Claims
- 1. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 3′ splice region comprising a branch point, a pyrimidine tract and a 3′ splice acceptor site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 2. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 3′ splice acceptor site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 3. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 5′ splice site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 4. The modified synthetic nucleic acid molecule of claim 1 wherein the nucleic acid molecule further comprises a 5′ donor site.
- 5. The modified synthetic nucleic molecule of claim 1, 2, 3 or 4 further comprising a spacer region that separates the 3′ splice region from the target binding domain.
- 6. The modified synthetic nucleic acid molecule of claim 1, 2, 3, or 4 further comprising a safety sequence comprising one or more complementary sequences that bind to one or both sides of the 3′ splice site.
- 7. The modified synthetic nucleic acid molecule of claim 1, 2, 3, or 4 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 8. The modified synthetic nucleic acid molecule of claim 5 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 9. The modified synthetic nucleic acid molecule of claim 6 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 10. The modified synthetic nucleic acid molecule of claim 1, 2, 3 or 4 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 11. The modified synthetic nucleic acid molecule of claim 5 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 12. The nucleic acid molecule of claim 6 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 13. The modified synthetic nucleic acid molecule of claim 1, 2, 3 or 4 wherein the nucleotide sequence to be trans-spliced to the target pre-mRNA contains a nonsense mutation.
- 14. The modified synthetic nucleic acid molecule of claim 5 wherein the nucleotide sequence to be trans-spliced to the target pre-mRNA contains a nonsense mutation.
- 15. The modified synthetic nucleic acid molecule of claim 6 wherein the nucleotide sequence to be trans-spliced to the target pre-mRNA contains a nonsense mutation.
- 16. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 3′ splice region comprising a branch point, a pyrimidine tract and a 3′ splice acceptor site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 17. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 3′ splice acceptor site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 18. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 5′ splice site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 19. The modified synthetic nucleic acid molecule of claim 16 wherein the nucleic acid molecule further comprises a 5′ donor site.
- 20. The modified synthetic nucleic molecule of claim 16, 17, 18 or 19 further comprising a spacer region that separates the 3′ splice region from the target binding domain.
- 21. The modified synthetic nucleic acid molecule of claim 16, 17, 18 or 19 further comprising a safety sequence comprising one or more complementary sequences that bind to one or both sides of the 3′ splice site.
- 22. The modified synthetic nucleic acid molecule of claim 16, 17, 18 or 19 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 23. The modified synthetic nucleic acid molecule of claim 20 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 24. The modified synthetic nucleic acid molecule of claim 21 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 25. The modified synthetic nucleic acid molecule of claim 16, 17, 18 or 19 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 26. The modified synthetic nucleic acid molecule of claim 20 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 27. The nucleic acid molecule of claim 21 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 28. The modified synthetic nucleic acid molecule of claim 16, 17, 18 or 19 wherein the nucleotide sequence to be trans-spliced to the target pre-mRNA contains a nonsense mutation.
- 29. The modified synthetic nucleic acid molecule of claim 20 wherein the nucleotide sequence to be trans-spliced to the target pre-mRNA contains a nonsense mutation.
- 30. The modified synthetic nucleic acid molecule of claim 21 wherein the nucleotide sequence to be trans-spliced to the target pre-mRNA contains a nonsense mutation.
- 31. The nucleic acid molecule of claim 1, 2, 3,4, 5,6, 16, 17, 18, 19, 20 or 21 further comprising a nuclear localization signal.
- 32. The nucleic acid molecule of claim 1, 2, 3, 4, 5, 6, 16, 17, 18, 19, 20 or 21 wherein said nucleic acid molecule is a circular molecule.
- 33. The nucleic acid molecule of claim 1, 2, 3, 4, 5, 6, 16, 17, 18, 19, 20 or 21 further comprising an enhancer sequence.
- 34. A composition comprising a physiological acceptable carrier and a nucleic acid molecule according to claim 1, 2, 3, 4, 5, 6, 16, 17, 18, 19, 20 or 21.
- 35. A composition comprising a physiological acceptable carrier and a nucleic acid molecule according to claim 1, 2, 3, 4, 5, 6, 16, 17, 18, 19, 20 or 21.
- 36. An expression vector comprising an RNA polymerase promoter and a nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 3′ splice region comprising a branch point, a pyrimidine tract and a 3′ splice acceptor site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 37. An expression vector comprising an RNA polymerase promoter and a nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 3′ splice acceptor site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 38. An expression vector comprising an RNA polymerase promoter and a nucleic acid molecule comprising:
a) one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within the cell; b) a 5′ splice site; and c) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 39. The expression vector of claim 36 wherein the nucleic acid molecule further comprises a 5′ donor site.
- 40. The expression vector of claim 36, 37, 38 or 39 further comprising a spacer region that separates the 3′ splice region from the target binding domain.
- 41. The expression vector of claim 36, 37, 38 or 39 further comprising a safety sequence comprising one or more complementary sequences that bind to one or both sides of the 3′ splice site.
- 42. The expression vector of claim 36, 37, 38 or 39 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 43. The expression vector of claim 40 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 44. The expression vector of claim 41 wherein the binding of the nucleic acid molecule to the target pre-mRNA is mediated by complementary, triple helix formation, or protein-nucleic acid interaction.
- 45. The expression vector of claim 36, 37, 38 or 39 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 46. The expression vector of claim 40 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 47. The expression vector of claim 41 wherein the nucleotide to be trans-spliced to the target pre-mRNA encodes a translatable polypeptide.
- 48. A method for synthesizing the nucleic acid molecule of claim 1, 2, 3, 4, 5 or 6 wherein said nucleic acid molecule is chemically synthesized.
- 49. A method for synthesizing the nucleic acid molecule of claim 1, 2, 3, 4, or 5 wherein said nucleic acid molecule is synthesized in vitro.
- 50. A modified synthetic nucleic acid molecule wherein said modification enhances the stability of the nucleic acid molecule comprising:
a)one or more target binding domains that target binding of the nucleic acid molecule to a pre-mRNA expressed within a cell; b) a 5′ donor site; c) a 3′ splice acceptor site; d) a nucleotide sequence to be trans-spliced to the target pre-mRNA; wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell.
- 51. The modified synthetic nucleic acid molecule of claim 50 further comprising a spacer region that separates the 3′ splice region from the target binding domain.
- 52. The modified synthetic nucleic acid molecule of claim 50 further comprising a safety sequence comprising one or more complementary sequences that bind one or both sides of the 3′ splice site.
- 53. The nucleic acid molecule according to claim 1, 2, 3, 4, 5, 6, 16, 17, 18, 19, 20 or 21 associated with a liposome.
Parent Case Info
[0001] The present application is a continuation-in-part of a pending application Ser. No. 09/838,858 filed on Apr. 20, 2001 which 09/941,492 filed on Aug. 29, 2001 which is a continuation-in-part of a pending application Ser. No. 09/838,858 filed on Apr. 20, 2001 which is a continuation-in-part of pending application Ser. No. 09/756,096 filed Jan. 8, 2001 which is a continuation-in-part of pending application Ser. No. 09/158,863 filed Sep. 23, 1998 which is a continuation-in-part of Ser. No. 09/133,717 filed on Aug. 13, 1998 which is a continuation-in-part of Ser. No. 09/087,233 filed on May 28, 1998, which is a continuation-in-part of pending application Ser. No. 08/766,354 filed on December 13, 1996, which claims benefit to provisional application No. 60/008,317 filed on Dec. 15, 1995.
Government Interests
[0002] The present invention was made with government support under Grant Nos. The present invention was made with government support under Grant Nos. SBIR R43DK56526-01 and SBIR5R44DK56526-03. The government has certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60008317 |
Dec 1995 |
US |
Continuation in Parts (7)
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Number |
Date |
Country |
Parent |
09941492 |
Aug 2001 |
US |
Child |
10076248 |
Feb 2002 |
US |
Parent |
09838858 |
Apr 2001 |
US |
Child |
09941492 |
Aug 2001 |
US |
Parent |
09756096 |
Jan 2001 |
US |
Child |
09838858 |
Apr 2001 |
US |
Parent |
09158863 |
Sep 1998 |
US |
Child |
09756096 |
Jan 2001 |
US |
Parent |
09133717 |
Aug 1998 |
US |
Child |
09158863 |
Sep 1998 |
US |
Parent |
09087233 |
May 1998 |
US |
Child |
09133717 |
Aug 1998 |
US |
Parent |
08766354 |
Dec 1996 |
US |
Child |
09087233 |
May 1998 |
US |