEQ ID NOs: 2-1589) that is directed to mutate a region in the polyA signal sequence (ATTAAA) of DUX4-FL. The pharmaceutical composition is administered systemically to the subject by intravenous administration in an effective amount to treat the FSHD disease.

While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein can be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Number	Date	Country
63303662	Jan 2022	US
63277665	Nov 2021	US
63216175	Jun 2021	US
63192818	May 2021	US

Engineered Guide RNAs and Polynucleotides

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