AAV NATIVE-NEURO PLATFORM AND USE FOR NEURONAL DISEASE GENE THERAPY

BACKGROUND OF THE INVENTION

Gene-based neurotherapeutics holds great therapeutic potential. Clinical efficacy has already been obtained for central nervous system (CNS) diseases and eye disease through Adeno Associated Virus (AAV) gene therapy. The general lack of current effective neurotherapies for many devastating neurologic diseases portends great future demands for AAV gene-based neurotherapy.

Efficient and specific delivery to a target organ, such as the brain, is a rate limiting step in many protein-based therapeutics. There are multiple barriers to efficient direct protein delivery to the CNS.

One of the great challenges lies in the blood-brain barrier (BBB). Unlike the vasculature in other organ systems, the brain endothelium forms intercellular tight junctions (TJs) that limit greatly the paracellular access of blood-borne components to the tissue parenchyma. As a consequence of this “physical barrier” generated by TJs, gene transfer vehicles attempting entry into the CNS are forced to go through the transcellular route. There, however, specialized lumen facing efflux transporters, which include both the ABC family of transporters and multidrug resistance-related proteins, contribute to the formation of the “transport barrier” that prevents xenobiotic substances from gaining access to the neuronal environment. Another obstacle that partially prevents endothelial crossing of gene-therapy vehicles is the trancytotic/endosomal sorting, which can lead to degradation. Although the endothelium is the greatest obstacle in restricting access to the CNS, the presence of a complex extracellular space, molecular composition and geometry also significantly impede diffusion of viral-based gene delivery systems. That is, even if a therapy can be designed to target one of these receptors and traverse the BMVEC cytoplasm to be released at the basal cell membrane, only the first of many guardian mechanisms at the BBB has been overcome. If neurons are the target cell type, once the BBB endothelium has been passed, the basal lamina, pericytes, microglial ramifications, and the glial limitans comprised of astrocytic endfeet still have to be navigated before surpassing all of the checkpoints at the BBB and encountering a neuron.

As a result, intravascular administration of most viral vectors with the exception of few AAV serotypes has proven unsuccessful in the treatment of neurological diseases, potentially because these gene delivery platforms cannot negotiate their way across the BBB to access their target cells.

Another challenge lies in the promoters used in the gene therapy vectors. With the discovery of new viral vectors, mainly AAV capsids, with remarkable CNS tropism after vascular, CSF administration, or direct intracranial injection, the field of AAV mediated CNS gene therapy is accelerating rapidly towards clinical trials in a number of neurological diseases, and the expedient approach has been to use specific promoters with a proven track record of mediating long-term gene expression given the serious nature of many of these diseases, many of which are pediatric.

The majority of the pre-clinical studies have used strong ubiquitous promoters to provide a broad overview of transgene expression in different tissues and cell types throughout the body after intravascular infusions, or CNS cell types after intracranial delivery.

The CAG/CBA/CB promoter is generally viewed as a ubiquitous promoter as it works in numerous tissues and cell types. However, the assumption that it is highly active in every cell type may not be entirely warranted in the CNS. Studies have been conducted using AAV vectors with the same capsid but carrying different CNS cell specific promoters or the CBA promoter. The apparent discrepancy in CNS transduction profiles of these different AAV vectors suggests that the CBA promoter may not mediate detectable transgene expression in all cell types in the brain. Additional experiments have been conducted using AAV vectors with numerous tropism carrying the cytomegalovirus (CMV), CBA, Rous sarcoma virus (RSV), or human GUSB promoters to drive transgene expression, in the context of intra-parenchymal delivery to different brain structures.

In clinical studies, the majority of AAV vectors for treating neurological diseases have used the CMV immediate early promoter followed by a chimeric intron composed of a CMV splice donor and a human globin splice acceptor, or a version of the CAG/CBA promoter (supra). Two other clinical trials have tested AAV vectors carrying mammalian promoters such as the mouse phosphoglycerate kinase (PGK) promoter, or the rat neuron-specific enolase (NSE) promoter. The choice of promoters is based on the availability of extensive data from pre-clinical studies in different animal models showing that AAV-mediated transgene expression under these promoters is stable and long lasting in the mammalian brain. The stability of AAV gene expression in the human brain has been evaluated in clinical trials using an AAV2 vector encoding aromatic amino acid decarboxylase (AADC) injected into the putamen of Parkinson's disease patients, or children afflicted with AADC deficiency.

An indisputable fact about these AAV-CMV or AAV-CAG/CBA vectors is their ability to drive strong gene expression in many neurons in the CNS of multiple species. The disparate CNS transduction results between cellular promoters and strong non-mammalian promoters raises the possibility that the current generation of AAV vectors express transgenes at exceptionally high levels in a small percentage of all cells that harbor transcriptionally ready vector genomes in the nucleus. A recent report documented considerable toxicity in non-human primates (NHPs) receiving intraparenchymal injections of an AAV2 vector encoding human acid sphingomyelinase. Another safety study on intracranial delivery of an AAVrh10 vector encoding human tripeptidyl peptidase (TPP-I) in NHPs reported white matter edema and inflammation. The interpretation of these results is complicated, but a possible interpretation of the results is that these inflammatory responses are secondary to protein expression overload and non-specific expression in AAV transduced neurons.

The potential for toxicity due to excessive transgene expression is particularly acute in neurological diseases where the expressed proteins are not secreted, and thus the need for high level expression is even less. In one particular case, the development of an AAV gene therapy approach for Rett syndrome represents a significant challenge to the prevalent approach of simply using strong promoters. This disease is caused by mutations in the MeCP2 gene on the X-chromosome. Interestingly, duplication of this gene also leads to neurodevelopmental delays, suggesting that expression of this gene in the CNS need to be tightly controlled, which is a challenge to current AAV gene therapy.

SUMMARY OF THE INVENTION

The invention described herein provides a gene replacement therapy platform to replace mutated genes by AAV Gene Therapy.

According to the invention described herein, about 40 exemplary central nervous system (CNS) disease drug protypes are packaged in recombinant AAV vectors for intravenous administration to a patient, in order to express functional genes in native neuronal cells. The technology is designed for intravenous dosing of AAV to express genes precisely in intended cell types by using endogenous/native promoter fused with viral/heterologous enhancer.

In an exemplary embodiment, the gene cassette in the AAV vector of the invention begins with AAV inverted terminal repeat (ITR), followed by proprietary heterologous enhancer, followed by a native promoter of a gene of interest (GOI), 5′UTR, proprietary codon optimized gene of interest (GOI), 3′UTR, and ends in another AAV inverted terminal repeat (ITR).

Thus one aspect of the invention provides a recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the transcriptional control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.

In certain embodiments, the GOI is a neuronal gene, or is a gene expressed in neuronal tissues (CNS and/or PNS).

In certain embodiments, the GOI is defective (e.g., loss-of-function) in a neuronal disease or condition.

In certain embodiments, the neuronal disease or condition is a CNS disease or condition.

In certain embodiments, the CNS disease or condition is: Ceroid-Lipofuscinosis, Fucosidosis, Giant Axonal Neuropathy, Globoid cell leukodystrophy, Mucolipidiosis Type IV, Neuronal Ceroid Lipofusinoses, Niemann-Pick Disease, Sandhoff Disease, Sanfilippo syndrome, Tay-Sachs Disease, Hunter Syndrome, Sialidosis, Multiple Sulfatase Deficiency, Childhood Epilepsy, CMT Peripheral Neuropathy, Neuronal Ceroid Lipofusinoses, Aspartylglycosaminuria, Mucopolysaccharidoses, Parkinsons Disease/Symptoms, GM1-Gangliosidosis, Charcot-Marie-Tooth Type 1A, Retts Syndrome, Dannon Disease, Mucopolysaccharidoses (due to GNS, HGSNAT, NAGLU, or ARSB), Sly Syndrome, Biotin basal ganglia disease, Pelizaeus-Merzbacher disease, Neuronal Ceroid Lipofusinoses, Canavan Disease, Beta-Mannosidosis, Wolman Disease, Cystinosis, Alzheimer's Disease/Symptom, Salla Disease, Jansky-Bielschowsky disease, Neuronal ceroid lipofuscinoses, or GM2 gangliosidosis.

In certain embodiments, the GOI is: CLN3, FUCA1, GAN, GALC, MCOLN1, PPT1, SMPD1, HEXB, SGSH, HEXA, IDS, NEU1, SUMF1, GAT1/SLCA1, FIG. 4, CLN5, AGA, IDUA, GDNF, GLB1, PMP22/MFN2, MECP2, LAMP2, NAGLU, ARSB, GUSB, SLC19A3, PLP1, TPP1/CLN2, ACY2/ASPA, MANBA, LIPA, CTNS, GNS, HGSNAT, NEUROD1, SLC17A5, CLN6, CLN8, or GM2A.

In certain embodiments, the rAAV has a tropism for neuronal cells, or for a cell in neuronal tissue.

In certain embodiments, the rAAV is AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10, preferably AAV9.

In certain embodiments, the rAAV comprises AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10 capsids, preferably AAV9 capsids.

In certain embodiments, the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.

In certain embodiments, the heterologous enhancer is a viral enhancer.

In certain embodiments, the viral enhancer is CMV enhancer.

In certain embodiments, the viral enhancer is SV-40 enhancer.

In certain embodiments, the heterologous enhancer comprises a polynucleotide of SEQ ID NO: 1.

Another aspect of the invention provides a pharmaceutical composition comprising any one of the rAAV vector of the invention.

In certain embodiments, the pharmaceutical composition is formulated for intravenous administration (e.g., to the blood) or intrathecal administration (e.g., to spinal fluid).

Another aspect of the invention provides a cell infected with any one of the rAAV vector of the invention.

Another aspect of the invention provides a recombinant AAV virus comprising any one of the rAAV vector of the invention, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell or a cell in neuronal tissue.

Another aspect of the invention provides a method of treating a (genetic) disease or disorder in a subject, the method comprising administering the recombinant AAV virus of the invention into the subject.

In certain embodiments, the genetic disease or disorder is a neuronal disease or disorder, and/or wherein the recombinant AAV virus preferentially infects a neuronal cell or a cell in neuronal tissue of the subject, thereby treating the neuronal disease or disorder.

In certain embodiments, the rAAV virus is administered to the subject intravenously or intrathecally.

Another aspect of the invention provides a method of producing any one of the rAAV vector of the invention, the method comprising introducing any one of the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.

In certain embodiments, the rep/cap proteins comprise one or more AAV9 capsid proteins.

It should be understood that any one embodiment of any one of the aspects of the invention above, including specific embodiments described only in one section of the application, can be combined with one or more additional embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing (not to scale) showing a generic structure of the subject rAAV vector, as well as an intended mode of action for the vector. The Gene of Interest (GOI) is put under the control of its native promoter. Transcription from the native promoter is further enhanced by the presence of a powerful enhancer, such as a viral enhancer like CMV enhancer, to facilitate the expression of the GOI in the native cells such GOI is normally expressed. The entire recombinant sequence is flanked by two AAV ITR sequences, such as AAV9 ITR sequences for the preferred neuronal cell tropism.

FIG. 2 is a gel image confirming the construction of rAAV viral vectors comprising a number of representative GOI's that are defective in neuronal diseases/disorders. Also shown is a rAAV vector encoding a GFP reporter gene, which can be switched out by any of the GOI's.

FIG. 3 is a gel image confirming the construction of additional rAAV viral vectors comprising a number of representative GOI' s that are defective in neuronal diseases/disorders.

DETAILED DESCRIPTION OF THE INVENTION
1. Overview

The invention described herein provides methods and compositions for using recombinant viral vectors, such as AAV-based viral vectors or lentiviral vectors to express any gene-of-interest (GOI) under the control of its native promoter so that the GOI is preferentially and exclusively expressed in the cells the GOI is intended to be expressed. The GOI is further under the transcriptional control of a powerful heterologous enhancer, such as a viral enhancer like CMV enhancer, which further boosts the transcription and expression of the GOI. Therefore, after a single intravenous treatment, the protein product of interest is expressed at high levels only in the endogenous/native cell types, thereby improving therapeutic safety and efficacy.

Thus in one aspect, the invention described herein provides a recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.

In certain embodiments, the GOI is a neuronal gene.

In certain embodiments, the neuronal gene is defective (e.g., loss-of-function) in a neuronal disease or condition.

In certain embodiments, the neuronal disease or condition is a CNS disease or condition.

In certain embodiments, the rAAV has a tropism for neuronal cells. In certain embodiment, the rAAV serotype is, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10.

In certain embodiments, the rAAV serotype is AAV9. In certain embodiments, the rAAV has a pseudotype of xxx. In certain embodiments, the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.

In certain embodiments, the heterologous enhancer is a viral enhancer.

In certain embodiments, the viral enhancer is CMV enhancer.

In certain embodiments, the viral enhancer is SV40 enhancer.

Another aspect of the invention provides a pharmaceutical composition comprising the rAAV vector of the invention.

In certain embodiments, the pharmaceutical composition is formulated for intravenous administration.

Another aspect of the invention provides a cell infected with the rAAV vector of the invention.

Another aspect of the invention provides a recombinant AAV virus comprising the rAAV vector of the invention, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell.

Another aspect of the invention provides a method of treating a (genetic) disease or disorder in a subject, the method comprising introducing the recombinant AAV virus of the invention into the subject.

In certain embodiments, the genetic disease or disorder is a neuronal disease or disorder, the recombinant AAV virus preferentially infects a neuronal cell of the subject, and treats the neuronal disease or disorder.

Another aspect of the invention provides a method of producing the rAAV vector of the invention, comprising introducing the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.

With the general aspects of the invention described, further detailed embodiments of the invention are provided below.

2. Treatable Disease or Conditions

The recombinant AAV vector and recombinant AAV virus of the invention, together with the pharmaceutical composition comprising the same, can be used to treat a number of diseases and conditions, particularly neuronal diseases or indications treatable by gene therapy.

Diseases or conditions treatable by the AAV vector/virus/method of the invention are typically characterized by lacking a functional neuronal protein or enzyme, which neuronal diseases or indications can be alleviated (if not cured), treated, or prevented (e.g., at least the onset is delayed), by providing functional versions of the proteins or enzymes. The externally provided functional versions of the proteins or enzymes may be identical in sequence to the wild-type proteins or enzymes that are lacking in a host having such diseases or conditions, or may be a variant of the wild-type proteins or enzymes.

In certain embodiments, the neuronal diseases or conditions can be treated by introducing into the host the subject AAV virus that will infect target host (neuronal) tissues, and stably express the encoded GOI that is defective in the diseases or conditions throughout the life span of the host. The subject AAV virus may only need to be introduced into the host once, or can be introduced into the host multiple times as needed.

A few representative polynucleotide sequences of the invention encoding several genes-of-interest (GOI) are listed below. These polynucleotide sequences can be part of the subject AAV vector sequences. These sequences are for illustrative purpose only and are non-limiting.

Giant Axonal Neuropathy (GAN)

Giant axonal neuropathy (GAN) is a severe, slowly progressive neurodegenerative disorder characterized by progressive motor and sensory peripheral neuropathy, central nervous system involvement (including pyramidal and cerebellar signs), and characteristic kinky hair in most cases. GAN is inherited as an autosomal recessive trait, and is associated with more than 50 different causative mutations in GAN gene (16q24.1), encoding the ubiquitously expressed cytoskeletal protein gigaxonin.

Disease prognosis varies but is usually poor. Most patients become wheelchair-dependent in the second decade of life, and eventually progress to a bedridden state in early adulthood. Secondary complications, such as respiratory failure, may occur. Life expectancy does not exceed the third decade.

Current GAN treatment is symptomatic, focusing on stimulating intellectual and physical development, as well as communication skills, through physical, occupational and speech therapy, starting from the initiation of symptoms. Skeletal deformities and ophthalmoplegia may need surgery.

Thus in one embodiment, the GOI is GAN that encodes gigaxonin, and the disease or condition treatable by the subject AAV vector/virus is Giant Axonal Neuropathy (GAN). The composition and methods of the invention can be used to produce gigaxonin expressed permanently from AAV vectors stably maintained with the host's genome as extra chromosomal material, in native neuronal cells that normally express GAN, thus effectively treating giant axonal neuropathy.

A representative polynucleotide of the invention that can be encoded by the AAV vector of the invention is described below.

(SEQ ID NO: 2)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

CTCACAGGGATACTGGGTAGGTATCATGGAGAAGA

TAAGTCCAAGCTGCTTGTCTTGTGTGTTTCTTACC

TTTTTAAATATATTTTTCGGCCGGGTGTGGTGGCT

TATGCCTGTAATTCCAGTACTTTGGGAAGCCAAGG

TGGGCGGATCACAAGGTCAGGAGTTCGATACCAGC

CTGGCCAACATGGTAAAACCCCATCTCTACTAAAG

ATGCAAAAGTTAGCCAGGCATGGTGGCACATGCCT

GTAGTCCCAGCTACTTGGGAGGCTGAGGCAGGAGA

ACCACTTGAACCCGGGAGGCGGAGGTTGCAGTGAA

CAGAGATTGCACAACTGCACTCCAGCCTGGGCAAT

AGAGGGAGACTCCATCTCAAAAAAAAAAAAGAAAG

AAGAAAATATTTTTCAACATCCACAAAAATATAGA

AACAGTACAATGAATCTCCACATCCCCATTAAACA

TCCACAACAATATAGAGACAGTACAACGAATCTCC

ACATCCCCATTACGTGGCTTTAACAATTAGTAACT

TGCGGCCACTTTTGACTCATCTACACTCCCATCTG

CTTCCCCATCCCTTTGTTTTGTTTTGAAGCAAATC

CTAGACATCTTTATCATTGCATCCGGGAACACTGA

GCTGCATTTACAGAAGAAAGTGGAAATGCATGTGT

CTTCCACAGCCGTACCCTCCCCATCTATTCTGCCC

TGAAAACAGTTAGATACTCGGATTCCTGCCAGTGA

CTCCAAAGCCTTGGCTGGTTCAGGGTAAATACCCA

AGACTTTATTGGAGCCTTTCAGTTGGTTGAAGGAC

AGTGAAAATTCCATCCTGTCTTGCCTGGAATGCTA

GCCACATTCTTCTGGTCCGGAGTCCTCATACAATT

GCTAATTTTTTAGAGGCTTATGGAGTCCCTAACGT

TTGCACAAAATGGTTGCTACATTCCACACTCCCAT

GTGCCCTGAGCAACCTCCAGGGAAACTTCAGATAC

CGTGGGGCTTGGCCTGCCAGCTGAGCTGACCCAGC

GATCCTTTCTATCACAGCTTTGATCTTCACTGGGT

TGGGAGCCTGTCTGAATCTAAACATCTGCCTCTCT

ACTGCCCACCCCTTCAGCATTTCCTAGCTCTCCCT

GAAAGGTGCAAACATGCATGCAGTTACTCAAACAG

AATATTTATCCTTAACTCCCTCTCCCTCACAATTT

CTTTTAAAACAATCCACTATTGTCTACCCCCGCCC

CCGCATCACCCTTTCATCCAGGTGCCCATTCCCTT

CTCTCTAGTCCTGCAATACCTAAGCATCGATCTGC

CTTTAGCACATCCATCCCCGCCTTATTCTCCACGC

AGGAGCTGAGTGACCTGCACAAAATCCCCTGCTAA

ATACGGTACTTCCATGGTTCTTCACCACTGCAGAA

ACCAAACTCCTTCCCACACCAAGGAGGCCCTGCAA

AATTTAAGGCCTCCTTCGGACTTCTCCAGCTTCAT

CTGCTACATCTCCTTCCTAGCCCGCAACCAAAACC

ATCTTTTCCGGGTCTGTTTTCTCGGGTTTTTGTCC

TCTCACCTGGGCAGCTCCTTTTCTCTCATAAATAA

AGAAAGCTACAGCGACTTCGCCCTTGCTTCCATGC

ATCATCTCATGAGTCCACAACAACACTAAGAATTC

GCTTTCATTTTGCAGACGGAGAAACTGAGGATGGG

CACCTTACCCATGGCCACAGAGCTAGTAAGTGGAA

CAGCTGCAACCAGGATTCAAACTCGCGGCTCCAGA

GGCCACAGGCTTAACCACGGAATCCTAGCCCGCCC

GCACATCCCTCCATCGCGGGAGCGACCTATCTCAT

CCGTAGACACCTTCCGCTGCACCCAGCCGCAGCTG

GTCAGGCGGGCGGAGGAAGGAGGCTTCTGATTGGC

CATCTCCAGCAGCGGAGGCGAGAAGGCGGGGAGCG

ACGGTGCGGGGGCGTCGCGGAGAAATGACTTCATG

ACGCGGCTTCTTAAAGGCGCCGGCCCAGCGCGCCG

CGGA

custom-character

ATGGCTGAGGGAAGTGCGGTCTCAGACCCCCAACA

CGCTGCAAGACTTCTGCGAGCTCTCTCATCTTTCA

GAGAGGAGTCACGCTTCTGTGACGCACACTTGGTC

CTTGACGGAGAAGAGATACCTGTCCAGAAAAATAT

ACTTGCCGCTGCATCCCCATACATTCGCACCAAGC

TGAACTACAATCCCCCTAAAGACGACGGGAGCACC

TATAAAATCGAATTGGAGGGCATCTCCGTGATGGT

AATGCGAGAGATACTGGATTACATATTTAGCGGCC

AGATCAGGCTGAATGAGGATACGATCCAAGATGTT

GTACAGGCAGCGGACTTGCTGCTTCTGACGGACCT

TAAGACCCTTTGCTGCGAGTTCCTCGAAGGGTGTA

TTGCTGCCGAGAATTGTATCGGAATACGAGACTTC

GCACTCCATTACTGCCTTCACCACGTTCATTACCT

TGCGACAGAGTATTTGGAAACACATTTCCGCGACG

TTAGCTCTACAGAGGAATTTCTCGAACTTAGTCCT

CAAAAGCTCAAGGAGGTTATTAGTCTTGAAAAGCT

CAACGTCGGAAATGAGCGGTACGTGTTTGAGGCCG

TGATACGGTGGATCGCCCACGACACCGAGATCCGC

AAGGTCCACATGAAGGATGTAATGTCAGCGCTGTG

GGTATCCGGTCTTGACTCTTCATACTTGAGAGAGC

AGATGCTCAACGAACCTTTGGTGAGGGAAATAGTG

AAGGAGTGTAGTAACATCCCCCTCAGCCAACCCCA

GCAAGGCGAAGCGATGCTCGCGAACTTCAAGCCCC

GAGGCTACAGCGAATGCATAGTAACAGTGGGAGGT

GAAGAACGGGTCTCCCGGAAACCCACTGCGGCGAT

GCGGTGTATGTGTCCCCTGTATGATCCCAATCGCC

AACTTTGGATCGAGCTGGCGCCGCTGTCTATGCCA

CGAATAAATCACGGGGTTCTTTCAGCCGAGGGGTT

TCTGTTCGTCTTTGGAGGGCAGGATGAGAACAAAC

AAACACTCTCCAGTGGGGAGAAATACGACCCCGAT

GCAAACACTTGGACAGCTCTGCCACCGATGAACGA

AGCCCGACACAACTTTGGTATAGTCGAAATCGACG

GTATGCTGTATATCCTTGGAGGAGAGGACGGAGAA

AAAGAACTCATCTCCATGGAATGTTACGACATTTA

CAGCAAAACTTGGACAAAGCAACCCGACCTTACTA

TGGTGAGGAAGATAGGATGTTATGCGGCAATGAAG

AAAAAGATATACGCCATGGGAGGCGGTTCTTATGG

TAAGCTCTTCGAGAGTGTGGAGTGTTATGACCCTC

GAACGCAGCAATGGACAGCCATATGTCCCCTGAAG

GAACGGCGATTTGGGGCGGTAGCGTGTGGAGTTGC

AATGGAGTTGTACGTTTTCGGAGGTGTTCGAAGTC

GGGAGGACGCGCAAGGGTCAGAGATGGTCACATGT

AAAAGCGAATTTTATCATGACGAATTTAAGCGGTG

GATTTATCTGAACGACCAAAACCTCTGTATTCCAG

CTTCCAGTTCCTTCGTATACGGCGCTGTGCCAATA

GGTGCGTCAATTTACGTCATAGGCGACTTGGACAC

TGGTACTAATTATGATTACGTACGCGAGTTTAAGA

GGAGTACAGGCACCTGGCACCACACAAAACCGCTG

CTCCCGTCCGATCTGCGAAGGACAGGTTGCGCTGC

ATTGAGGATTGCTAACTGCAAACTTTTCCGCCTGC

AACTTCAGCAAGGGCTTTTCCGCATACGAGTCCAC

AGTCCTGACTATAAAGATGACGACGACAAATA

custom-character

In the sequence herein, double underlined sequences represent proprietary viral enhancer sequences (SEQ ID NO: 1, see below); bold sequences are native promoter sequences for GAN; italic sequences are coding sequence for the GOI (GAN in this case); the subscripted sequences immediately 5′ and 3′ to the GOI coding sequence are 5′-UTR and 3′-UTR sequences, respectively.

The proprietary enhancer sequences (SEQ ID NO: 1) is listed below.

(SEQ ID NO: 1)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGT

ACCTTCTGAGGCGGAAAGAACCAGCGTTACATAACTTACGGTAAATGGCC

CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACG

TATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGT

GGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATA

TGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGG

CATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

The GAN protein sequence is:

(SEQ ID NO: 3)

MAEGSAVSDPQHAARLLRALSSFREESRFCDAHLVLDGEEIPVQKNILAA

ASPYIRTKLNYNPPKDDGSTYKIELEGISVMVMREILDYIFSGQIRLNED

TIQDVVQAADLLLLTDLKTLCCEFLEGCIAAENCIGIRDFALHYCLHHVH

YLATEYLETHFRDVSSTEEFLELSPQKLKEVISLEKLNVGNERYVFEAVI

RWIAHDTEIRKVHMKDVMSALWVSGLDSSYLREQMLNEPLVREIVKECSN

IPLSQPQQGEAMLANFKPRGYSECIVTVGGEERVSRKPTAAMRCMCPLYD

PNRQLWIELAPLSMPRINHGVLSAEGFLFVFGGQDENKQTLSSGEKYDPD

ANTWTALPPMNEARHNFGIVEIDGMLYILGGEDGEKELISMECYDIYSKT

WTKQPDLTMVRKIGCYAAMKKKIYAMGGGSYGKLFESVECYDPRTQQWTA

ICPLKERRFGAVACGVAMELYVFGGVRSREDAQGSEMVTCKSEFYHDEFK

RWIYLNDQNLCIPASSSFVYGAVPIGASIYVIGDLDTGTNYDYVREFKRS

TGTWHHTKPLLPSDLRRTGCAALRIANCKLFRLQLQQGLFRIRVHSPDYK

DDDDK

Conservative changes to the protein sequence above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 conservative residue changes, or up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% conservative residue changes) that result in a functional equivalent version of the protein (e.g., that retains at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% of the wild-type enzyme activity) are also within the scope of the invention.

Likewise, in any of the nucleotide sequence encoding the protein and variants thereof, such as in SEQ ID NO: 2, nucleotide sequence changes that do not result in sequence change of the encoded protein in SEQ ID NO: 3 due to, for example, codon degeneracy, are within the scope of the invention. Further, codon optimization of any of the polynucleotide sequence for optimal expression in a specific type of host cell is also within the scope of the invention (see further details below).

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL or Batten Disease)

Neuronal ceroid lipofuscinosis refers to a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) made up of fats and proteins in the body's tissues. The most commonly identified mutations are in the CLN3 gene, located on the short arm of chromosome 16 (16p12.1), found in childhood or juvenile NCLs (JNCLs).

JNCL is an autosomal recessive disorder. The normal function of CLN3 gene is not presently known, but it is known to be a transmembrane protein. Studies of the yeast CLN3 ortholog which encodes Battenin have suggested that the protein may play a role in lysosomal pH homeostasis. Furthermore, recent studies have also implied the protein's role in cathepsin D deficiency; the overexpression of the defective protein appears to have significant effects on cathepsin D processing, with implications suggesting that accumulation of ATP synthase subunit C would result.

All mutations resulting in JNCL have been shown to occur at the CLN3 gene. Of the mutations known to cause JNCL, 85% result from a 1.02 kb deletion, with a loss of amino acids 154-438, while the remaining 15% appear to result from either point or frameshift mutations.

Thus in one embodiment, the GOI is CLN3, and the disease or condition treatable by the subject AAV vector/virus is JNCL. The composition and methods of the invention can be used to produce CLN3 gene product expressed permanently from AAV vectors stably maintained with the host's genome as extra chromosomal material, in native neuronal cells that normally express CLN3, thus effectively treating JNCL.

A representative polynucleotide of the invention that can be encoded by the AAV vector of the invention is described below. Specifically, the proprietary enhancer sequence is in SEQ ID NO: 1. Native CLN3 promoter is known in the art. The coding sequence for CLN3 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN3-DNA

(SEQ ID NO: 4)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

TTCCCCCAGGGGCGGAAGGGGCCGGATTGGTGGCT

CTGGGGTGCATCCCCTCACCTATGATTAGGCTTGC

AAAAAAGAACTTGGCTAAACTTTATATTGTGGATA

TCTGTGTCTGCCTCCCACCTTCCTGTGACTTCCTT

GATGGCAGATGCCATGTATGAAACGCTGCTGAATT

TCTAGAGCCCTGCACGTTAGTAGGATTCCATTTTC

CATCAGCTGAGTGACCTGGGAGGCACACTAGAGAG

GGCACATTTCTTTTCTTTTCTTTTCTTTTTTTTTT

TGAGACAGTCTCACTCTGTCACCCAGGCTGGAGTG

TAGTGGCGCAGTCTCAGCTCACTGCAACCTCTGCC

TCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCC

CGAGTAGCTGGGATTACAGGTGCGTGCCACCACAC

CTGGTTAATTTTTGTATCTTTAGTAGAGACAGGGT

TTCACCATGTTAGCCAGGCTGGTTTCGAACTCCTG

ACCTCAGGTGATCTGCCCACCTTGGCCTCCCAAAG

TGCTGGGATGACAGGCATGAGCCACCACACCCAGA

CGAGAGGGCACATTTCCAACTGCATTCTGAAGGCC

TGGTGGTGAGAAAGAGCATATAGAGGTGGCACAGC

CCATAGCAGAGATGAGGCCAAGGACAAGAAGAGAA

TGCAGGATGCCGCTTTCCACCTAGAAGAAGGTAAG

GGTATGATTCCTTATTTGGAACTACATAAAGTGAC

CTTGCTCTACTTCTCTTCCCCATACCCTCCTTCTC

CCCTCCCCAGCCCCACTTTCCTATTCCAATTAGGG

CAATTCTATGAAATCACAGCATCAGAATCTTAGGC

CTTAAAATCATTTAGTCTGGCCAGGTGCAGTGGCT

CACGCCTGTAGTCCTAGCACTTTGGGAAGCCAAGG

CAGGTGGATTGCTTGAGCTCAGGAGTTTGAGGCCA

CCCTGGGCAACGTGGCAAAATCCAGTCTCTACAAA

AAACACAAAAATTAGCTGGGCACAGTGGTGCGCAC

CTGCTGTCCCAGCTACTCGGGAGGCTGAGGTGGGA

GGATCACCTGAGCCTGGGAGGTCAAGGTTGCAGCA

AACCAAGATCCTGCCACTGCACTCCAGCCTGGGCA

ACAGAGCAAAACCCTGTCAAAAAAAAAAAAAAAAT

CTGGTCTAAGCACCACCTTTGATGGAGGCAGGAAT

CCTGCAGCAGCCTGGAGCCAACCCAATGGCTCCCT

GCCTCTGGTGCTCTATTTCTTATCACCATACAGGT

CTCTAAGGTCACCTTTAGGTCTAACATTGTATGAA

TGATTGTCAGCAACTTTCCAATTTTTTTCATATAC

ATATATTTTTTTTATTTTATTTTTTACTTTTTCTT

TTTTTGAGACAGGATCTCACTCTGTCACCCAGGCT

GGAGTGCAGTGGCGTGATCATAGCTCACTGTAGCT

TCAACCTCCTGGGCACAAGTGATCCTCCCACCTCA

GCTTCCAAGGTACCTGTGACTACAGGAATGCGCCA

CCATGCCCGGCTAATTTTGTTATATATATATATAT

ATATATTTGTACCTTGGTTTTCTCATCTGTAACAC

CAGGGGTTGAAGTGCTGTGATATTTTTTGGTTCTA

GGATAATTTGGAAATAGGGATCTCTTAACATCTTG

GATACTGCCAATAGATCATTCACGAAATCCCTTTA

GATGAGTGTTATGTTTACTTAGGTCTCTAAAACAA

TTTGTAAGGTCAACAGATGGGGATAAGAATGACCT

GAAGCTGGTCGTCTTTGTTCGCAACCAGAAACAGT

CCTGCCTCAAAAAAAAAAAAAAAAAAAAGGGAGTA

GGCAGGTGGCCATATTTGTTTCTGGCAAGTGAGTG

CTGAAGGAAAGGAGCTGAAGCCTCCCACAGTCATA

ACTGGTGCTGGCAGGCTACTGTCTCGGTCTTGGGC

GCCACTGATCTAAGGTCACGGCTCTGCTTGCTGCT

CCCACCCGCTCCAGTTTAAAACCTGCGGTTCCAGG

GTTCTCCAGCCCCTCCCTTTTTCACGCTCCGAAGC

CGAGAAGGCCCAAAGCGAAGACAGAGAGGACCCGG

AAGTAGGGAAAACCTCTGAGCACGTGATGGGGGAA

CACGCGGGTGCTGT

custom-character

ATGGGAGGTTGTGCTGGTTCTCGACGCCGGTTCTC

AGATAGTGAGGGGGAGGAAACGGTGCCCGAGCCTC

GGCTTCCACTTCTGGACCATCAAGGCGCTCATTGG

AAGAATGCAGTCGGGTTTTGGCTCCTCGGTCTCTG

CAACAATTTCTCTTACGTGGTCATGTTGAGCGCTG

CCCATGACATTCTTAGTCATAAAAGAACCTCAGGC

AATCAGTCCCACGTTGATCCAGGTCCAACACCTAT

TCCTCATAACTCTAGCAGCAGATTTGACTGTAATA

GTGTTAGCACAGCTGCAGTGCTGCTCGCTGATATA

CTTCCGACGCTTGTTATAAAGTTGTTGGCTCCTCT

GGGATTGCACTTGCTGCCCTATAGTCCCCGAGTCT

TGGTTTCTGGCATTTGTGCTGCCGGCTCATTTGTC

TTGGTGGCTTTCAGTCACAGTGTGGGGACCAGTCT

GTGTGGAGTCGTGTTCGCATCAATTAGCTCTGGAC

TGGGCGAAGTAACCTTCCTGTCCCTCACAGCCTTT

TATCCGCGCGCCGTAATTAGTTGGTGGTCATCTGG

AACCGGCGGCGCGGGGCTGCTCGGCGCCCTTAGCT

ACCTGGGATTGACTCAGGCGGGGTTGTCACCACAA

CAGACTCTCCTTAGCATGCTTGGCATTCCAGCCTT

GCTTCTGGCTTCTTACTTTCTGCTCCTTACGTCCC

CGGAAGCGCAGGACCCTGGCGGTGAAGAGGAGGCG

GAGTCCGCCGCTCGACAGCCACTCATTCGAACTGA

AGCTCCCGAGTCCAAACCAGGAAGCTCTTCCTCCC

TCTCCCTGCGGGAACGGTGGACAGTCTTTAAGGGA

CTGCTGTGGTACATAGTGCCTCTTGTGGTAGTGTA

TTTCGCGGAATACTTCATAAACCAGGGTCTTTTTG

AGCTTCTTTTTTTTTGGAATACAAGCCTGTCACAC

GCCCAGCAGTACCGATGGTATCAGATGCTGTACCA

GGCGGGGGTTTTCGCTAGCCGATCCTCCCTGCGGT

GCTGCAGGATTCGATTCACTTGGGCTCTCGCGTTG

CTGCAATGCTTGAACCTCGTTTTCCTTCTCGCAGA

CGTCTGGTTCGGTTTTCTCCCTAGTATCTATCTGG

TCTTTTTGATTATATTGTATGAAGGTCTTCTGGGA

GGAGCGGCATACGTGAATACTTTTCACAATATCGC

CCTTGAGACTTCCGACGAGCATCGGGAATTTGCCA

TGGCGGCGACGTGTATCTCCGATACCCTGGGTATA

AGCCTGAGTGGACTGCTCGCGCTTCCGCTCCACGA

TTTTCTGTGTCAATTGAGCGATTATAAAGATGATG

ATGACAAATA

custom-character

The CLN3 protein sequence is:

(SEQ ID NO: 5)

MGGCAGSRRRFSDSEGEETVPEPRLPLLDHQGAHWKNAVGFWLLGLCNNF

SYVVMLSAAHDILSHKRTSGNQSHVDPGPTPIPHNSSSRFDCNSVSTAAV

LLADILPTLVIKLLAPLGLHLLPYSPRVLVSGICAAGSFVLVAFSHSVGT

SLCGVVFASISSGLGEVTFLSLTAFYPRAVISWWSSGTGGAGLLGALSYL

GLTQAGLSPQQTLLSMLGIPALLLASYFLLLTSPEAQDPGGEEEAESAAR

QPLIRTEAPESKPGSSSSLSLRERWTVFKGLLWYIVPLVVVYFAEYFINQ

GLFELLFFWNTSLSHAQQYRWYQMLYQAGVFASRSSLRCCRIRFTWALAL

LQCLNLVFLLADVWFGFLPSIYLVFLIILYEGLLGGAAYVNTFHNIALET

SDEHREFAMAATCISDTLGISLSGLLALPLHDFLCQLSDYKDDDDK

Conservative changes to the CLN3 protein sequence above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 conservative residue changes, or up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% conservative residue changes) that result in a functional equivalent version of the protein (e.g., that retains at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% of the wild-type enzyme activity) are also within the scope of the invention.

Likewise, in any of the nucleotide sequence encoding the protein and variants thereof, such as in SEQ ID NO: 4, nucleotide sequence changes that do not result in sequence change of the encoded protein in SEQ ID NO: 5 due to, for example, codon degeneracy, are within the scope of the invention. Further, codon optimization of any of the polynucleotide sequence for optimal expression in a specific type of host cell is also within the scope of the invention.

Numerous other neuronal diseases/disorders can be similarly treated by the constructs, AAV vectors, and methods of the invention. A representative (non-limiting) list of the treatable diseases and disorders, along with the corresponding GOI's, are provides in the table below.

Target No.
Diseases
Target Gene (GOI)
GOI Size

1
Ceroid-Lipofuscinosis
CLN3
1403

2
Fucosidosis
FUCA1
1487

3
Giant Axonal Neuropathy
GAN
1880

4
Globoid cell leukodystrophy
GALC
2144

5
Mucolipidiosis Type IV
MCOLN1
1829

6
Neuronal Ceroid Lipofusinoses
PPT1
1007

7
Niemann-Pick Disease
SMPD1
1982

8
Sandhoff Disease
HEXB
1757

9
Sanfilippo syndrome
SGSH
1595

10
Tay-Sachs Disease
HEXA
1676

11
Hunter Syndrome
IDS
1739

12
Sialidosis
NEU1
1334

13
Multiple Sulfatase Deficiency
SUMF1
941

14
Childhood Epilepsy
GAT1/SLCA1
1886

15
CMT Peripheral Neuropathy
FIG4
2810

16
Neuronal Ceroid Lipofusinoses
CLN5
1163

17
Aspartylglycosaminuria
AGA
1127

18
Mucopolysaccharidoses
IDUA
2048

19
Parkinsons Disease/Symptoms
GDNF
722

20
GM1-Gangliosidosis
GLB1
2120

21
Charcot-Marie-Tooth Type 1A
PMP22/MFN2
569

22
Retts Syndrome
MECP2
1583

23
Dannon Disease
LAMP2
1322

24
Mucopolysaccharidoses
NAGLU
2318

25
Mucopolysaccharidoses
ARSB
1688

26
Sly Syndrome
GUSB
2042

27
Biotin basal ganglia disease
SLC19A3
1577

28
Pelizaeus-Merzbacher disease
PLP1
920

29
Neuronal Ceroid Lipofusinoses
TPP1/CLN2
1778

30
Canavan Disease
ACY2/ASPA
1028

31
Beta-Mannosidosis
MANBA
2726

32
Wolman Disease
LIPA
1286

33
Cystinosis
CTNS
1289

34
Mucopolysaccharidoses
GNS
1745

35
Mucopolysaccharidoses
HGSNAT
1994

36
Alzheimer's Disease/Symptom
NeuroD1
1157

37
Salla Disease
SLC17A5
1574

38
Jansky-Bielschowsky disease
CLN6
1022

39
Neuronal ceroid lipofuscinoses
CLN8
947

40
GM2 gangliosidosis
GM2A
668

The sequences of the above genes that can be included in the viral vectors as GOI's are provided below.

The FUCA1 protein sequence is:

(SEQ ID NO: 6)

MRAPGMRSRPAGPALLLLLLFLGAAESVRRAQPPRRYTPDWPSLDSRPLP

AWFDEAKFGVFIHWGVFSVPAWGSEWFWWHWQGEGRPQYQRFMRDNYPPG

FSYADFGPQFTARFFHPEEWADLFQAAGAKYVVLTTKHHEGFTNWPSPVS

WNWNSKDVGPHRDLVGELGTALRKRNIRYGLYHSLLEWFHPLYLLDKKNG

FKTQHFVSAKTMPELYDLVNSYKPDLIWSDGEWECPDTYWNSTNFLSWLY

NDSPVKDEVVVNDRWGQNCSCHHGGYYNCEDKFKPQSLPDHKWEMCTSID

KFSWGYRRDMALSDVTEESEIISELVQTVSLGGNYLLNIGPTKDGLIVPI

FQERLLAVGKWLSINGEAIYASKPWRVQWEKNTTSVWYTSKGSAVYAIFL

HWPENGVLNLESPITTSTTKITMLGIQGDLKWSTDPDKGLFISLPQLPPS

AVPAEFAWTIKLTGVKDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for FUCA1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

FUCA1-DNA

(SEQ ID NO: 7)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

CCCATCTGTATTAAAAATACAAAAATTAGCCAGGC

GTGGTGGCGTACCTGTAAACCCAGCTACTCGGGAG

GCTGAGGCAGGAGAATGGCTTGAACCCAGGAGGTG

GAGGTTGCAGTGAGCTGAGATTGCAGCACTGCATT

CCAGCCTGGGCGACAGAGCAAGACTGCATCTCAAA

AGAAAAGAAAAGAAAAAAGAAAAGAAAAGAAAAGA

AAACAGCTGTGATTCAGCAATAGTCATTTTCTCTC

CTTGTCACTGCCAGAGTGAGGAAGTGCTGGGTTCT

GTCAACATAGGCTCTGACTTCTCATGAGGTGCAAG

AAAGAAGCAGCATGAACAAAGGCATAGATTTTGCA

CCTGGAGACACGTATTCTAGTCCCACCTCTGACTC

AAACTAGCTGCATGATCTTGGGCAGCCCCCCAGCC

CTCTCTGGGCTTCAGTTCCCTCCTCGGTACAATGG

GAAGGGTAGGGAAGAGGATGGTGCCTAGGATCTTC

AAAGTCCCAACTCTGATGTGCTGCCATTCTCTCAC

TGGCATGTGGGAACTGAGTGTGCTACGTGGAGTCA

TGAGACTTCTTCTTCCTTTTCTTTTTCTTTTTTTT

TTTTTTTTTTTTTGAGACCGAGTCTCACTCTGTCG

CCCAGGCTGGAGTGCAGTGGTGCGATCTCGGCTCA

CTGTAACCTCCACCTCCCGAGTTCAAGCAATTCTC

CTGCCTCAGCCTCCTGAGTAGCTGGGATTACAGGC

GCACCCCATGCCCGGCTAATTTTTGTATTTTTAGT

AGAGATGGGGTTTCACCATGTTGGCCAGGCTGGTC

TCAAACTCCCGACCTCAGGTGATCTGCCCACCTCG

GCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCA

CCTTGTCTGTTCAGAGACTTCTGACTTCCGTATTT

CCCTCGCTAATGGCCTCACCTCCCGTTTGAGTATG

TGCAGCATGTGCAAATTGCAGAGGAACTGGGGAAC

TTCCCTGCCAGGCAATCCTGGGTCCTCTTGGCTCT

CCACTTCCTCCTTCCTTCCTTCCTTCCTCCTTCCT

TCCTTCCTTCCTTCCTTTCTTTCTTCCTTGGTCTG

GCTCTGTCGCCCAGGGGCTGGAGTGCAGTGGCGGT

ATCTCGGTACAAACTAAGCTATTTGAAATGCCTCG

GAATTCCCAAAGAAAGCTCAGTAAATACCAGACAG

ATGAAACGGTCCTGCCCGCTCTCCCTCTTTCAGTA

CCCAGTTTTCTCTTTCCTCTCCTTTCATAACGTTT

CTTCCCATCATCCCTCTACCTCCTTATTTCTGTCA

GGGCTGTTAGATACCCTTCCGGTCTGTTATCTCCT

CCTCCAGCCTTGTGCTACAGGACAACTCAAAAGCC

CCCTATGGCTCCCAAGTGATCACTAAATAAAACTC

GTGATCTCACTTCAGCCTACCCCTGCAGGATTGCT

GCGGCAAAATGGACTACTCCCAGAGGCGTGATCAC

GGTTCGGTTCACTGCAGCCCAGACTTCCCGGGCTC

AAGCGATCCCGAACCTCCCACCTCAGCCTCTCGAG

TAGCTGGGACTCCAGACGTGCACCACTACGCCAGG

CTCATTTTGTTTATTTTTTATAGAGACAGGCTAGT

CTCCAACTTGTGGGCTCAGAGCGATCCTCCCGCCT

CGACTTCCGAAAGTGTTAGGATTACAGGCGTGAGC

CACTGCGTCCGGCTCAATGGACTCCTTCTTAAATG

TGAGTTCTCCGCACACACTGGGCCTTGCTCACCTC

CACGATTTAACCTCGCAGTTAAGTCCCTTTTCAAG

GTTTTTATTCGTCCTTCAGCGAAGCGCTGTCAACG

CCTCCCTGCGTCTTTCCCTTCTTGAGCACCAGAGG

GCGCTCCTCCGACCCGAGGAGGAAGCGACTCGGGC

CAACCTGTCCAGGTTGTCCCACCCCTTTTTCCTTC

CGGGCCAATCGTTAGTCAGAGTGGGCGGAGCCGCC

CGCGGGCACCTGCGCGTTAAGAGTGGGCCGCGTCG

CTGAGGGG

custom-character

ATGAGAGCACCCGGCATGCGATCAAGGCCCGCAGG

GCCAGCTCTCCTCCTCCTGCTCCTTTTTTTGGGGG

CTGCAGAATCTGTAAGAAGAGCTCAACCCCCAAGG

AGGTACACTCCTGATTGGCCCTCATTGGACTCACG

CCCACTCCCGGCGTGGTTTGATGAAGCTAAGTTCG

GAGTGTTTATCCATTGGGGTGTATTCAGCGTGCCC

GCGTGGGGGTCTGAGTGGTTTTGGTGGCACTGGCA

AGGAGAGGGCCGCCCGCAATACCAGCGATTCATGA

GGGACAATTATCCTCCAGGCTTCTCATACGCTGAC

TTCGGTCCTCAGTTTACAGCTAGATTCTTCCATCC

AGAGGAGTGGGCCGATCTTTTCCAGGCGGCTGGAG

CTAAGTACGTCGTTCTGACGACAAAGCACCATGAA

GGGTTCACCAACTGGCCAAGTCCAGTGTCCTGGAA

CTGGAACAGTAAGGATGTCGGTCCTCATCGGGATC

TGGTAGGCGAACTTGGGACTGCTCTCCGGAAGCGC

AATATACGCTATGGTCTTTATCACAGTCTGCTGGA

ATGGTTCCACCCACTGTACTTGCTGGACAAGAAGA

ACGGATTTAAAACCCAACATTTTGTTAGCGCAAAG

CATATGCCAGAGTTGTACGACCTGGTAAATTCCTA

TAAACCCGACCTCATCTGGAGCGACGGAGAATGGG

AGTGCCCGGATACTTATTGGAACTCAACTAACTTT

CTCTCCTGGCTGTATAATGACTCCCCTGTGAAGGA

CGAAGTTGTTGTAAATGACAGATGGGGTCAAAACT

GCTCATGTCATCACGGGGGATACTATAATTGCGAA

GACAAGTTTAAGCCTCAATCTCTTCCCGATCATAA

ATGGGAGATGTGTACTTCTATTGACAAGTTTAGTT

GGGGATACAGGCGCGACATGGCCTTGTCTGATGTT

ACGGAGGAATCAGAAATCATCTCCGAGCTGGTACA

AACGGTGTCATTGGGAGGCAACTACCTGCTGAACA

TAGGCCCAACGAAAGACGGGCTTATCGTGCCGATT

TTTCAAGAACGCCTTCTCGCAGTTGGCAAATGGCT

CTCTATTAATGGGGAAGCTATTTACGCGTCAAAAC

CTTGGAGGGTCCAATGGGAGAAAAACACCACTAGT

GTATGGTACACAAGCAAAGGAAGCGCCGTCTACGC

TATCTTCCTGCACTGGCCAGAGAATGGCGTACTCA

ATTTGGAATCACCTATAACCACATCCACGACTAAG

ATCACCATGCTCGGGATTCAAGGTGACCTTAAATG

GTCTACAGACCCAGATAAAGGTCTTTTTATTAGTC

TTCCCCAGCTGCCTCCCAGCGCGGTTCCGGCCGAG

TTCGCCTGGACGATCAAGCTGACCGGGGTTAAAGA

CTATAAAGACGATGATGATAAATA

custom-character

The GALC protein sequence is:

(SEQ ID NO: 8)

MAEWLLSASWQRRAKAMTAAAGSAGRAAVPLLLCALLAPGGAYVLDDSDG

LGREFDGIGAVSGGGATSRLLVNYPEPYRSQILDYLFKPNFGASLHILKV

EIGGDGQTTDGTEPSHMHYALDENYFRGYEWWLMKEAKKRNPNITLIGLP

WSFPGWLGKGFDWPYVNLQLTAYYVVTWIVGAKRYHDLDIDYIGIWNERS

YNANYIKILRKMLNYQGLQRVKIIASDNLWESISASMLLDAELFKVVDVI

GAHYPGTHSAKDAKLTGKKLWSSEDFSTLNSDMGAGCWGRILNQNYINGY

MTSTIAWNLVASYYEQLPYGRCGLMTAQEPWSGHYVVESPVWVSAHTTQF

TQPGWYYLKTVGHLEKGGSYVALTDGLGNLTIIIETMSHKHSKCIRPFLP

YFNVSQQFATFVLKGSFSEIPELQVWYTKLGKTSERFLFKQLDSLWLLDS

DGSFTLSLHEDELFTLTTLTTGRKGSYPLPPKSQPFPSTYKDDFNVDYPF

FSEAPNFADQTGVFEYFTNIEDPGEHHFTLRQVLNQRPITWAADASNTIS

IIGDYNWTNLTIKCDVYIETPDTGGVFIAGRVNKGGILIRSARGIFFWIF

ANGSYRVTGDLAGWIIYALGRVEVTAKKWYTLTLTIKGHFTSGMLNDKSL

WTDIPVNFPKNGWAAIGTHSFEFAQFDNFLVEATRDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GALC and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GALC-DNA

(SEQ ID NO: 9)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TCCTCTGTCATCACCTTGGTATTTCCCATC

TAGTCACGGTATTAAGTGGGTCTTATGCGCTTGTTAAGAGCTGGTAAGAGAAGCTTAACATTCACTTG

ATGGAATGGTTACTGTGGCTTGTATCCACAGGAGCTCCAGCTCATGCTTAAAATACTGTGTTAGAACA

AATGGATCAGAGTGAATTCTGTAACAGTAAATCCACAGAACTGAAAATTACTGACTTGCATCATAAAC

TGGTTGCAGTGGCAAGGCAGAGAGTTCAGATTCGTGTTGTACTGGGGAAAGAAGAAACCAAAGAAAAT

AAGTGGTTCATACACAGGGGACTATTTAACTGATCCAAGCCAGAAGACTACTGAGGGTGAAAGGAGCA

TTATCAGTAATTATGTTTAGACAAAAGTTGTGACTGTCCTTAGTAAACCAGGATAGACGTAGAGTCAA

TTCAAAAAGAAAGAAAGAACAAACATATCTAATGTACATTAAGAACCCAGGGATATCGGGTTCTTAAT

GTGCATATTTATTGGATTGCCCAGAGCTTTGACCTTCAAGTATAATTGAGTTCTTGAAACTTAGATTT

AGGTTTGTGGTTAAGGGGCAAAATAATCAGATTCCAAATAGGGTTCTGCAGACAAATCCCACAGGTCC

TAAAGTCTCTGGGTCTTTTCCTTGCCATTGTGGTATCTCAGGGGCTTGTGTAGGCAATGATAACCAGT

TCCATACTTCTGCTAAGAGAAATTTGGGGATCAGAAAATCTTTCTCTGCAGCTCTTCAGAGTCTCTTT

AATTTACTTCAATAACAAGGAAATCAGAAATCTCAGGACAGTGCTGGATGTGGCAGAAATTCAGGGCA

ATTCACAACTTTCCTACCAATTTAGAGTTACCTGTCTGGAATCACTTCAACTGACAGTGGAAGATAGT

TTATAAAATTGTAGGGGAGGCAAAATTTCACCTTCGTCCCTGTAGGGTCCCAGCATGGCCCTAGTATT

AAATTGATTTAAGATATTAATAGACTGACAGGAGACAACCACACAAATGTTTATTTTACATAGCACGG

GGGCCCTCATTAAAAAAAAAAAAGACCTAAAGCAGCAGTTAAGAGCCAATTGCTTATAGAGTGAAATG

GACAAAAAATAGTAGTTGTGAAACATGATAAGGCGAAGGGGCTTGGGGTAAAGAAGCGACTAGAAAGA

TAGGGATTAACAAATTTTGTTTGGACAGATTTCCCTCGACTTCAACTTTCTGTCCTTGAAGATAACAA

TGTTATTTTATAGGGAAGACATCTTTCACATGGGAATTTCATCTCCTCCTTTTAAGACACATAATATC

CATGACAGTGATCTTGCACCTGCTGTTTTTAAGTGCCTTTAATTTAAAATAGTCAATATGCCACAGCA

GCATATTTTGAGGTGGTATATTATTAACTCCTTCAAGGCTAAAAGCTTTGAATATGCCGGGGTAGTTA

CCAGACTGGAGAACCTTCTCAGCTATTTGCCACTTGTGGAATGCATTCAAATGTACTGAGTGCTTATT

AACTTTTCTCTCAGTCCCTCACTCTGCTGCTCTTCTCGCCTCATCTCACATAAGGGAAAACTCAGGCT

CCAAAAGCAAAGTGATTCCACCAAGATGACAATGGAATCGGGACCTGGTGTCCAAGCCTGGTCCTCGC

ACGAGGTAGATACTCCCTGAGATGCTGGGGAAGAGCCATGGTAGGGCCACTCATGGCCCTCTTCCTTT

GGCGGACCTTGGAATCCACCTTCCCTGCGTTAAAGTGCTCCACCAGGTGACGCCGGAAGAGAAGCCAG

CAGTAAGTACATGTGAAATCCAGTAGCTGACCACAGACACGCGAGCGATAAGAAAAAGCTCGCTGCTT

CTTTTCTCAACACTCCGCCAGCTGCGTCAGAGGCCCTTGACCCGCACTCAAAATGGCGGCGGCGGCGT

CAGCATCAGCGGCCTCCTGCCCGTATCTATCGTGGCGGCGACGGGACCCGCCTCCCTGGGCGCCGG
custom-character

ATGGCCGAATGGCTCCTTTCAGGATCATGGCAGCGCCGA

GCTAAAGCGATGACGGCTGCCGCGGGCTCTGCTGGGAGAGCAGCTGTTCCTCTTCTGCTTTGTGCCTT

GTTGGCACCTGGCGGAGCCTACGTTTTGGATGACTCTGATGGATTGGGTCGCGAGTTCGATGGTATCG

GTGCTGTGTCTGGTGGCGGAGCCACGTCCAGGCTGCTGGTAAATTACCCGGAACCATATCGAAGCCAA

ATCCTTGACTATCTTTTCAAACCTAACTTTGGAGCGAGCCTTCATATTCTCAAGGTCGAAATAGGCGG

AGACGGGCAGACAACTGATGGCACCGAGCCGTCTCATATGCATTACGCTTTGGACGAAAATTACTTTA

GAGGATACGAATGGTGGCTGATGAAGGAAGCCAAGAAAAGAAATCCCAATATTACCTTGATCGGCTTG

CCGTGGTCATTTCCCGGGTGGCTGGGCAAGGGATTTGATTGGCCGTATGTAAATCTTCAATTGACGGC

CTATTACGTAGTTACATGGATAGTAGGTGCCAAACGCTACCATGACCTGGATATTGATTACATTGGAA

TTTGGAACGAACGATCCTATAACGCAAATTACATCAAAATTCTCCGAAAGATGCTCAACTATCAAGGC

CTCCAGAGAGTTAAAATCATCGCGTCAGATAACCTTTGGGAGTCTATTTCTGCCTCAATGCTGCTCGA

CGCGGAACTTTTTAAGGTGGTTGACGTTATAGGGGCGCATTATCCAGGTACCCACAGCGCTAAAGACG

CAAAGCTCACGGGCAAAAAGCTGTGGAGCAGTGAGGACTTTAGTACCTTGAATAGTGACATGGGTGCA

GGGTGTTGGGGTAGGATACTGAACCAGAATTACATCAATGGATATATGACGAGCACTATAGCATGGAA

CTTGGTAGCGAGTTATTACGAGCAGTTGCCGTACGGTCGATGTGGTCTTATGACGGCGCAAGAACCGT

GGAGCGGGCACTATGTGGTCGAGAGTCCCGTTTGGGTAAGCGCTCATACAACTCAATTCACGCAGCCT

GGGTGGTATTATCTCAAGACCGTTGGACACCTTGAGAAAGGCGGGAGTTACGTAGCACTTACCGACGG

CTTGGGGAACTTGACTATTATCATTGAAACAATGAGTCACAAACACAGCAAATGTATTAGGCCTTTCC

TGCCATATTTTAATGTCTCTCAGCAGTTCGCTACTTTTGTGCTTAAAGGAAGCTTCAGTGAAATACCC

GAGCTCCAAGTGTGGTATACCAAACTTGGTAAAACTAGTGAACGATTTCTTTTCAAACAACTCGACTC

ACTTTGGCTGCTTGACTCTGACGGAAGCTTCACTCTCTCTCTTCACGAAGACGAGTTGTTTACTCTCA

CTACGCTTACTACTGGACGCAAGGGTTCATATCCTCTTCCTCCAAAATCTCAGCCATTCCCTTCCACA

TATAAGGATGATTTTAACGTCGATTATCCCTTCTTCTCCGAAGCGCCGAATTTTGCGGACCAAACAGG

TGTATTTGAATATTTTACTAACATTGAGGACCCAGGAGAGCATCACTTCACCTTGCGACAGGTCTTGA

ACCAGAGACCAATCACTTGGGCAGCCGACGCCTCTAATACCATATCAATTATCGGTGATTACAACTGG

ACTAATCTCACAATTAAATGTGATGTCTATATTGAAACTCCTGACACTGGAGGTGTTTTCATCGCCGG

GCGCGTCAACAAAGGAGGTATCCTTATCCGATCAGCTCGCGGTATCTTTTTTTGGATTTTTGCGAATG

GAAGCTACCGAGTTACAGGTGATCTTGCTGGGTGGATTATCTACGCCCTCGGCAGAGTAGAGGTTACT

GCCAAAAAATGGTATACTTTGACGCTGACGATCAAGGGCCACTTCACAAGTGGTATGCTTAACGATAA

AAGCCTGTGGACGGACATTCCAGTGAACTTTCCTAAGAACGGTTGGGCCGCCATTGGGACACACTCAT

TCGAATTTGCCCAATTCGATAATTTTCTCGTGGAGGCAACCAGAGATTACAAGGATGATGATGACAAA

TA
custom-character

The MCOLN1 protein sequence is:

(SEQ ID NO: 10)

MTAPAGPRGSETERLLTPNPGYGTQAGPSPAPPT

PPEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLML

QVVKILVVTVQLILFGLSNQLAVTFREENTIAFR

HLFLLGYSDGADDTFAAYTREQLYQAIFHAVDQY

LALPDVSLGRYAYVRGGGDPWTNGSGLALCQRYY

HRGHVDPANDTFDIDPMVVTDCIQVDPPERPPPP

PSDDLTLLESSSSYKNLTLKFHKLVNVTIHFRLK

TINLQSLINNEIPDCYTFSVLITFDNKAHSGRIP

ISLETQAHIQECKHPSVFQHGDNSFRLLFDVVVI

LTCSLSFLLCARSLLRGFLLQNEFVGFMWRQRGR

VISLWERLEFVNGWYILLVTSDVLTISGTIMKIG

IEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFF

HNYNILIATLRVALPSVMRFCCCVAVIYLGYCFC

GWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVT

FAAMQAQQGRSSLVWLFSQLYLYSFISLFIYMVL

SLFIALITGAYDTIKHPGGAGAEESELQAYIAQC

ODSPTSGKFRRGSGSACSLLCCCGRDPSEEHSLL

VNDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MCOLN1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

MCOLN1-DNA

(SEQ ID NO: 11)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
ACCCTGACCCTGGCTCTGGGCCGGGCACTC

TGCCGGATCCCAGCTCCAAACCCCTCCCCGGCTCCAGATCCACCCCCAGCCCTACTCCTGTGGAATCT

TCTGACCCAAAGGCTGGGCACGACGCTGGTCCCGACCTTGTGCCCAGCCCAGACCTTGATCCTGTGCC

CAGCCCAGACCCTGATCCTGTGCCCAGCCCTGATCCCAACCCTGTGTCCTGCCCTGACCCCTGTTCTC

CCACTCGTGGCACTGTCAGCCCAGCCCTCCCTACCGGCGAGAGTCCAGAGTGGGTACAGGAGCAAGGG

GCACTGCTGGGGCCTGATGGCTGAAGGAGACGCCGGCATCCTCGGGGGCCTGGGGAAGTTGTGTGTTG

TGCAGTCAGTAAAATCCTCCCACTGCCTCCGGGCTCTGTGTCGTGGCTTGCCTTTTGTGCTTTCTTTC

TGAGCACAGCCCCTTGCTCCGGAGATGGGACATTGTGGCCAGGGCCAGCCACAATCTGGAGCTCCAGT

GTCCTGGCTTCCTTCTTGGGCCCACCAGCTAGACTTTCCAGCTTAACCCACAGTGTCTCATCCTGGTC

CATCCCACTAGTCACCACTCTCTGTTCCTCTCACTTACCCCTTGCTCTTCAAAGCCCATACAGTAGGT

ATACAAGTGGACAAAAAAAGTTGCTCATTTATGCAATCAACAAACATCTCTGGATTGCTGGGGTCTCA

GCAGGGAACAAGATAAATATGGCCTCGACCTGCATGGAGCTCATAGATACTAAATTCAGAATACTTAA

AAAATAATTACGGGGTATAGTACATTCTAGGAGAAGCATAACAAGACTTCTGATATAAATGGCAGGCA

GCTTTCTCAATGAAGGATTTTGTAATCCCAATAATCACTAATTTAATAATCAGTACTGTTTGCCCAGC

CTTATGCGATAGTTTTTGCATTCTCTCATTTAATCCTCTCAACAGCCCCAGTAGGTAGATGACTTTGA

ATATCCCCATTTTGCAAATGAGAAAATTGAGGCACATTTTTTTTTTTTTTTTTAGACAGTCTTGCTCT

GTTGCCCAGGCTGGAGTGCAGTGGTGTGATCATAGCTCACTGCAGCCTCGACCTCCTGGGCTCAAGCG

ATCCTCCCACCTTAGCCTCCCGAGTAGCTGGGATTGCCGGTGCATGCCACCGCCCACTGCGCTCAGCT

TGGAGTTGAAGGGACTCTGGAAGATGTAGAAGTGGCATTGTCAGTGCCTAGATTTAAATCCCAATTGC

CCTCCAGGGTCCAAATTCTTAACCATTACGCTCCAGGGCAAAAGTATGCAAAGGCTCTGGGGCTATAG

AAAGATGAGCTTTGGATGGAGGTAGGAGCCAGATCAGAGGGCCCTGATAGACGAGAGTGGGGACTCTG

CCTGTCATTACAGAGCAATGGGAAGCCGAGGGCAGGTTCTCGCAGGAAGGATAGGAATTATTCTTTGA

AGATGCTTGTGGCTGCTGGGTAGAGAGTGGAGTGGAGGGAGGCTGAGATCGGGGAGGAGGTTGCTGCA

AAGATCCAGGCCAGGAATGTTGGAAGACTCTGGGCTGGGGGCCATGGGGTGGGGATAAGTGGTTCTAT

TTGATACATAATTAGGAAATCGTGTTTGCTGAAGATGCGCAGGAGAAGGGTAAAAGGAGTTTCTGGGA

GAAAGAGGAAGACAGCGTTGAGATAGTAGGCAGGGTCATCACCAGGCACCAAGGAGGATAAGGGGTCA

AGCTCTGGACATGGAAGTCACAAGCCTGGCACCGGATTCGGGGCATGGCCGGGAGCCAGGGCAGAGCT

CGTCGTTGCCAAACTCAGAGTCAGCCCATCCCCCGCCACCCAGAGCGCGTCGGCGCTAGGACCTAGCG

ACTGCCTTCGACCCAGAGGGCGCCGGCAGAGGCACGCATGCGCGCTGTTCCGGCAGGGGTTGTCGTGG

CGCAGGGGGCGGGACCAGAGGCGGTCACGTGAGGGGCTCTGGGCTACCGGGTCACGTGACCGAGGC
custom-character

ATGACTGCGCCGGCAGGTCCACGAGGGTCTGAAACAGAA

CGGCTCCTTACTCCCAATCCCGGCTATGGGACACAGGCCGGTCCTAGCCCTGCCCCACCCACACCCCC

TGAGGAGGAAGATCTGAGGAGACGGCTCAAGTATTTCTTCATGAGCCCGTGCGATAAATTTCGAGCTA

AGGGACGAAAGCCGTGCAAGCTGATGCTCCAGGTGGTAAAGATTCTCGTAGTTACTGTGCAACTCATC

CTTTTCGGTCTGTCCAATCAGTTGGCAGTCACTTTCAGAGAAGAAAACACTATCGCTTTTCGGCATCT

GTTCCTGCTGGGTTATAGTGACGGTGCAGATGACACCTTCGCCGCCTACACTCGCGAACAACTTTACC

AGGCTATTTTCCACGCGGTAGATCAATATCTTGCGCTCCCCGACGTTTCATTGGGGCGGTACGCCTAT

GTTCGCGGAGGAGGCGATCCCTGGACCAACGGCAGTGGTCTCGCATTGTGCCAACGATACTACCACCG

GGGGCACGTAGATCCCGCCAACGACACCTTCGACATAGACCCGATGGTAGTAACAGACTGTATTCAGG

TGGACCCCCCCGAGAGGCCACCTCCACCACCTTCCGATGACCTGACGCTGCTCGAGAGCAGCAGTTCT

TATAAGAATCTTACCCTTAAATTCCATAAATTGGTAAATGTAACCATCCATTTTCGCCTCAAAACTAT

CAACCTGCAAAGCCTCATAAATAACGAAATTCCGGATTGTTACACTTTCTCTGTTTTGATAACATTCG

ACAATAAGGCCCACAGCGGAAGGATTCCGATATCCCTTGAAACACAAGCACACATACAAGAATGCAAA

CACCCTAGTGTCTTCCAGCATGGCGATAATAGTTTTAGACTGCTGTTCGATGTAGTTGTGATCCTTAC

ATGCTCACTGTCATTCCTCCTTTGTGCACGATCACTTCTTCGGGGTTTCCTGTTGCAAAATGAGTTTG

TGGGATTTATGTGGAGGCAACGAGGACGCGTCATATCTTTGTGGGAACGGCTTGAGTTCGTCAATGGA

TGGTACATACTTTTGGTTACATCCGATGTGTTGACTATATCCGGTACAATTATGAAAATTGGCATTGA

AGCGAAGAACCTCGCCAGTTATGACGTTTGCAGTATCCTTCTGGGAACGTCCACCCTCCTCGTATGGG

TAGGAGTCATACGGTACCTGACTTTCTTCCATAACTATAATATACTGATCGCAACCCTTCGAGTCGCG

CTTCCGAGCGTGATGAGGTTCTGTTGCTGCGTAGCTGTTATCTACCTGGGATACTGTTTCTGTGGATG

GATCGTACTCGGCCCGTATCACGTAAAGTTCCGGTCCCTTTCTATGGTCTCCGAATGTCTTTTCAGTC

TCATCAACGGTGACGATATGTTCGTCACCTTTGCTGCGATGCAAGCTCAACAAGGGAGGAGTAGTCTG

GTTTGGCTTTTTAGTCAACTGTACTTGTACTCCTTTATCAGTCTTTTTATTTACATGGTGCTCTCATT

GTTCATCGCACTTATCACGGGCGCCTACGACACGATTAAACATCCGGGTGGAGCCGGCGCCGAGGAAA

GTGAGCTCCAAGCCTACATAGCGCAATGTCAAGATTCCCCGACCTCAGGCAAGTTCAGGAGAGGCTCC

GGAAGCGCCTGTTCTTTGCTTTGCTGTTGCGGGAGAGACCCATCCGAAGAGCACTCCTTGCTGGTCAA

TGACTATAAAGATGACGACGATAAATA
custom-character

The PPT1 protein sequence is:

(SEQ ID NO: 12)

MASPGCLWLLAVALLPWTCASRALQHLDPPAPLP

LVIWHGMGDSCCNPLSMGAIKKMVEKKIPGIYVL

SLEIGKTLMEDVENSFFLNVNSQVTTVCQALAKD

PKLQQGYNAMGFSQGGQFLRAVAQRCPSPPMINL

ISVGGQHQGVFGLPRCPGESSHICDFIRKTLNAG

AYSKVVQERLVQAEYWHDPIKEDVYRNHSIFLAD

INQERGINESYKKNLMALKKFVMVKFLNDSIVDP

VDSEWFGFYRSGQAKETIPLQETSLYTQDRLGLK

EMDNAGQLVFLATEGDHLOLSEEWFYAHIIPFLG

DYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PPT1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

PPT1-DNA

(SEQ ID NO: 13)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TGGTCTGGCACAATGGCTCACAGCTGTGAT

CCTAGAACTTTGGGAGGCTGAGGGGGGCGGATTGCCTGAGCTCAGGAGTTCGAGACCAGCCTGGGCAA

CATGGCGAAACCCTGTCTCTACAAAAAACACAAAAAATTAGCGGGGCATGTTGGTGGTGTGTCTGTAA

TCCCAGCTACTCGGGAGGCAGAGGCACGAGAATCGCTTGAACCCGGGAGGTGGAGGTTACAGTGAGCC

AAGATCACGCCACTGCACTCCAGTCTGGGGGACAGAACAAGACCCTGTCTCAAAAAAAAAAAAAAATT

GCATTCAGATTGCTTCACAAGTGTCTTTCAGTTATTGCTCCAGTTTAAAGAAACCTTTAAAGAAATTA

TAAATAGTTCATTAAAGGCAGGAAACTTCATTGAGCGGGCTATATTCACAGAAAAATCCTGAAACTAC

TTCAATTTGTAAGTCTTAAGTTAAAATAAAATGCTTATACAATAAGCTTATTTTTCTTAAAACAAAAC

TGTATACTGTACTGTATAATGCTTTATGATTCTGCATTTTTTTTTCTTTGAGACAGAGTTTCACTCTT

GTTGCCCAGGCTGGAGTGCAGTAGCTCAATCTTGGCTCACTGCACCCTCTGCCTCCTGGGTTCAAGTG

ATTCTCCTGTCTCAGCCTCCTGAGTAGCTGGGATTACAGGCACCCACCACCATGCCCGGCTAATTTTT

TGTATTTTTAGTAGAGATGGGGTTTCATCATGTTGGCCAGGCTGGTCTCAAACTCCCAACCTCAGGTG

ATCCACCTGCCTCAGCCTCCCAAAGTGCGCCCAGTGGATTCTGCATTTTAATCGACTTTTCAACTAAC

AACTTACCTCTAGTCCCAATGGCATGGAATAGAAGAGATTACAGACCGTGGGTTTGTAATCGACTTTT

CTTTTACAACATATTAAGGGCATTTTTCATGTCACTTTATGTAAATTTACCTCATTTTTCTTTTTTGA

GAGAGACAGGGTCTCACTGTTGCCCAGGGCAACAGCGAGATCATAGCTCAGTGCAATGGCGAGATCAT

AGCTCAATGCAGCCTTGAACTCCTGGGCTCAAGTGATCCTCCCACCTTAGCCTCCCCAGTAGCTAGGA

TTACAGGCACATACCACCACCCCTGGCTAATTAAAAAAAAATTTTTTTTTTGTAGAGATGGGGTCTTG

CTATGCTGCCTGGGCTGTACTCTCTTTTTATTTATTTTTTATTCTTATTTTTTGAGACAGAGTTTTGC

TCTTGTTGCCCAGGCTGGAGTACAATGGTATGATCTCAGCTTACCGCAACCTCTGCCTCCCGGGTTCA

AGAGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGATTACAAGTATGCGCCACCACACCCGGCTAAT

TTTGTAATTTTAGTAGAGACGGGATTTCTCCATGTTGGTCAGGCTGGTCTCGAACTCGCTACCTTAGA

TGATCTGCCCACCTCAGCCTCCCAAAGTGCTGGGATTACAGGAGTGAGCCACCGCGCCCGGCCCTATA

CTCATTTTTTATAAAACTGGCCTCATATTATTCCATTGTATAGTGGATACACTCTAATTTCTTTATAA

ATTATTTAAACTATTTTTTGATGTTTTGTTGAAAAAAAACTTGAGCAGGGAACTGATATTATGAAGGT

GGATTGAGGGATGAATGTGGCAATAGAGCATAAAATGAATTAAAGAGGAGAGAATGGAAAAGGAAATG

GTTGATGAGAGACCCTTGAAATAATCCAGCTGAGATTAGGCCAGTTAGTGGCCATGGGTTTCCCCCTC

ACTCTTATGCATCCAACATATGCTTTCGTCCGTCTTGAAGTCCCGACATTTCTAGAAAACACAGTTGT

CTTTCTCCTCTCTACCTTAGCTCATCTCAGTCCTTCTGAATTTCATCTTTGCTTGTTGAAATCCTACC

TCTCCTTCAATATCCAGAACAAACCCCACACCCTGCCATGATTGGTCCTGGCTGGAAACCGTCCCTCC

TTCTTTCTTCCTTCCTCTGTGCATGTTTCTTGCAAAGGCAGTACAGGGCAGTGGTGAAGAGCAACGAC

TTTGGAACCACCAATTTGCTATCTCTGTGACCTTGGGCACCTTACTCAGTGCCAATTCGCAGTGCCTC

AGTGTCCTCACCTGTCAGGGGGAGAAGTGCATACAGCATTGTTATGAAGAGTGAATTAGTTAAAGGTT

GTAAGAATAGTGCCTGATAGCATCTGATCAGCACTGAATATATGTTAGCAATTATTTTGATTCACCGC

AGAGGGCGGTCTACGAGAGCGCAGAGCCCCACTCGGCCAGCGGGGTCTGGCGGGGGACCTGTCGCGCT

GAAAGCTCCAGGGTAGGGCCGACGCCCATCAGGCTGGGCATCCGTTCGGGATGCGCAGGTTGCGATCT

GCAACCGGCGGCGCCACGCCCAGGCGGGCGGAGCGCGGTTCCCGGAGTCTCGCGCCCGCGGTCA
custom-character

ATGGCGTCTCCTGGTTGTCTTTGGTTGCTTGCCGTCGCGTT

GTTGCCTTGGACATGTGCTTCTCGGGCTTTGCAGCACCTCGATCCCCCAGCCCCATTGCCTCTTGTAA

TCTGGCATGGCATGGGTGATTCATGCTGTAATCCCCTCAGCATGGGGGCCATAAAGAAAATGGTAGAG

AAAAAGATCCCAGGCATATACGTACTCTCACTTGAGATAGGGAAGACCTTGATGGAAGACGTTGAGAA

CTCTTTTTTTCTCAATGTTAACTCCCAAGTCACTACGGTATGCCAGGCGCTGGCGAAAGATCCTAAAC

TTCAACAGGGGTATAACGCCATGGGATTCTCTCAAGGTGGGCAGTTCCTTAGAGCGGTCGCCCAGAGG

TGTCCATCCCCCCCAATGATTAATTTGATCAGTGTGGGTGGACAACATCAAGGCGTGTTTGGCCTCCC

CAGATGTCCAGGTGAGTCATCTCATATCTGTGATTTCATCCGGAAGACATTGAACGCAGGTGCGTATT

CAAAGGTAGTGCAGGAGAGGCTGGTGCAGGCTGAGTACTGGCACGACCCTATCAAGGAGGATGTCTAC

CGAAATCACTCAATTTTCCTTGCAGACATCAACCAGGAGCGAGGCATTAATGAAAGCTATAAAAAGAA

TTTGATGGCTTTGAAAAAATTTGTTATGGTCAAGTTCCTCAATGACTCAATAGTCGATCCGGTGGATT

CCGAGTGGTTCGGGTTTTATCGGTCAGGTCAAGCGAAAGAAACAATTCCCCTTCAAGAAACGTCACTT

TATACGCAGGACCGACTCGGCCTGAAGGAAATGGATAACGCTGGGCAACTGGTATTTTTGGCTACCGA

GGGCGATCACCTGCAGTTGAGCGAGGAATGGTTCTACGCTCACATCATACCCTTTCTTGGGGACTACA

AGGACGACGATGACAAGTA
custom-character

The SMPD1 protein sequence is:

(SEQ ID NO: 14)

MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMG

LVLALALALALALALSDSRVLWAPAEAHPLSPQG

HPARLHRIVPRLRDVFGWGNLTCPICKGLFTAIN

LGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSI

VHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHW

DIFSSWNISLPTVPKPPPKPPSPPAPGAPVSRIL

FLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPA

SRPGAGYWGEYSKCDLPLRTLESLLSGLGPAGPF

DMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVR

KFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSS

RWLYEAMAKAWEPWLPAEALRTLRIGGFYALSPY

PGLRLISLNMNFCSRENFWLLINSTDPAGQLQWL

VGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYY

RIVARYENTLAAQFFGHTHVDEFEVFYDEETLSR

PLAVAFLAPSATTYIGLNPGYRVYQIDGNYSGSS

HVVLDHETYILNLTQANIPGAIPHWQLLYRARET

YGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHK

GHPPSEPCGTPCRLATLCAQLSARADSPALCRHL

MPDGSLPEAQSLWPRPLFCDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SMPD1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SMPD1-DNA

(SEQ ID NO: 15)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AGCACTTACTAGCTAGCTGTGGGATCTTGA

GCCACTTACTTAATCCTACTTTCCTTCTCCGTAAAATGGGGATAATTATAATACCGACTTCCAAATTT

GTTGTGAGGATTAACGTAAGGCAGAGTCCTCAGAAAAGTACCTACAGAGGGTTATTCGGGCCAAGGGC

CAAGGTTGAGGACTGCGACCCAGGACACACTTGCAAGTTGTCTTGGGGGAGCACTCTGGACAACAAAA

GAGAGGCTCATATTTTCAAAGAAAAAAAGATGAATTAGGAGAGGAAATGAATACAAAAGTTGTTCATC

AGGAATTCTCATTGTTTACAGAAATAACACTGGTTATACATTGTTTAGCGCTTGGCTATACATTGTTG

AACTATAAGGTGTATGGCATTTAATGGCTACTTGGCATAGCAAGTGGTTTCAAGAGATAATTACTTAG

CTCAAAGAAGAGTGAGAGTGACTGTTGCTACATTTTAAATGCCTGTCTGGGCCTGATAATTTAAAGGG

GCTCATCTTCCTTAGATAAAAAGGTTTTGTTTTGTTTTGTTTTTCATAGTACATAATCTTAAAAATGC

ATGCTAATTATTACTGTGAGTACTCTATCTGAGATGATGTCCCCAGAACTGGGGGGAAAAAACACTTG

TAAAAAATTATCAAAGGAAAGAACTGACAGGACTTGATAGCTCTGAGGATTCCTCAGAAGCACTCGTC

AAACAGCTTAGGGTTTAATTGCTATTCTGCCACTTAACTTCTTTGTGCCTCATCCTATCTGTAAAGGA

GGGTAATAATAGTATTTGCAGGGACCAAGGGAAACTTTCCCTTCGCCCTCTGAAATTCTGCTGAAAAA

TCAACCCACAAAAAACAGATTAATTGAAGAAAAGGCATAGAAATTGTATTAATGTGTCCACGGGGAAC

CACAGAGTGACTACCCACTTCCCAGACGAGTTCAGAAGCTTAGGTGTCATTCAGGCAAAGGGGGTTGT

GGGAGTGAGGGGAAGAGGAATTCTGCTGAGGGAGAAGGAATGGATCAGGGAACAGATTAACTAGCACA

TTATCATGTGAAGGGGTCTGTTCAGGTGTGATTATATTCTTGGTTTTGTAGGGAGGGGAAGAAAAAAA

CCGTTGTTCCTTTTGATGGGTCTGGACGCTAGGTAACGGCTTTGGGAGAGAGGGCGCGGGAGTAGGAA

GGCCAGACACACCTTAAGGCTTAACTTAGTAAGTCAAACCACCATATTTTGGGTATGGATTTCTGAGC

CCCAATATAATAGGTACTTCTTAGGGTTGTTGTGAGAATTGAAGATTATTAATTATAAAGTGCCTGGG

TTGGTGCTTGGCACATCATAAACAACTCCATAAATGCTCGCTTTTACTGTCGTGGATACACGGAGGTG

GGAGACCCAATTGGGTTCCCGCCCATGTTATTGGCCCCCACGGCTATATGGTCTTTACGGCTTCCTAG

TCTCTTCACCATCTCTAAGGTTTGTTTCCTCATCTGAATCACAGGTGAGTGATTCTCAGGGTGACTCA

AGAGGGCTGGTGCCAGTGGCAGAGCATGGGGAATCGAGGGAAGGCGCCTTCCTGTCAGAGGCAACACA

CCCAGTGGGAGGATCCTGCCCGCCCTGCTCTCTCCTACCTCCCCTTCCCGGGCTAAACGCTGGGGTCG

GTCTGGCAGCTATTCCGGGAATCTGAGCGCGGATTCTGACAAAGGAGACGTCTTCCACCGACCACATC

ACATGGAGCTCCAAAGCACGAGCACGGCCTCCCGCGGCTGTGACCTCAAGGCGGAGCCCCTGGTGACC

TCAGGGAGAGTCCCCACCCCCGCAGCCCGTGCGCCCGGGGCAGGGCGGGGGCAGGGAGAGGGGGCGGA

ATCGGGGCGGTCCCGGGAGCGCCCCGCCCCCTCCGCCTCCGCAGCGTTGACAGCCGCCCGCCACCGAG

AGATCAGCTGTCAGAGATCAGAGGAAGAGGAAGGGGCGGAGCTGCTTTGCGGCCGGCCGCGGAG
custom-character

ATGCCAAGGTATGGTGCTAGCTTGAGGCAATCCTGTCCTCG

CTCTGGCAGGGAACAGGGACAGGATGGTACGGCGGGAGCCCCGGGCCTGCTGTGGATGGGGCTCGTGC

TTGCATTGGCGCTCGCCCTTGCTCTGGCGTTGGCACTGTCTGACAGTAGAGTCCTTTGGGCGCCTGCA

GAAGCCCACCCACTGTCTCCCCAAGGGCACCCCGCCCGACTCCATCGAATCGTACCTCGCCTGCGGGA

TGTTTTCGGTTGGGGCAATTTGACCTGCCCAATATGTAAAGGCCTCTTTACGGCCATCAACCTCGGTC

TCAAAAAAGAACCTAATGTCGCTCGCGTTGGCTCAGTTGCCATCAAGCTGTGTAATCTGTTGAAAATA

GCTCCGCCGGCAGTGTGTCAAAGTATTGTGCATCTGTTCGAGGACGATATGGTTGAGGTATGGCGACG

ATCCGTCTTGTCCCCCTCTGAGGCCTGCGGGTTGCTGTTGGGGTCTACATGTGGCCATTGGGACATAT

TTAGTAGTTGGAACATCTCATTGCCGACGGTCCCGAAGCCCCCTCCTAAACCTCCTAGCCCGCCAGCG

CCTGGTGCCCCTGTGTCTCGGATTCTCTTTTTGACAGATCTCCACTGGGATCATGATTATTTGGAAGG

GACCGACCCCGACTGTGCTGATCCTCTTTGCTGCCGCCGCGGTAGTGGACTTCCTCCTGCCTCTCGAC

CAGGGGCGGGCTACTGGGGGGAGTATAGCAAGTGCGACCTTCCCCTCCGAACCCTCGAGTCACTGTTG

TCAGGGCTCGGCCCCGCAGGACCTTTTGACATGGTTTACTGGACAGGAGACATACCAGCACACGACGT

TTGGCATCAGACTCGGCAGGATCAGCTGCGGGCGCTCACTACTGTTACAGCGTTGGTTCGCAAGTTTC

TGGGTCCCGTCCCAGTGTACCCCGCTGTTGGAAACCACGAGAGTACGCCGGTGAACAGTTTCCCCCCT

CCGTTTATAGAAGGAAATCACTCCTCTCGGTGGTTGTACGAAGCGATGGCAAAAGCCTGGGAGCCGTG

GCTCCCTGCAGAAGCATTGCGGACATTGAGAATTGGCGGGTTTTACGCCCTGTCCCCTTATCCAGGCT

TGCGGCTCATATCTTTGAATATGAACTTCTGCTCTCGGGAGAATTTCTGGCTTCTGATCAATTCTACC

GACCCTGCAGGACAACTTCAATGGCTTGTAGGCGAACTGCAAGCGGCCGAAGACCGCGGTGACAAGGT

GCATATAATCGGCCACATTCCGCCTGGGCACTGCCTTAAAAGTTGGAGTTGGAACTACTACCGGATCG

TTGCACGGTATGAAAACACTCTTGCAGCGCAGTTCTTCGGGCATACGCATGTTGACGAGTTCGAAGTA

TTTTACGACGAGGAAACTTTGAGTAGACCACTCGCCGTTGCATTCTTGGCGCCGTCAGCTACAACTTA

CATAGGTCTGAACCCAGGGTACAGAGTATATCAAATAGACGGGAATTACAGCGGCAGTAGCCATGTAG

TCCTGGACCACGAAACATATATACTCAACCTTACCCAGGCAAACATTCCGGGCGCGATTCCTCACTGG

CAACTGCTGTACCGCGCACGGGAAACTTATGGTCTCCCCAACACACTTCCGACAGCCTGGCATAACCT

CGTGTACCGCATGAGAGGGGACATGCAGCTTTTCCAGACATTTTGGTTTCTGTACCATAAGGGGCACC

CCCCTTCTGAGCCTTGCGGTACACCCTGCCGCTTGGCCACCCTTTGTGCTCAACTCTCCGCACGGGCG

GATAGCCCTGCATTGTGTAGGCATTTGATGCCAGATGGGAGCTTGCCTGAAGCCCAAAGTCTGTGGCC

ACGGCCCCTGTTCTGTGATTACAAGGATGATGACGATAAGTA
custom-character

The HEXB protein sequence is:

(SEQ ID NO: 16)

MELCGLGLPRPPMLLALLLATLLAAMLALLTQVA

LVVQVAEAARAPSVSAKPGPALWPLPLSVKMTPN

LLHLAPENFYISHSPNSTAGPSCTLLEEAFRRYH

GYIFGFYKWHHEPAEFQAKTQVQQLLVSITLOSE

CDAFPNISSDESYTLLVKEPVAVLKANRVWGALR

GLETFSQLVYQDSYGTFTINESTIIDSPRFSHRG

ILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHI

VDDQSFPYQSITFPELSNKGSYSLSHVYTPNDVR

MVIEYARLRGIRVLPEFDTPGHTLSWGKGQKDLL

TPCYSRQNKLDSFGPINPTLNTTYSFLTTFFKEI

SEVFPDQFIHLGGDEVEFKCWESNPKIQDFMRQK

GFGTDFKKLESFYIQKVLDIIATINKGSIVWQEV

FDDKAKLAPGTIVEVWKDSAYPEELSRVTASGFP

VILSAPWYLDLISYGQDWRKYYKVEPLDFGGTQK

QKQLFIGGEACLWGEYVDATNLTPRLWPRASAVG

ERLWSSKDVRDMDDAYDRLTRHRCRMVERGIAAQ

PLYAGYCNHENMDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HEXB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HEXB DNA

(SEQ ID NO: 17)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GGAATGAAGTCCTCAAGAACCTGCCTGTCC

AAGGATTCCTAAGGAAGCTGTTTATCCCGCTGTTTATCCCCAGAGGGTAAACTGTGTGGCTGGTTGCA

GTATCTGTTCCAGACACATAACAGCCAGTCCCAAAAGCGCAGCTGAAACTCTGTTTCCTTTAACCATT

CAGACATTTTTAAATGCATATTCTAAGAATTATTAATAAATGCAAATGAATGATTTGCCACAGATTCA

TGGGCTAAAATACTAACCTGCACCTCCCCAACCAGATGTGAGCCCCACTATAAGACTGCACAGAAAAC

CACAAAGGCAGGGGCATGACACATATACCTCATACCATTAGGTGATGCAACTAGTTTTCTTTCCTTTT

TGGAATATAATTTTTTATGATGAGTAAACATGGCTGAGTGGAAGAAAGGAAGCAACAAAGTCCTAGAG

CTCCAGTGTTAGGAAGACTTTACAAAGCACCCAGTAATTTCCACAGTGACTTGAGATATAAAAAATGG

TGAGGAGCCAGCTTCACTCCCACCTCAAGCTAAGCATCTACTGTCTACTCCATTCTAACCAATGCCCA

GTGTTTTGGAGAATGACCATATGAACCTATGGGAATGCATCAGGTTTCCAAAGGGTTAAAACATTCAT

TAGCATTCTCAATGCTCCACCACTGTAGTTGCTATTTTAATTAGTACATTCAATCTGGAGTATCTGGA

GGAAGACTTTAAACCTAAACCTCAATAGACTGTCTACTTACTCTTGTGAATCTGCCGCCTCTCTCAGA

GCAAATGCTGCCCTGAGTGAAGGAAGAATGAGGCTCCCTGAAACTAGGTGCACAGGCACCAAAATGCT

TACACATTGAGCTGGAATCATGCTAGGCCCAGAACACATTTCCTTGAACATTAAATTCAGGATGGTGC

AAAACAACATTCACAACCAGACTTACACCTAAGAAAACAATTTGCTTAGAAGACCTTAGGATATAGGA

TCTACATCTCTCCGCATCCTGTGTTTATGCTCCTGTATGTTCCAGGTTGGCCCAACAAGCCAGAAGGA

AGAGCCTAGCCTGTCATCTTGGATACCACCCAGATGGAAAAGCACGTCACAGTCAAAATCACAATCAA

CATTCTTGCAACAATGTTTGATTAAAATAAAAAGTAAACTTGGAAACCCAAGAGGAAATACTTGCTTT

CTGGTTTAAAACTGTGCAAACCTCAAAATATCAGCAGAAACCATGTATACAAGTCACTGAACACACCT

TCAACATAAAATGAATCATCTTTCGAGCATTTTTAAGCCCCCAGAGAAATCACATTTGCATACCAAGT

AAGTGGCCAAGAAAATGCACACATGTACTTAACCTACGTCTGCAAAGAAGACAGAGAAAGGGCTGCTA

TTACTGTGAACATCAAAAGGGCTTCAGTTACAGTAACTTCAGTTCACTTCATGCTCCTAACTCAGGCT

CTCTGCCTCCAATGCTTAGCGTCCCGCACCCTTCTCCAGGTTTTGAACCTGATCTCAATCCAATCAAA

AGAGAAACTAAGCAGATTTTTTTCTGGGCATTTACATTACCGGTAACAATAGAACATTATAAAGATCT

TGTTAACAAAAGTAGCTTCTTGCCAGAGTCTTTTTATTAACACTTGCAACGCTATTTAACAAGCTGGC

CATGCCTGTGTGACACCAAACCGCATGTGGATAAATTCAGTGTTTCATCTCCAGGCCCACCAATTCCT

ATCCTTTGTAACTAATAATGTTAACACGACAGATCAAGAAACTAGTTTTTCAGAAAGCAGTTTTCATT

CATTCTCTATAGACATTTCCGCCGCAGTGAACATGCCCGCACTCAGGGTGTCTGTGCATGGCCCCAAC

TTTCCTCCAAGCCGGGGAGGATGCAACGTGGGCCAACCATCCCGCGCGCTCGGCCCTGGAGGCTGCGG

GGAGCGACGCAGCGCGACATTCACCCCCAGGAAAGCGCTGCTTTCCGCAGAGGAGAGAGGCTGAC
custom-character

ATGGAGCTCTGCGGACTGGGTCTGCCTCGCCCGCCTATG

CTTCTCGCGCTTCTGTTGGCCACTCTTCTCGCTGCGATGTTGGCTTTGTTGACACAGGTTGCTCTCGT

AGTCCAAGTGGCAGAGGCCGCCAGGGCACCGTCCGTGAGCGCTAAACCCGGGCCCGCTTTGTGGCCGC

TGCCTTTGTCTGTTAAAATGACTCCAAATTTGCTCCACCTTGCCCCGGAGAACTTTTACATAAGCCAT

TCTCCCAACAGTACCGCAGGGCCGTCATGCACTCTTTTGGAGGAAGCATTCCGCAGATACCATGGATA

TATCTTTGGTTTTTACAAGTGGCACCACGAGCCGGCCGAGTTCCAAGCTAAAACCCAAGTGCAGCAAC

TGCTCGTATCTATTACACTCCAAAGTGAGTGTGACGCCTTCCCCAATATTAGTAGTGACGAGTCATAT

ACCCTCCTCGTTAAGGAGCCCGTTGCTGTTCTGAAAGCTAATCGGGTCTGGGGTGCTCTGCGAGGCTT

GGAGACTTTCAGCCAACTGGTGTATCAGGACTCATATGGCACCTTTACGATTAATGAGTCTACGATCA

TTGATAGTCCCCGGTTCTCCCACCGCGGTATATTGATTGATACATCCCGGCATTACTTGCCAGTCAAA

ATCATTCTGAAAACGCTGGACGCTATGGCGTTTAACAAATTCAACGTTCTTCATTGGCATATAGTAGA

CGATCAATCATTCCCTTATCAGAGCATTACCTTTCCAGAACTGTCTAACAAGGGATCTTACTCACTCT

CACATGTGTACACGCCTAATGACGTTAGAATGGTGATTGAATACGCGCGATTGAGGGGTATTAGAGTT

CTCCCGGAGTTCGACACACCTGGCCATACTCTCAGCTGGGGCAAGGGTCAAAAGGACTTGCTTACACC

TTGTTATTCCAGACAGAATAAACTTGATTCATTCGGTCCCATTAACCCTACGCTGAATACTACATATA

GTTTCCTTACTACGTTCTTTAAGGAGATAAGTGAGGTTTTTCCCGACCAATTCATTCATTTGGGAGGT

GACGAGGTGGAATTTAAGTGCTGGGAAAGCAATCCAAAGATTCAAGACTTTATGCGGCAGAAGGGTTT

TGGCACCGACTTTAAGAAACTTGAATCCTTTTACATTCAGAAAGTTCTGGACATAATCGCCACAATTA

ACAAGGGTAGTATCGTGTGGCAGGAGGTATTCGATGACAAAGCTAAACTGGCCCCGGGAACTATCGTA

GAAGTCTGGAAGGATTCCGCTTACCCGGAGGAACTGAGCCGCGTCACAGCGAGTGGCTTTCCTGTGAT

ATTGTCAGCACCTTGGTATCTGGACCTTATCTCCTATGGGCAAGACTGGCGCAAATATTATAAGGTTG

AACCTCTGGATTTTGGCGGGACTCAAAAACAAAAACAACTCTTCATCGGTGGCGAAGCCTGTCTGTGG

GGTGAATACGTAGACGCTACGAATCTCACTCCCAGACTCTGGCCACGAGCCTCTGCTGTCGGGGAACG

ACTGTGGTCTTCAAAAGATGTAAGGGATATGGACGACGCCTATGACCGGCTGACTAGACACAGATGTA

GAATGGTAGAGAGGGGAATTGCTGCACAGCCGCTTTACGCCGGGTATTGCAATCATGAGAACATGGAT

TACAAAGACGATGACGACAAATA
custom-character

The SGSH protein sequence is:

(SEQ ID NO: 18)

MSCPVPACCALLLVLGLCRARPRNALLLLADDGG

FESGAYNNSAIATPHLDALARRSLLFRNAFTSVS

SCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFD

KVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDF

AYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRP

FFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGM

GRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAA

QYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTS

DNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWG

QVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKT

IHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSY

PMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTF

QDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRS

RDPHETQNLATDPRFAQLLEMLRDQLAKWQWETH

DPWVCAPDGVLEEKLSPQCOPLHNELDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SGSH and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SGSH-DNA

(SEQ ID NO: 19)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
CACAGTCTCGGCTCACTGCAAGCTCCGCCT

CCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCAGGTAGCTGGGACTACAGGCACCCGCCACCACA

CCTGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCCTGTTAGCCAGGATGGTCTCCATCT

CCTGACCTTGCGATCCGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCTTGAGCCACCGCACC

CAGCCTAATTTTTGTATTTTTAGTGGAGACGGGGTTTCACCATTTTGGTCGGGCTGGTCTTGAACTCC

TGAGGCCTCCATGAGTCATCTCGCTGGCCCCTCCATAACCAGCTCAGTGTCTGTGTGTGCCAAACAGG

CATAGGAGCCTGGGTCGGCCCAGAGACAATCTGCGTCACACACTGTAAACCAAAGGTTCCTTGGGGCC

CAGGGGCTGGAAACCTGGAATCGCTGATGGTGTCTGGGATTGATACTGTGTATTCTGCACTGTTTCTG

AGATATGGCTGGCAGCAGGGTCAGACGCCTCACCTGGGGCGGGAGTCCAGCCACTTCAGCATAGGCCA

GCGCCTGGGGAATGGCAGTGAGGCCAACTGAGAGGCCGGCGACGAAATCCATCTTCAGCCACTGCAGG

GAGTAGCTGGGCAGCCACGCCAGGATGGGCAGCCTCCTCTGCAGGGCCGCAGGGGAGCAGCAGCAGGC

GCTCGGGGCCATCCCGGGGCCAGAGGACCTGGCCTGACCCAGCGCCGTCACCGAAGAAGGCATCTCTA

CGGTGGGGCTGGGGGGTGCAGGTGACACAGACCAGCAGTCAGAGCGTGGCCTTTGAAGAACCCGGCAA

CACTGGTCAGGGTCGGCGGGTGTCAGGAGAGGTCACTATGGGTCTCCCCTCCCCAGGGGGGCGAACGG

CTCTAAGAGGAAGCCAACAATGTGTGCAAGATGGGGACTGGGCCAAGACTGGAAGGCCCACCCCGTCC

CTCATCACCCTCTCTCCCTGAATCCCCCCCGTGCAAATCCTGGGTGCCTTCTGTCCCTCCATCCTCAA

CTCTCCCAGATAAGAAACTGATAAGCGATTCCTCATTGAGAAGTCTGAAGACTAATTAGGCTCAACAC

TTCTGGCCCCTGGAGAACCGACTTCCTTTGCCTTTTTTTCCGTCTCCCCAGGGAATTTAACGGGGAGC

AGCGCAGAGAGAAGCTGGGCCCGCGGGCGCACCGTAGGCTGGCGGGGGGTGCGGGTGGCAGCCAGGAG

ATCCAGCGGGGCTCCGAGGTTTTCCAACTGCGCACCAAGGCGGGCTCCACCCGCTACGGTGGACTGCG

GCGCTCGAGGGAGAGTGGGGGGGTCCTCCGCTCCTGAGGCCACGCCTCGCTCAGCCCCCACCTGTGGC

TTTCACAGCCCTGGAGTTCTAGTTGCTTCTGGGAGGACATCAGAGGCGCCCGGTTAATTCAGGTGCGC

AGCATCTTCCAGGGCCCCGGCGCCCGCGCGCAGAGCCGCCACCCTCACCCCCAGCCCCCCACGCCCCC

GGCCGCTCCGCTCCGGGCAAAATCCACTCCCCGGCCCCCGGCCCCGCCCACAAGGCCGCTGGCTCCGG

ATCCTGGGGTCTCCGGAGGAGACCCTGCGCCACCTGACCGTCCGCGGTCCCTTGGCCCCGAGCAAGGC

CGAGGGCCGCGGGGACCCGGGTAGGGACGCGGCGGGGGAGTGGTCCCCACGGGAGGCCCCCGCACTTC

AGGACTCCGCGCTGGCCCCCGCGTCGGCTGCCCCCGGCGACCCCGGCCACTGTCCGCTCCCCCTGCCC

CTGGTCCCCGCTCGCCGCCCTCGCGGGCCACGGACTCACCCACTCGGCGATGCAGCTTGGGGTCTCCT

GGCGTCGCCGCAGCTGGGTCCGCAGGAATCGCCGGGGACAGGCCGGGGCGGGGTCTGGCGCGCACGTG

ACCGGGGTCGGGGCAGGGGGCGGGGCCGAGCGGGAGACCAGAGAGCCGGAGCCGGATCCCGATCC
custom-character

ATGTCTTGCCCGGTACCGGCCTGCTGTGCTCTCCTTCTG

GTCCTCGGTCTGTGTCGCGCTCGCCCCCGAAATGCGTTGCTCTTGCTGGCCGACGACGGGGGCTTTGA

AAGCGGTGCGTATAACAATAGTGCTATCGCAACCCCTCACCTTGATGCACTCGCACGCCGGTCTCTCC

TGTTCAGGAACGCCTTTACATCCGTCAGTTCTTGTTCACCTAGTAGGGCTAGTCTCTTGACAGGCCTC

CCCCAGCACCAAAACGGGATGTACGGACTGCATCAAGACGTGCATCATTTCAACAGTTTCGACAAAGT

TAGATCCTTGCCCCTCTTGCTTAGCCAGGCGGGTGTGAGGACCGGCATAATTGGAAAAAAACATGTGG

GGCCTGAGACTGTCTACCCTTTCGACTTCGCTTACACGGAGGAAAATGGTTCAGTCCTGCAAGTAGGG

AGAAACATTACCAGAATTAAATTGCTTGTGAGAAAATTCCTGCAAACCCAAGATGATCGCCCATTTTT

TCTGTATGTCGCCTTTCATGACCCTCACCGCTGTGGTCACAGTCAGCCTCAATACGGTACATTCTGTG

AAAAGTTTGGCAACGGGGAAAGTGGCATGGGCCGGATTCCTGATTGGACACCACAAGCGTATGATCCA

CTGGACGTCCTTGTCCCGTATTTTGTTCCAAACACCCCGGCTGCTCGGGCAGATTTGGCAGCACAATA

TACTACTGTCGGGCGAATGGATCAGGGAGTTGGTCTCGTTCTGCAAGAGCTGCGGGACGCAGGTGTCC

TGAACGATACGCTGGTAATCTTTACCTCAGACAATGGTATCCCGTTCCCATCAGGGAGGACGAACCTT

TACTGGCCTGGTACTGCAGAGCCTCTGTTGGTGTCCTCCCCAGAACATCCCAAGAGGTGGGGCCAGGT

GTCCGAAGCTTATGTTTCTCTTCTTGACCTTACCCCGACCATACTTGATTGGTTTTCCATCCCCTATC

CGTCTTATGCAATATTTGGTTCTAAAACGATACATCTTACCGGCCGATCTCTTCTGCCGGCGTTGGAG

GCGGAACCCCTGTGGGCCACTGTATTTGGTTCACAAAGTCACCATGAAGTCACGATGAGTTACCCGAT

GCGAAGTGTCCAGCACAGGCACTTCCGACTCGTGCATAATTTGAATTTCAAGATGCCGTTTCCAATCG

ACCAGGATTTTTACGTAAGCCCGACTTTCCAAGACCTGCTGAACCGCACAACAGCGGGTCAACCAACG

GGGTGGTACAAAGATTTGCGCCACTACTATTATCGAGCTCGATGGGAGCTGTACGATCGGAGTCGAGA

TCCTCATGAAACTCAAAATCTGGCGACAGATCCTAGATTTGCGCAGCTCCTGGAGATGCTTCGGGATC

AGCTTGCGAAATGGCAATGGGAAACCCATGATCCTTGGGTGTGTGCGCCAGATGGTGTACTCGAGGAG

AAACTGTCCCCGCAATGTCAGCCCCTGCACAATGAGCTTGATTACAAGGACGACGACGACAAGTA
custom-character

The HEXA protein sequence is:

(SEQ ID NO: 20)

MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSD

QRYVLYPNNFQFQYDVSSAAQPGCSVLDEAFQRY

RDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTP

GCNQLPTLESVENYTLTINDDQCLLLSETVWGAL

RGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHR

GLLLDTSRHYLPLSSILDTLDVMAYNKLNVFHWH

LVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQD

VKEVIEYARLRGIRVLAEFDTPGHTLSWGPGIPG

LLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL

EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMR

KKGFGEDFKQLESFYIQTLLDIVSSYGKGYVVWQ

EVFDNKVKIQPDTIIQVWREDIPVNYMKELELVT

KAGFRALLSAPWYLNRISYGPDWKDFYIVEPLAF

EGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPR

AGAVAERLWSNKLTSDLTFAYERLSHFRCELLRR

GVQAQPLNVGFCEQEFEQTDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HEXA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HEXA-DNA

(SEQ ID NO: 21)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
CCATCTCAAAAAAGAAAAAAATAAAGAGAG

ATGGGATTTCCTCGTATTACCCATGCTGATCTTGAACTCCTGGGCTCAAGTGATCCTCCCATCTTGGC

CTTCCACAGTGCTGGAATTGCAGGTGTGAGCCACCATCCCCAGCCTGTGATCCATTTTTAATTAAGTT

TGTGTATGCTGTGAGGTAGGGGATCATAGTTCATTTTTCCCACATAGGGATATCTATTTTCTTCATCA

CCTTTTATTGAAAATAACTTGCCTTCCCCACTAAATTAAATTGGTGTCTTCATTGAAATGGAGTAATA

ATCAAATGGCTCTTTTCCTGGACCCTCTATTCCGTTCCATCTATTTGTCTGCCATTATGCCAAAACCC

CACTCTAGTGTATAGTAAGGGGGGATATTTTGGAAGATCAACAAATTTATCTTGTGTAACTTACTTTT

ATGTATGCATAAGAATATTTGGTTTAAAAATCTGGTTAAGTCTAAAAGAGCTCTTTCAGTAATAATTA

AATAACTGAATCCCTGTAATCCACCATGCTCAGCCCCATTAGTAATTTTTATAGCGTCTTTATTTGGA

TCTAGCTCTTTCATCTTGTGTAACTCTTTTAAGTAAATGACTCCTCCCTTCTGGTACAGGTTGAATAT

CCATAAAAGGGTGCCTTGGCATGTGCTCAGTCCTGAAATTCTACTTTGATCTACTGCTCTCATCTTTG

AAACTGCTCTAAACACTCCCCCAAATTATTGATCCTGTGGGCCTGATTATGAACTTGGCTCTTCTGAC

AATACTTCTCAAATCCTGTACCTTTGGTAACATCTCTCCTGACTGGCAGAGTACCCAGACACTTAATT

AATGCTGATGAAAATTAAGATTTAAGCAAAGAAGAAATTGGTGTAAGAATGCAAGCCTTAGGATCTGA

AACTTGATGACTGTGGGATCTAATTTCTGCTTCTTTTGCTACAAGCTCTGTTTTTGAATAATCAACTT

TCAAAGACAAATTGCTTGATGAATCTCTGTATTGTCAGAATGTTTCTTTGATTTCCCATCAAAGCCAT

GTATGTGTAACTAGTAATTAGGTACCTACGACCTGAATATAAATTATCATTATTTCAGTAGCCCTTTA

TTTGTTTTTGAGAAAGGGTTTCACTATACTGCCCAGGCTAAACTTGAACTCCTTGGTTCAAGTGATCC

TGCCGCCTCAGCCTCCTGAATAGCTGGGAGTAGCTGGGACTACAGGGATGTGTTATCATGCCCAGTGA

AAGCCCTTTATTTTTAAAAGTTCATTTTCCTGATCTTTACATGTATTTTAATACTAAAATTAAATTTA

AAAATTTTAAAAAGTACCTACTAACCAAATAATGCCACCCAATAACAATAGCATTATTTGTATTATGT

TCTGGTAATATAGTGGTGAACAAGGAAGACAGGGTCTCTGATAACTGTGGAATTCTCCTTGATCACTT

CTCAAGCCTCTCTTCCGGATACTATTTCTTGGATCTACAGCTGTCTTCCTTCCCCACTTCTGTAGTTC

AGTCTCTCATTATTCTCTACCTCCAATAAAAAGGGGCCTCCTAACTGGTTTCTTATGCAACTACTCAA

CATGGTATTTCTAAAATGCAGATCTTTCGGGATGATTTTCAATTGCTCAGAGAATAAATTCCTTGACT

TTCTACGTAAGGCCCTGCAGGACCAGGCCCCTGTCATTATCTCTGAGCACTCTCCATCTTGCACCCAA

AGCCCCAGCAATATCTTACTGCTTTCAGTAAATACACACCGGGCTATGTGGGGTTTTGTCTGGGGAAA

GGGGATGTGAGTTGTAACTAAGAGATTTATAGTCAATCTTGAAGGGAAGAGCTCATATTGGAGGCAAT

GGAATGCCTCAAGCTGGCTCTGAAAGTACACATTTTTTCCAGTCATAAGTAGATCACATTTGTGTGAT

CTTGTGATCCTCTCTCTAGCAGAGCCGTGCAGACTACCTACTTCCGGCCCTTTCTTGCCCCACGAAAT

TTCACATCACAACGACTTGTGGTTTTAATCCTCCGTTTTTCTGCTTCTGAAGTTACTTCAGCCTGGCA

AGTCCTTTACCTCCCCGTAGGCCTGGCGAGCTGCATCACAACATTCAAGATTCACCCTAGAGCCATCT

GGGAAACTTTCTTCTCCAGGTCGCCCTGCGTCCTCGCCTCCCCACCCCGTTCTTCTCGAGTCGGGTGA

GCTGTCTAGTTCCATCACGGCCGGCACGGCCGCAGGGGTGGCCGGTTATTTACTGCTCTACTGGGCCC

GTGAACAGTCTGGCGAGCCGAGCAGTTGCCGACGCCCGGCACAATCCGCTGCACGTAGCAGGAGCCTC

AGGTCCAGGCCGGAAGTGAAAGGGCAGGGTGTGGGTCCTCCTGGGGTCGCAGGCGCAGAGCCGCCTCT

GGTCACGTGATTCGCCGATAAGTCACGGGGGCGCCGCTCACCTGACCAGGG
custom-character

ATGACGTCTAGCAGATTGTGGTTCAGTCTGTTGCTCGCCGCGGCGTTTGCCGG

CCGAGCCACCGCATTGTGGCCCTGGCCCCAGAATTTTCAAACTTCCGATCAAAGATACGTCCTCTATC

CTAACAATTTCCAATTTCAATATGATGTGAGTTCAGCTGCACAGCCGGGATGTAGCGTCTTGGACGAG

GCGTTCCAAAGATACAGAGATCTCTTGTTTGGCTCAGGCTCATGGCCACGGCCGTACCTTACTGGCAA

GCGGCATACACTTGAAAAGAACGTGCTCGTCGTAAGTGTAGTAACTCCGGGTTGTAATCAGTTGCCCA

CGCTCGAGAGCGTCGAAAACTACACACTCACGATTAACGACGATCAGTGTCTGCTCCTTTCAGAGACC

GTATGGGGGGCGCTGAGGGGCCTTGAAACATTCTCACAGCTTGTTTGGAAATCAGCGGAGGGAACGTT

TTTTATCAACAAAACGGAAATAGAAGATTTCCCCAGATTTCCACATAGGGGCCTGTTGCTGGACACCA

GTCGCCACTACCTTCCACTCTCATCCATACTTGATACCTTGGACGTAATGGCCTATAACAAACTGAAT

GTTTTTCACTGGCACCTTGTAGATGATCCATCCTTCCCTTACGAAAGTTTCACTTTTCCCGAGCTCAT

GCGGAAGGGCTCCTATAACCCTGTTACACATATATATACAGCTCAAGATGTAAAAGAGGTGATCGAAT

ACGCACGCTTGAGGGGGATACGAGTGCTCGCTGAGTTTGACACACCAGGTCACACACTTAGTTGGGGG

CCTGGCATTCCTGGGCTTTTGACACCCTGCTATAGCGGATCAGAGCCCTCAGGGACTTTTGGACCTGT

GAATCCATCTCTGAATAATACGTACGAATTTATGAGCACATTTTTCCTGGAGGTCAGCTCCGTGTTTC

CCGATTTCTATCTGCATCTGGGAGGCGACGAGGTGGATTTTACCTGTTGGAAATCCAACCCCGAAATC

CAGGATTTCATGCGGAAGAAGGGCTTCGGTGAAGATTTTAAGCAACTCGAGAGTTTCTACATACAGAC

CCTTCTTGATATCGTCTCTAGCTACGGTAAGGGGTATGTTGTATGGCAAGAAGTATTTGACAACAAGG

TAAAAATACAGCCCGACACCATAATCCAGGTCTGGAGGGAAGATATCCCGGTTAATTATATGAAGGAG

CTCGAGTTGGTTACAAAAGCAGGTTTCCGAGCGCTTCTCTCTGCTCCTTGGTATCTGAACAGGATCAG

TTATGGTCCGGATTGGAAGGACTTTTATATAGTTGAGCCATTGGCATTTGAGGGGACACCTGAACAAA

AAGCTCTTGTCATCGGAGGGGAAGCCTGTATGTGGGGCGAATACGTAGATAATACGAACCTCGTGCCG

CGATTGTGGCCCAGGGCCGGGGCGGTAGCGGAAAGGTTGTGGTCAAACAAACTTACGTCAGATCTCAC

CTTTGCCTACGAGCGATTGTCCCATTTCCGCTGCGAATTGCTCAGGCGGGGAGTCCAAGCCCAACCCC

TCAATGTAGGTTTCTGCGAGCAGGAGTTCGAACAAACCGATTATAAAGATGACGATGACAAATA
custom-character

The IDS protein sequence is:

(SEQ ID NO: 22)

MPPPRTGRGLLWLGLVLSSVCVALGSETQANSTT

DALNVLLIIVDDLRPSLGCYGDKLVRSPNIDQLA

SHSLLFQNAFAQQAVCAPSRVSFLTGRRPDTTRL

YDFNSYWRVHAGNFSTIPQYFKENGYVTMSVGKV

FHPGISSNHTDDSPYSWSFPPYHPSSEKYENTKT

CRGPDGELHANLLCPVDVLDVPEGTLPDKQSTEQ

AIQLLEKMKTSASPFFLAVGYHKPHIPFRYPKEF

QKLYPLENITLAPDPEVPDGLPPVAYNPWMDIRQ

REDVQALNISVPYGPIPVDFQRKIRQSYFASVSY

LDTQVGRLLSALDDLQLANSTIIAFTSDHGWALG

EHGEWAKYSNFDVATHVPLIFYVPGRTASLPEAG

EKLFPYLDPFDSASQLMEPGROSMDLVELVSLFP

TLAGLAGLQVPPRCPVPSFHVELCREGKNLLKHF

RFRDLEEDPYLPGNPRELIAYSQYPRPSDIPQWN

SDKPSLKDIKIMGYSIRTIDYRYTVWVGFNPDEF

LANFSDIHAGELYFVDSDPLQDHNMYNDSQGGDL

FQLLMPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for IDS and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

IDS-DNA

(SEQ ID NO: 23)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AAATAAGATCACATTCTGAGGTACTGGGTG

TTAGGACTCCAACATACAATTTTTGGGGGGAGGACACTAACACCTAAGTCAAAAAGGACCAAAAGACA

TACCATACAAAGCAAAGGCCCTCTGCCCTGCACCTTCCCTCTTCTGTTCTCATTTTAAATGTTTCTAC

TTTCATTTCTTCTAGTAGATTGTCCCTGTCTTTCTAAATACTATGCTATTTCTATATCAACTTTCTAA

TGTTTTCAACTTTAGACATTGCTGACTTCTTCCTATGATAGATGAGATCACTTATCCATTCCTCTTTT

TATGTACATATTTTTAACCTTGGATTTTGGAAATTGATCAAACCTATACAAGATTACAGAAAATAGTA

TAATAAACCCCAGGTGTTCATCAATGAACTTCATTGGTTATCAACTCATGACAAATTTTGTTTCATCT

CTCCCTGCCATTTTCCCTTCTCCTTTTACTATATAGATTTATTGCCATTTTTAAGTTTTCTATTGTTT

ACTTTTGTATCTTTAAGTAATATCCCTAAATCTGTATTTCTCTTTCTATGAACTGGGGACAGCGACTA

TTGATTTATTATTATTATTATTATTATTTTTTTGCGATAGGCTGGGGCAAAGGAGACAATCCTAAATT

GCTAACCCTAAATTAATGTGCCTACATTTCCTGCCATCTCCCTTCCTCCTCCCAGCTTTTTGTCAACT

GTTGCTGCAGGCCAGGTTCCCAAGGAAGCTGACTAAGATGTAGAGTAATGTGCAGGAAGTTTCTTAGG

GAGTACTCTTAGGATCAACACCTGTAGAAGGGGAGGGGAGGGAAGAAATCAAAATTCAACAGACAGAG

AAAGTGGGCAGTCTCAAAAAAGGCTTCAGTTAACCCCACAGGGAGCTCTGAAGCTGAAATGGCCTTTC

AGAGATGTCCCAAGTTGGGGTAAGGGGCTGCACCTTTGTACCTTCAAGTTGAATCACTGATGTGGGCT

TCCTGAGAACAGGGGTGACCTTGGCTGAGGTACCTATCTTTTTCTAAGACAATTTCTGATGAGGGCTA

ACGACAGCTAACAGCTCTCAAGCCAGCTAGGGAAATAAAATTTTTGGTGTTGAAGGGAGATCTGAGCA

GTGCACCACAGCACCATCACAGCTGTATTTGTACCTTCCCATTGTCCATTGTTGTTTAGTCATAATTA

AGTCATCTGGGCTTTGTTATAGATTGATTCTCAAAGTTGAAAATCAAACTGTGTTTGCAGTATTAGGA

CGGTATAATAGTATTCAGTACAGTACAGTGTAGGGCTAGGATTCCATCTCCCCACAATTGCTGCTCTC

TCTGTTTGGCGCACCCTTCTTGCAGACCTCAATGCGGCTTGCTCCCTCACTTGCTTCAAAATTTTGTT

CAAATGCCACTTCACTAGTGAGGCCCTGCCTGGCCACCCCATAGAAAATAACAAGCATGCCCCGCACC

CACGCTTTATTTTTCTCCAGACCGGGTATGCCCACCGACACTCTCTATATTTTTTTATTGTTTTAAGC

TCCACCAAAGCAGGGACATAGAGCCCCAGTGCCACCAACAGCGCCTGGTATACATATTTGCGATACTT

AATAAGAATTAGTTGAAGAAATGAATAGGAAAGGGAGTCCCTTTAGATGGAGGAAGGGACTTTCTCAA

AAGGCCTCATGGAAGGAGAATGGCATTGAGGCTGGCTTACAAGAAGTGTGTCTTTTATAAAAAGAAGG

AAGGGCAGGGCTTCCAGGTGAAAGGCATAGCACAAGCAAAGGCAAAAAGACGGGTAACTGCTAGTTGT

TAAGGGCAGTGGCTGAATCGCTATACCCCTAGCAGTTCTACACCTAGGGGCCTGCGGGCCGCTGGGTC

TGCGAAGCTTGCAAGGCAACTGGCCCGCCCCCGCTCTGCGCCTGTCTCTCGGCCACGCCTATTGCTGC

AGGATGACGCGCACCTCTAGAACCCGCCCCGGAGGGGAGGGACGCAGGGAAGAGTCGCACGGACG
custom-character

ATGCCGCCTCCTCGGACGGGGCGCGGGCTTCTGTGGCTC

GGTTTGGTATTGTCTTCAGTGTGCGTGGCCCTGGGATCAGAAACTCAGGCGAACTCCACGACTGATGC

ATTGAACGTATTGTTGATAATAGTTGATGACCTGAGACCCAGTCTCGGCTGCTACGGTGATAAACTCG

TACGAAGCCCCAACATTGATCAATTGGCAAGTCATTCCCTCTTGTTTCAGAACGCTTTTGCCCAACAG

GCGGTTTGCGCACCGAGCAGGGTTTCCTTCCTCACAGGCCGCCGCCCTGACACTACCCGCTTGTACGA

CTTTAATTCATACTGGCGCGTCCATGCCGGTAACTTCTCTACGATACCGCAATACTTTAAGGAAAACG

GTTATGTCACTATGAGCGTAGGTAAGGTATTTCACCCGGGGATCAGTTCCAACCACACCGACGATTCT

CCTTACTCTTGGAGTTTTCCTCCATATCACCCAAGCAGCGAAAAGTATGAGAATACAAAAACTTGTAG

AGGCCCCGATGGTGAGCTTCACGCAAATCTGCTTTGCCCAGTCGATGTGCTCGATGTCCCAGAGGGCA

CTCTGCCGGATAAGCAATCCACGGAGCAGGCTATACAGCTGCTCGAAAAGATGAAAACTTCAGCGAGC

CCGTTTTTCCTCGCGGTGGGTTACCACAAGCCGCATATCCCGTTCCGGTACCCTAAGGAGTTTCAAAA

ACTTTATCCGTTGGAGAATATCACACTCGCGCCCGACCCCGAAGTCCCAGATGGACTTCCTCCGGTCG

CTTATAATCCCTGGATGGACATTCGCCAGAGGGAAGATGTACAAGCTCTCAATATCTCTGTTCCATAC

GGGCCCATTCCGGTTGACTTTCAGAGGAAGATTAGACAATCATACTTCGCCAGCGTATCCTATCTTGA

CACCCAAGTTGGACGCCTGCTCTCCGCGCTTGATGACCTGCAACTGGCAAACAGTACCATAATAGCCT

TTACCAGTGACCACGGTTGGGCACTCGGAGAACATGGAGAGTGGGCCAAGTATAGTAATTTTGACGTG

GCTACCCATGTACCATTGATTTTTTATGTTCCCGGCCGGACAGCTAGTCTCCCGGAGGCTGGAGAGAA

ACTGTTTCCATACCTTGACCCCTTTGATTCCGCGTCTCAGCTTATGGAACCGGGCCGCCAAAGCATGG

ACTTGGTTGAACTGGTTAGTCTCTTCCCGACGTTGGCTGGCCTTGCAGGGCTCCAAGTTCCACCGCGG

TGTCCCGTACCTAGTTTCCACGTTGAACTCTGTCGGGAGGGGAAGAACCTCCTTAAGCACTTCCGCTT

TCGGGATCTTGAGGAGGACCCCTACTTGCCAGGTAATCCTAGAGAGCTGATAGCGTACTCCCAGTACC

CACGACCGTCTGATATTCCACAGTGGAACTCCGACAAACCTAGTCTGAAAGACATTAAGATCATGGGC

TACAGTATTAGAACGATTGACTACAGGTATACCGTGTGGGTCGGCTTTAATCCAGACGAATTTCTCGC

GAACTTTAGCGATATCCATGCGGGTGAGCTTTATTTTGTTGATTCCGATCCGCTCCAGGATCATAATA

TGTATAATGATTCACAAGGAGGTGATTTGTTTCAACTTCTCATGCCGGACTACAAGGATGATGACGAC

AAGTA custom-character

The NEU1 protein sequence is:

(SEQ ID NO: 24)

MTGERPSTALPDRRWGPRILGFWGGCRVWVFAAIFLLLSLAASWSKAEND

FGLVQPLVTMEQLLWVSGRQIGSVDTFRIPLITATPRGTLLAFAEARKMS

SSDEGAKFIALRRSMDQGSTWSPTAFIVNDGDVPDGLNLGAVVSDVETGV

VFLFYSLCAHKAGCQVASTMLVWSKDDGVSWSTPRNLSLDIGTEVFAPGP

GSGIQKQREPRKGRLIVCGHGTLERDGVFCLLSDDHGASWRYGSGVSGIP

YGQPKQENDFNPDECQPYELPDGSVVINARNQNNYHCHCRIVLRSYDACD

TLRPRDVTFDPELVDPVVAAGAVVTSSGIVFFSNPAHPEFRVNLTLRWSF

SNGTSWRKETVQLWPGPSGYSSLATLEGSMDGEEQAPQLYVLYEKGRNHY

TESISVAKISVYGTLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NEU1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

NEU1-DNA

(SEQ ID NO: 25)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
ATCATGGTGAGTGACTCCCCTCTCTGCTGC

TCCACCCCCAACTCCCCAGAGGAACCCAATAACCCCAACGGGTCATGTCTTCCAGACCTCCATCCTGG

GGGCCTATGTCATCGCCAGCGGCTTCTTCAGCGTTTTCGGCATGTGTGTGGACACGCTCTTCCTCTGC

TTCCGTGAGTGACACCCCCAGCCACCTGTCCCCAACCTTAAAGTACTGAGCCGTTCAAGCATTTTTTT

TTTTTTTTGGAGATTTGGTGCTTCTAGAAAGAATGCCTTTGTGAGCTAAACGAACCAGAGGGAGCTTC

TTGTGACATCCTGAGGCCAGGCGTTTAGGGAAGAAGGAAGAGAGTGAGCCCCCAGGCCGGTAGGCTCT

CCAAAGAAGGAGCATTCTGATGGAGAGGTCTCTGCTATCTTCCCTAAGAAATCTCGGGTAGAAGTTAG

CCATTAGAGGCCAGGCATGGTGGCTCACGCCTGTCATGCCAGCACTTTGGGGGACCGAGGTGGGCAGA

TCACCCTGAGGTCAGGAGTTCGAGACCAGCCTGGCCCACATGGTGAAACCCCTCTCTACTAAAAATAC

AAAAAATTAGCTGGGCGCGGTGGCGGGCGCCTGTAATCCCAGCCACTTGGGAGGCTGAAGCAGGAGAA

TCGCTTGAACTCAGGAGGCGGAGGTTGCAGCGAGCCGAGATTGCGCTACTGCACTTCAGCTTGGGCGA

CAGCAAGACTCCGTCTCAAAACAAAGAAAAAAGATTAAAAAAAAAAAAGAGCCATTAGAGAGACTTCC

CAGCAGGTGGCTGTAGCGGCAGGGGATTTTCTTACTCTACAGCATGCATCCATTCAGGGTTTGCCAGT

CTCCTCCTAAGCGACTGACATGCATTTTTTCCGCTAATTCTTATCATCGCTCTATGCAACATAATATT

CCCGACCCCACTTCACAGGAGGAAACTGAGATTACATAACCTGCCCGGGGGTAAGGGTGGTGGTGCAG

CTTGGATTCCAAATCCCGCAGGCAGCTTGCCTCCCAGTCCCCGATTTCCTGGCCCCAGGGTCCGCTCT

AACCGGTCTCTGTTGCGGCTCAGTGGAAGACCTGGAGCGGAACAACGGCTCCCTGGACCGGCCCTACT

ACATGTCCAAGAGCCTTCTAAAGATTCTGGGCAAGAAGAACGAGGCGCCCCCGGACAACAAGAAGAGG

AAGAAGTGACAGCTCCGGCCCTGATCCAGGACTGCACCCCACCCCCACCGTCCAGCCATCCAACCTCA

CTTCGCCTTACAGGTCTCCATTTTGTGGTAAAAAAAGGTTTTAGGCCAGGCGCCGTGGCTCACGCCTG

TAATCCAACACTTTGAGAGGCTGAGGCGGGCGGATCACCTGAGTCAGGAGTTCGAGACCAGCCTGGCC

AACATGGTGAAACCTCCGTCTCTATTAAAAATACAAAAATTAGCCGAGAGTGGTGGCATGCACCTGTC

ATCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCAGAGGTTGCAGTGAGC

CGAGATCGCGCCACTGCACTCCAACCTGGGTGACAGACTCTGTCTCCAAAACAAAACAAACAAACAAA

AAGATTTTATTAAAGATATTTTGTTAACTCAGTAAATCTGTGACTCATTCTCTCCACGACGACAGGCG

GCCTTTTTTTTTCCGCGCCCGGCTCTTTAAAATCGGCCCCGCCCCTGTGACGTGTCCTGGTGCCGCGG

CCAATCAAAAAGCCCAATAAGGATGGTGCCAGTCCCTTCTTCACCCCAGCCAGTCCGCTTCCCGTTCG

GGTCACGCGCTCCGGGCCTCCAAGAGGGCCTCCAAGAGGGCCAATCGGAAGGGCAAGCTTCGAGATGC

TGCGTGATCACGTGGGAGGAGATGAGCTACTTGAAGACCAATTAGAGTCCGGGAAGCGCGGCGGGGCC

TCCAGACCGGGGCGGGCTTAAGGGTGACATCTGCGCTTTAAAGGGTCCGGGTCAGCTGACTCCCG
custom-character

ATGACAGGCGAACGCCCTAGCACTGCATTGCCTGACAGA

CGGTGGGGCCCTCGAATACTCGGGTTCTGGGGAGGGTGCAGAGTATGGGTTTTTGCGGCCATATTCCT

CCTGTTGAGCCTGGCTGCATCCTGGTCAAAAGCGGAGAACGACTTTGGGCTGGTGCAACCGTTGGTTA

CGATGGAGCAGCTCCTGTGGGTTAGCGGCAGACAGATCGGGTCAGTAGATACGTTCCGAATACCACTG

ATCACAGCCACTCCGCGAGGCACACTCCTTGCTTTTGCAGAAGCCAGGAAGATGAGCTCATCAGACGA

GGGCGCTAAATTCATCGCATTGCGGCGATCCATGGACCAGGGATCTACATGGAGCCCGACGGCATTTA

TAGTGAACGATGGGGACGTGCCGGATGGACTTAACCTTGGAGCGGTTGTATCAGATGTGGAGACAGGC

GTTGTGTTTTTGTTCTACTCACTTTGCGCACACAAGGCGGGCTGCCAGGTTGCTAGCACTATGCTCGT

ATGGTCCAAGGATGACGGCGTGTCCTGGTCTACGCCACGAAATCTCTCACTCGACATTGGTACTGAAG

TATTTGCACCAGGGCCGGGTTCCGGTATCCAGAAGCAACGGGAACCTCGGAAAGGTAGACTTATAGTA

TGCGGACACGGAACTCTTGAGCGGGACGGCGTTTTCTGTCTCTTGTCTGACGATCACGGGGCATCCTG

GAGGTATGGTAGTGGGGTTAGTGGGATACCCTATGGCCAGCCTAAACAGGAGAACGATTTTAATCCGG

ACGAGTGCCAGCCTTATGAACTTCCCGACGGCTCAGTGGTCATAAATGCGCGCAATCAAAATAACTAT

CACTGCCACTGTAGGATTGTGTTGCGGAGTTACGATGCTTGTGATACACTGCGACCGCGAGATGTGAC

ATTCGACCCAGAATTGGTGGACCCCGTAGTAGCGGCGGGGGCCGTGGTCACAAGTTCAGGGATAGTTT

TTTTCAGTAACCCTGCTCATCCCGAGTTTAGAGTGAATCTCACTCTTCGGTGGTCTTTTTCCAATGGG

ACCAGTTGGAGAAAAGAAACGGTACAACTCTGGCCTGGACCGTCCGGTTATTCTAGTCTCGCGACGTT

GGAGGGGTCAATGGACGGAGAGGAGCAGGCCCCGCAACTCTACGTCCTGTACGAGAAGGGGCGGAACC

ATTACACCGAGTCAATAAGTGTCGCTAAAATCTCCGTTTACGGCACATTGGATTACAAGGACGACGAT

GACAAGTA
custom-character

The SUMF1 protein sequence is:

(SEQ ID NO: 26)

MVPIPAGVFTMGTDDPQIKQDGEAPARRVTIDAFYMDAYEVSNTEFEK

FVNSTGYLTEAEKFGDSEVEEGMLSEQVKTNIQQAVAAAPWWLPVKGA

NWRHPEGPDSTILHRPDHPVLHVSWNDAVAYCTWAGKRLPTEAEWEYS

CRGGLHNRLFPWGNKLQPKGQHYANIWQGEFPVTNTGEDGFQGTAPVD

AFPPNGYGLYNIVGNAWEWTSDWWTVHHSVEETLNPKGPPSGKDRVKK

GGSYMCHRSYCYRYRCAARSQNTPDSSASNLGFRCAADRLPTMDDYKD

DDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SUMF1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SUMF1-DNA

(SEQ ID NO: 27)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
ATAGCTGGACCAGGAATCAAAGAAGTTCAG

GTCTCTGAAGCGCAGCTGACACAGCATGTGCTGAGACTGATATTTGAAGGAGGCGAACAAAGATTACC

GTTGACCTAGACCTTGACTATATATTATGCACAGTAAATACATACAACCTTGGTTAAGGCATTGACCT

TTTAGCTTCATCAATTTTGAAATGAGTATAGTAATAATACATTTCTTGCCAAGTGGTTGTAATCTCAA

ATGAGAAAATGTGTGAAAGGCCTTGGCAAACTGTAAAATAGTCAACAAGGAGAAAAGGCCTTTTTTTT

TTTTTTGAGAGATGGTCTCACTTTGTCACCCAGGCTGGAGTGCAGTGGCACAATCATGGCTCACTGCA

GCCTCTGCCTACCAGGCTCAAGTGATCCTCCTGCCTCAGCCTCCGAAGTAGCCAGGACCACCGGTGTG

CGTCACCATGGCCAGTTAATTTTCTTAATTTTTTGTAGAGACAAGGTCTTGCTGTGTTGCCCAGGCTG

GTCTCAAGCTCCTGGCCTCTAGCGATTCTCCTGCCTCGGCCTCCTAAAGTGCTGGGATTACAGGCTTG

AGACACGGTGCCTGGCTGGTCTTTTCTTTATGCTAAAAAAATTCAAACAGATGCTACATTAGAATAGT

GCAATAAACACCCAGATGCCCATCAACCAGCTATGACAGTTATCAACTCATGGCCAATCATGCTTCAT

CTTTAGCCAGACCCTGATTACCCATTTTTTGGGAAGCAAATCTTTGACTGCCTATATTTTTATCCATA

TATATATATGTGTGTGTGTGTGTGTGTGTGTGTGTATACCTCAGTGAGTGTGTGTGTACCTCAGTGAG

GGGATTCTTTTAAAAAATATAGCCACAAATACCATTATTACTCCTAAAAGCCTAAAAACAAAATTTAC

AGCAATTCCTTAATTTTATCAAATATTATAATTTGACTTAGTGGTTAAATTTCCCTGATTATCTCAAA

AATTTTGAACTCAGTAGGTTTGAATTAGTATTTAGATAAGGTTCACATATTGCAGCTGGCTGCTATGT

TTTTTTTTTTTTTTTTTTTTTCAGATGGAGTCTTGCTCTGTCCCCAGGCTGGAGTGCGGTGGCGCCAT

CTCGGCTCACTGCAAGCTCCACCTCCCGGATTCATGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTG

GGACTACAGGCGCGTGCCACCACGCCGGGCTAATTTTTTGTATTTTTTAGTAGAGATGGGGTTTCACC

GTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG

GATTACAGGCTTGAGCCACCGCGCCCGGCCTGCTATGTTGTTTTTTAATCTGTAAGTTTCTCCTTCAT

CTTCTTTTTGTTTTGGTTTTGCATTTTGTTCGATTACGGAACTGTAGAACAGTGGTTCTTAAACTTAA

GTGTGGATTAGAATCATCTGGAGAGCTTGTGAAACCCTGGATTGCTGTGTCCAGTCCCCACGGATTCT

GATTCCGTATTGTATTTCTCTTTTTTTTTTGAGACGGAGTCTTGCTCTGTCGCCGAGGCTGGAGTGCA

GTGGCGGGATCTGGGCTCACTGAAACCTCCGCCTCCCAGGTTCAAACGATTCTCCTGCCTTGGCCTCC

CGACTAGCTGGGACTACAAGCGCGCCATTACTGGGTCTTTGTGAGGATTAAATGAGATTTTAAAAAGT

GAAGTGCTTAGCATAGTACTCTGGCACTTACCAAATGCCCAGCAAATTTGACTGTTATTTTTCAACCA

AGAAATCATAAAGGGGTGCACGGTCTGTGGAAGGCCTTGAGTTTTGTGGAGTTTTGTGTTTTGCTGCG

TTTTGACGTTAGCACAGGCAAGCAGCAGCGCCAAAGAAGTACCTGAAGAAAGGTGAAGAGCAACTCTC

CTGGTCACTTCGTAAGTCAGCTCAAAATTCTGCCCCTTTAAGGAGGGCTCAG
custom-character

ATGGTTCCAATCCCCGCCGGGGTGTTCACCATGGGGACGGACGACCCACAGAT

TAAGCAGGATGGCGAAGCTCCAGCGAGAAGAGTCACCATAGACGCTTTTTACATGGATGCTTACGAAG

TGTCTAACACGGAGTTTGAAAAATTTGTTAATAGCACAGGTTATTTGACGGAGGCGGAGAAGTTCGGT

GACAGCTTTGTCTTCGAGGGCATGCTTTCTGAACAGGTGAAGACTAACATTCAGCAGGCAGTTGCAGC

GGCACCTTGGTGGCTCCCAGTTAAGGGGGCAAATTGGCGACACCCAGAGGGACCAGACTCTACTATAT

TGCACCGGCCTGACCACCCGGTTCTTCACGTATCCTGGAATGACGCCGTTGCCTACTGCACCTGGGCA

GGAAAACGACTGCCGACCGAAGCAGAGTGGGAGTATTCTTGTAGAGGAGGACTGCATAATCGGCTTTT

TCCCTGGGGTAACAAGCTTCAGCCCAAAGGCCAACACTATGCTAACATCTGGCAAGGGGAATTTCCCG

TCACGAACACTGGGGAGGACGGATTTCAGGGGACCGCACCTGTAGATGCGTTTCCCCCCAACGGGTAT

GGTCTCTACAACATCGTCGGTAATGCCTGGGAATGGACCAGCGACTGGTGGACGGTGCACCATTCTGT

TGAAGAAACATTGAATCCCAAAGGGCCACCAAGCGGAAAGGATCGAGTGAAGAAAGGCGGATCTTATA

TGTGTCATCGGTCCTACTGCTACCGGTATCGGTGTGCTGCTCGCTCTCAGAATACACCCGACTCAAGC

GCAAGCAATCTTGGTTTCCGGTGTGCGGCCGATCGCTTGCCGACAATGGATGACTACAAGGACGATGA

CGACAAATA
custom-character

The GAT1 protein sequence is:

(SEQ ID NO: 28)

MATNGSKVADGQISTEVSEAPVANDKPKTLVVKVQKKAADLPDRDTWKG

RFDFLMSCVGYAIGLGNVWRFPYLCGKNGGGAFLIPYFLTLIFAGVPLF

LLECSLGQYTSIGGLGVWKLAPMFKGVGLAAAVLSFWLNIYYIVIISWA

IYYLYNSFTTTLPWKQCDNPWNTDRCFSNYSMVNTTNMTSAVVEFWERN

MHQMTDGLDKPGQIRWPLAITLAIAWILVYFCIWKGVGWTGKVVYFSAT

YPYIMLIILFFRGVTLPGAKEGILFYITPNFRKLSDSEVWLDAATQIFF

SYGLGLGSLIALGSYNSFHNNVYRDSIIVCCINSCTSMFAGFVIFSIVG

FMAHVTKRSIADVAASGPGLAFLAYPEAVTQLPISPLWAILFFSMLLML

GIDSQFCTVEGFITALVDEYPRLLRNRRELFIAAVCIISYLIGLSNITQ

GGIYVFKLFDYYSASGMSLLFLVFFECVSISWFYGVNRFYDNIQEMVGS

RPCIWWKLCWSFFTPIIVAGVFIFSAVQMTPLTMGNYVFPKWGQGVGWL

MALSSMVLIPGYMAYMFLTLKGSLKQRIQVMVQPSEDIVRPENGPEQPQ

AGSSTSKEAYIDYKDDDDK

GAT1 DNA

(SEQ ID NO: 29)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AGGTCGGGTCTGCTCAAGTTCTGCAAAGAT

GGCTGCCAACACCTCTATGCTTAGGAGCTTTGGTGGAGATTGAGTTTCTGTTTGACAATAGTTTTAGC

AAAAGTCCCAGACAGAGTTCTCATTGGCCCAGCATATGTCACACGTCCCCTCATTGAGGTCAGAGTGA

TGTGCTCTGATTATCTGTGCCCTGGGTCACATGTCTGTCTCCAGGAGGAGGGAGCCCCACCCAACCAT

ATTGAATATGAGTGAAGGAGGGGAAGTTTCCCAAATGAAAATTGAGGTTCTGTCACCCAAAGAAGTTG

AAATGAATGTCAGGCAAGCAAAAGTAGCCTTCATTTTTGCTACCCTTGTATCTCCACTCAAAGCTATG

CCCCACATCTCCATCCAGACAGCTCCTACTCATCCTTCAGACCTCAGTTCAAATGGCGCTTCCTTGAG

GAAACCTTCCCAAACCATCCCACACTAGACTGGAATCCCCTGCTGGACTAGAATCCCCTGCATGTGTG

CTCCTGGCAGAGCTTGTCATTCTGGGTTTGTGCGGTTATTTGATGAAAGCCTGTCTCCCATACTGGAC

TGGCATCACCTTGAAAGCTGTGGCCTGTCTTGTCCATCGCTCTGTCCCTGGAGCCTAGGACAGTGCCT

GGCACACAGGTGGAACTCGGGAAATATTTATTTGAAATACCAACGGAAGTCCACAGCACATATGACCT

GGTGATCAGTGGTGGGAGGTGAATGGGTCAAGAAAGACACCAAGATTCCCTGCTCATGAGTGAGAGTG

TGGGGAAACAGAAGAAGTCAGGGTGACCTTGGTGAGCACTGCCCTGGGGGACTCGAGGATGGATGAAA

GCAGGGAGGAGGCCAGATTAGGTGGGGTAGAGGACCTGAGGTCCATCAGCAAAGGCCATCCCTGGGGA

CAAAGAGAGGAGGGGAAGAGTAGGTCTGGGCTGGAGAGAAGGAATCTTTTCTCTGAGTTCCTGGGGAC

CCCAGAGGGAAGGGCAGATGTGGCCCCATTCCCAGAAGCCTTTATAAAAGAGGGTGGGGAGGTCAGGC

CTTGGCAAGGACAAGGGAAGGAGTCCCTACGTGCTGGATTGGGATTGGCTGGAAAGGGGACTTCTCTG

GGAGAATCCCTCAAACCTCAAGAACTGAGAGAAGGGTGTCTGGGGCTCCTGCCACCATCCCTGTTTCC

CTTTTAAGTAATCTGTTTCCCCATCTGTCCATCCATACACACAGCCACTTGTGTCTCCATGACCAACC

GCTGGCAGTGGAAGGGTGTCCTTCCCACCCCCACTCTTACACACACTCCCAGCTGGTACCCAGAGCCT

GGTCACCCCAGGCCAGGCCTGTGTTTCCAGGTGTAACGGGCAGCAGACGCTGCCCTAGGACTAGAGCA

GGGAGGGGGCACGGGCCCACCCCAACCCACAGCGACCCACAGAGGGCGAAAAGAGGACGACCGCAGAG

AGAAACGGAAAGGACAGGCCAACGGAAGCAGTACTGCAAGGCTGGAAGGAGAAAAGCCAGGAGGGGAG

TGCTTGCTGTGAAAGACAGGGAGACAGAGACCAAGACGGACAGGCAGACAGGCTGGTGACCCAGGATG

AGGCCGGAAAGAGCCATCAAAGGAAGGAGAAGGAAGGAGAGAGATTGGAGCGGGACGGCGGGGCAGGC

GAGGGAAGGAGGGGGTGGGGAGAGGGAGGGAGGAAGAGAGGGGAGAAAGAGGGAGGAAGAGAGGGGAG

AAGGAGGGAGAAGAGAGCGGGAGAATGCGAGAGGAAAGAAGGGAGAGGGGAGGCGTAGAAGGGGAGAG

GAGGTGAAGGGAAAAGGAGAGAGCCTGCTGGCGGCGAAGCTGCAAGAGGCAGCTGCGGAGGGAGCGCG

CGGCGGGCCTGGGGGAGCGCTGGGCGGGGGCGGGCGGTGCGGGCAGGGCTATACCCGAGCTGGGCGGG

CTCCGGGCGCCGCGGGCCCTGCCCTCCCCCTCCATCCCTCCGGACTCGCTCCCCCCTCCTCTCCCTTC

CCCGCGACCCTCCGCC
custom-character

ATGGCAACTAACGGTAGTAA

AGTCGCGGACGGTCAGATCTCCACAGAAGTTTCTGAAGCGCCGGTCGCAAATGATAAACCAAAGACCC

TCGTAGTCAAGGTACAGAAAAAAGCTGCTGACCTTCCTGATCGAGATACCTGGAAGGGCAGGTTTGAT

TTCCTCATGTCATGCGTTGGGTACGCCATCGGCCTCGGAAACGTATGGAGGTTCCCCTACCTGTGCGG

TAAGAATGGTGGCGGAGCCTTCCTGATACCATACTTTTTGACTCTCATATTCGCAGGCGTGCCACTCT

TCTTGCTCGAGTGCAGCTTGGGCCAGTACACGTCTATAGGCGGCTTGGGCGTATGGAAGCTGGCGCCC

ATGTTCAAAGGTGTTGGCTTGGCCGCTGCTGTACTGTCCTTTTGGCTGAACATTTATTACATAGTGAT

CATATCCTGGGCAATTTACTACCTCTACAATTCTTTTACGACAACACTGCCCTGGAAGCAATGCGATA

ACCCATGGAATACGGACCGATGCTTTTCCAACTATTCAATGGTAAACACCACGAATATGACGTCTGCG

GTAGTCGAATTTTGGGAACGGAACATGCACCAGATGACCGATGGTCTCGATAAACCGGGTCAGATTAG

ATGGCCACTCGCAATAACTCTTGCCATCGCATGGATACTCGTATACTTTTGCATCTGGAAAGGTGTCG

GATGGACAGGCAAAGTAGTCTATTTTAGTGCTACATACCCTTATATCATGTTGATTATACTGTTTTTC

AGAGGAGTCACACTTCCTGGGGCGAAGGAGGGCATTCTCTTCTATATCACGCCAAACTTTCGAAAGCT

GAGTGACTCAGAGGTTTGGCTCGATGCTGCAACTCAGATATTCTTCTCATACGGCCTTGGTCTGGGTA

GTCTCATAGCCTTGGGTTCCTACAATTCCTTTCACAATAACGTGTACCGAGACAGCATTATAGTATGT

TGTATTAATTCTTGCACTTCAATGTTCGCCGGTTTCGTCATTTTCAGCATTGTCGGATTTATGGCGCA

TGTTACCAAAAGGAGCATTGCGGATGTGGCGGCTAGTGGGCCAGGACTCGCTTTCCTCGCCTACCCAG

AAGCAGTTACTCAGTTGCCGATTAGCCCACTGTGGGCTATCTTGTTCTTTTCTATGCTCCTTATGCTT

GGGATAGATTCCCAGTTTTGCACGGTAGAGGGTTTCATAACGGCACTTGTCGATGAATATCCGCGACT

CCTGAGAAATAGACGCGAACTCTTTATAGCAGCGGTATGTATAATCTCATATTTGATAGGCTTGTCAA

ACATAACACAAGGGGGAATATACGTTTTCAAATTGTTCGACTACTATAGTGCCTCCGGGATGTCACTT

CTTTTCCTGGTATTTTTCGAGTGCGTTTCAATCAGTTGGTTTTATGGCGTGAATCGATTTTATGACAA

CATTCAGGAGATGGTAGGAAGTAGACCGTGCATATGGTGGAAACTCTGTTGGTCTTTTTTCACGCCCA

TCATCGTGGCCGGCGTGTTTATATTTAGCGCAGTGCAAATGACTCCTCTCACTATGGGGAACTATGTC

TTCCCCAAATGGGGCCAAGGGGTAGGCTGGCTCATGGCGTTGAGTTCCATGGTCCTTATTCCAGGTTA

TATGGCTTACATGTTCCTGACACTGAAAGGGAGTCTGAAACAACGGATTCAGGTGATGGTTCAACCTA

GTGAAGATATTGTCAGACCTGAGAACGGTCCCGAGCAACCTCAGGCGGGAAGTAGTACCTCTAAGGAG

GCTTATATAGACTATAAAGACGACGACGATAAATA
custom-character

The FIG. 4 protein sequence is:

(SEQ ID NO: 30)

MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVII

DDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEG

YYIVLITKRRKMADIGGHAIYKVEDTNMIYIPNDSVRVTHPDEARYLRIFQN

VDLSSNFYFSYSYDLSHSLQYNLTVLRMPLEMLKSEMTQNRQESFDIEEDEG

LITQGGSGVFGICSEPYMKYVWNGELLDIIKSTVHRDWLLYIIHGFCGQSKL

LIYGRPVYVTLIARRSSKFAGTRFLKRGANCEGDVANEVETEQILCDASVMS

FTAGSYSSYVQVRGSVPLYWSQDISTMMPKPPITLDQADPFAHVAALHFDQM

FQRFGSPIIILNLVKEREKRKHERILSEELVAAVTYLNQFLPPEHTIVYIPW

DMAKYTKSKLCNVLDRLNVIAESVVKKTGFFVNRPDSYCSILRPDEKWNELG

GCVIPTGRLQTGILRTNCVDCLDRTNTAQFMVGKCALAYQLYSLGLIDKPNL

QFDTDAVRLFEELYEDHGDTLSLQYGGSQLVHRVKTYRKIAPWTQHSKDIMQ

TLSRYYSNAFSDADRQDSINLFLGVFHPTEGKPHLWELPTDFYLHHKNTMRL

LPTRRSYTYWWTPEVIKHLPLPYDEVICAVNLKKLIVKKFHKYEEEIDIHNE

FFRPYELSSFDDTFCLAMTSSARDFMPKTVGIDPSPFTVRKPDETGKSVLGN

KSNREEAVLQRKTAASAPPPPSEEAVSSSSEDDSGTDREEEGSVSQRSTPVK

MTDAGDSAKVTENVVQPMKELYGINLSDGLSEEDFSIYSRFVQLGQSQHKQD

KNSQQPCSRCSDGVIKLTPISAFSQDNIYEVQPPRVDRKSTEIFQAHIQASQ

GIMQPLGKEDSSMYREYIRNRYLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for FIG. 4 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

FIG. 4-DNA Sequence

(SEQ ID NO: 31)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GTAGCAGCTGCTATTAGTGCCTCCCCCATA

TCCACTTGACATACACCTTTTCTATGCACGACCAGCCCAACTTCCAAAATGTTAGCATGTGCGACTTT

TTGCCTAAGGGCTTTCTCTGGCTGCCAGAACCTACTCTCCCTGAACACAGGGTAGACTGGAAGTTCTA

GGGCATCAATGTTCTGCCCTATCAGGCTTCATCCAATAACTGATGGAAGTTGGCGAATAAATACTCCA

GCTTCCTTGCCCCTCAAGAGGGGATAACTGAGACATGCCTCCCAGTATTCCCTAGTGAATTCAGCCCA

CAGAGAAATTTCTCTGGTAATATTTCCTTTATTAGTTTTCTTCCCCTCCCTGCTGCTGTTTCCTGGGA

TTACGTCTCATATAAACAACCTGCCTTCAAAGTTTTGTCTTAGGATCTGATTCCGGGTGAAATAAACT

AAGATAAAGTTAAAATGGAAGTGCTAAACTATAATAATTGAAAACTAGAATCCTTCAGGTATTTTAAG

AGTTGCTATCCTAGATAAAAACACTGTGCAAACATTTAACTAATATTCAGAAGAGTTGGTTTCATTAT

GAAACAGAACACAGCTAACTATTTTTCCCAGTTAAAAGATCCAAGTCCAAAATGCCAGAACGGACACG

GCCATCCTTCTAGTTCTTAATAAAAGGAGTACCAAACTACAGGGGGAAAGAAGCGCAAAATAACATAG

ACTTAAGTATTTCTTTACAATTTTTGTAATTTCTCAAATTTTAATTTACAATATGATCTTTGGTATTA

CATGAATGTTATCTGGGTATGCTATAATTCTATAATTTTTTTTTAAAGTTTCCTTACACTTAGCAGTT

GAGAAGCCCTCTAGCAGAGGTTTCTGAGGTTTAGAGGTTTCCTGGGAAACCTAGAATTGCCGCCTAAG

ATAGGATAGCTGCCTCTCCCCTACATCTTATACTCTTGCAGTAGGTGTTCAGTAAATATTTGTGGAAT

AAATACTTCAGTCGTTGAAAGGAGACGTGGTTTTAAAAAGTGGATTTACAAAGAGACCGTTTTGCAAG

AAAAGAAGCTGGTCTGGGGGTCCCCGCAGGAGGCGGGGTTCCGTGCAACAGATACCAAGATGCCTCCA

GGGCGGACCACGACCCAGCGGGCCGCCGGAAGGCTCCTTACCTGGCCGCAGCCGGACCCTCCTCAGGG

AAGCAACTGCCTCCAGGGACTCCGCGGGGCTGTCGGGCGGTTGCCGGGGAGACCTCTGGCCGCCACGC

ACCTGCTGCTTGGTGGGGCGGGGCCTCGAGAGGCGGGGCTGTAGTTCTTTGTCATTTCTTTTCCAATT

CGAAATAGTCACTTTTGTACCTAATTTGGCATTTATAATTATAATACACTCATTTTCACAACTATGGA

AGAGAGGGTACGCGCATGCCCATTTATGTCGCACACATGAAATGAAGAAACCTCATTTCAAGCGCGGC

TCCGCCACACTGCGCTAGTCTCTGTCGACAACTTCAAGTGGCTAGCCTCACGCACAAACGTGTGGCAA

AGCCACACTTTCCAGCTTTAGGTGATTTTAAAACAATTTCTTGGGCCACACAGCGTAGGTACAACATG

GATTAGAGGTGAGGGGAAAACTGACACTCAGTGAAGGACCGTCAGAGGGCCGGCTTCCAGGAAAATGG

GCCGCAGCAGGCAGGGAAAACACAAGGATCTATCCTGCAACTCGGAGAACCCTTTTCAAAAGAAGCTA

CCCAATCCCAAACCTTCCGCTTTTTTCCAAAGAGAGGGAGGAGATAAATAGACTCAATTAATCCGTCG

ACTTTTTCTCCGCCCATGTTTTCCTCCAATCCTTACCAAAGATGGTGCCCTTCGCTTCCTCTCTCGGC

AGCACGCAGGTCCCGGGAGCCTCTACCCGACCTCTCTATGATACGTCCTCCAGCCCCGCTCCCGACGT

GAGGGGCGGGGCTTGCCTGGAGGCGGGGCGCAGGGATCCGGAAACACC
custom-character

ATGCCCACGGCAGCGGCTCCAATAATCTCTTCCGTTCAAAAGCTTGTTTTGTATGA

AACTCGCGCGCGGTATTTTCTTGTAGGTTCAAATAATGCGGAAACAAAGTACAGAGTACTGAAGATAG

ACAGAACTGAGCCTAAGGACCTTGTCATAATCGATGATAGACATGTTTATACGCAACAGGAAGTGCGG

GAACTCTTGGGCAGATTGGATTTGGGGAATAGAACAAAAATGGGGCAGAAAGGTAGCTCTGGGTTGTT

CCGAGCTGTCTCAGCTTTCGGCGTAGTAGGCTTTGTGAGATTTCTGGAGGGCTATTACATAGTGCTTA

TTACCAAAAGGCGCAAGATGGCGGATATAGGCGGCCATGCGATTTACAAGGTTGAGGATACAAACATG

ATATACATACCAAATGATTCAGTGCGAGTCACCCATOOTGATGAAGCTCGCTACCTGCGCATATTTCA

GAATGTCGATCTGTCTAGTAACTTCTATTTCTCCTATAGTTATGATCTTAGTCATAGTCTCCAATATA

ATCTCACCGTCCTGCGGATGCCCTTGGAGATGCTCAAATCCGAGATGACACAGAACCGACAAGAAAGC

TTCGATATTTTTGAAGACGAAGGTTTGATCACACAGGGAGGTAGCGGTGTATTCGGAATTTGTAGTGA

ACCCTATATGAAGTACGTATGGAATGGCGAGCTCCTGGACATTATAAAAAGCACGGTCCACAGAGACT

GGTTGCTTTACATCATTCATGGCTTCTGCGGCCAGTCTAAGTTGCTGATTTACGGGCGGCCTGTGTAC

GTAACTCTGATCGCAAGGCGATCTTCTAAATTTGCGGGCACCAGATTTCTCAAGCGAGGCGCCAACTG

CGAGGGAGACGTAGCTAACGAAGTTGAGACTGAACAAATTCTGTGCGACGCGTCCGTTATGAGTTTTA

CAGCAGGTTCCTACTCCTCCTATGTACAAGTACGGGGCTCAGTTCCTCTCTACTGGAGTCAAGACATT

AGCACTATGATGCCCAAACCCCCAATTACCCTCGACCAGGCCGACCCGTTCGCTCACGTTGCGGCCCT

GCATTTTGATCAAATGTTCCAACGATTCGGCAGCCCGATTATCATTCTGAATCTTGTGAAGGAGCGGG

AAAAGAGGAAGCACGAGCGGATCTTGTCTGAGGAATTGGTGGCAGCCGTGACATATCTGAACCAATTC

CTGCCACCGGAGCACACGATAGTATATATTCCTTGGGACATGGCTAAGTACACAAAATCTAAATTGTG

CAATGTGTTGGATCGCCTTAACGTGATCGCGGAAAGCGTAGTCAAGAAGACAGGTTTTTTCGTAAACA

GGCCCGATTCATACTGTTCAATTCTCCGACCTGACGAGAAATGGAACGAACTGGGGGGATGCGTGATA

CCTACTGGTCGCCTGCAGACTGGTATTCTCAGGACGAATTGTGTAGATTGCCTCGATCGGACGAATAC

AGCGCAATTTATGGTAGGGAAGTGCGCGCTGGCCTACCAGCTGTATTCACTGGGGCTGATAGACAAGC

CGAATTTGCAGTTCGACACCGATGCGGTGCGCCTCTTTGAGGAGCTCTATGAGGACCATGGAGATACA

CTCAGTCTCCAGTATGGAGGGTCACAACTCGTACATCGAGTTAAAACATACAGGAAGATCGCCCCATG

GACACAACATAGTAAAGATATTATGCAAACCTTGTCCAGATATTATTCCAACGCCTTCAGCGATGCCG

ATAGGCAAGATTCAATCAATCTCTTTCTGGGGGTGTTCCATCCCACTGAAGGTAAGCCCCACTTGTGG

GAGTTGCCTACAGATTTTTACCTTCATCATAAGAACACCATGAGACTGCTCCCAACACGGCGGTCTTA

TACGTACTGGTGGACACCTGAAGTTATTAAGCACCTCCCCCTCCCGTATGACGAGGTGATCTGCGCGG

TTAATCTCAAAAAATTGATTGTGAAGAAATTTCATAAATACGAAGAGGAAATTGATATCCATAACGAA

TTTTTTCGCCCATACGAACTGTCCTCTTTTGATGATACATTCTGTCTTGCCATGACTAGTTCTGCGAG

GGATTTTATGCCTAAAACGGTCGGAATCGACCCGAGTCCATTTACCGTTAGGAAACCTGACGAGACGG

GGAAGTCAGTATTGGGGAATAAGAGCAACCGAGAAGAGGCGGTGTTGCAGCGGAAGACCGCAGCTTCT

GCTCCTCCGCCCCCATCCGAGGAGGCTGTGAGTAGCTCTTCAGAAGACGATTCCGGCACCGACAGAGA

GGAAGAGGGATCAGTTAGTCAGAGAAGCACACCGGTGAAAATGACTGACGCGGGCGACTCCGCTAAGG

TAACTGAAAACGTCGTGCAACCAATGAAAGAGCTCTACGGTATCAACCTCAGCGACGGCCTTTCAGAA

GAGGACTTCTCTATCTACAGCAGATTTGTTCAACTCGGTCAAAGCCAACACAAGCAAGACAAAAATTC

CCAACAACCCTGCTCAAGATGCTCCGACGGCGTAATTAAACTGACTCCGATTAGCGCGTTTTCACAGG

ATAACATTTACGAAGTACAACCTCCACGAGTTGACCGGAAAAGTACGGAGATATTTCAGGCTCACATC

CAGGCCTCTCAAGGAATCATGCAACCCCTCGGAAAGGAGGATTCCTCAATGTACAGAGAATATATACG

CAATCGATATTTGGATTACAAAGATGACGACGACAAGTA
custom-character

The CLN5 protein sequence is:

(SEQ ID NO: 32)

MAQEVDTAQGAEMRRGAGAARGRASWCWALALLWLAVVPGWSRVSGIPS

RRHWPVPYKRFDFRPKPDPYCQAKYTFCPTGSPIPVMEGDDDIEVFRLQ

APVWEFKYGDLLGHLKIMHDAIGFRSTLTGKNYTMEWYELFQLGNCTFP

HLRPEMDAPFWCNQGAACFFEGIDDVHWKENGTLVQVATISGNMFNQMA

WVKQDNETGIYYETWNVKASPEKGAETWFDSYDCSKFVLRTFNKLAEFG

AEFKKNIETNYTRIFLYSGEPTYLGNETSVFGPTGNKTLGLAIKRFYYP

FKPHLPTKEFLLSLLQIFDAVIVHKQFYLFYNFEYWFLPMKFPFIKITY

EEIPLPIRNKTLSGLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN5 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN5 DNA

(SEQ ID NO: 33)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
CTTGGTTATGTCAGTTCCTGTGTGTAGACA

GTAAGAAAAAAAAAGCCATGCTATGTGTGACATTTTTTTCCAATGTTTATTTCCCACCAAAAAGTAAA

TGCATTTTAACCCATTCTGTGGTTCACTGTAGCTTAAGGAAACCAAGCATATAGATGCATTAGTGATT

TTGTTTATATTATGTAAAATGTAACGATCTATCTTAGAAATACCACAGTTTGTATTTTTCTTTAAGGA

GTAAAGATTTGTCTTTAAAAATAACTTGATATTTTCCTGGCTTTCATTTAATACAATGGAAAATAAAG

TATTACACGAAAAAAAAATTTTTTCTTAGAGACAGTATCTCATTATGTTACCCAGGCTGAAGTGCAGT

GGCTATTCACAGGCACGATTATAGCTCACTATAGCCTCAAAGTCCTGGGTTCAAGCCTCCTGAGTAGC

TAGAACTTCAGGTACATGCCACCTTGCCTGGCTTCCTGCTTTCTTATTCACTAAGAAACTTTGTTCTC

TAAAATCATAGATTAGAGACAACTTCGTGTTTGAAATTACATCAGTAACAATAAAATATCCCACCTTT

GCTTGAAGGACCTCAGTCATTCCACACAGAGAATTGGCCTCAATTTACAACCCAGATGTCAAGCTTCT

GATAAGGGGTTTCCAGACACAAAACTCCATCGCTATTTTAACTTCATAGTCTCCAAGGAAATAGGCCC

TTCATCCACTTTGCAGTCTAGACCTAGAGCCTGTGTGTTGATGGCAGCAGCAGGCCGTCTGGAGCAGC

CACTACCATCATTGACATACAGCCTTGTTTTGCTTTGAGTCTACCAAAATACTGCTTATTTAAATTTC

ATCTCAACTCCACACTTCCCCAGAATCCTATCACTCTATCTGGGGAGATGCCATGTGGTCCAGGCAGT

CTTAGGCTGAATGGGCAAGGATCCAAGGGAAACCAATTAGATTGAAATTAGTTCTGTCTGTGGGCCCT

CAAGATTTAAAAGCCATGGACAAGGGGGAAGCAACCAGTATCGACCAGCGATAATCTATGAGCACCTT

CAGCTTGGGGTGTGGGGTCATAGACAAAAAGAATGGGGTTTAATCAGTGTTCCCATCCAAGGCAAAAC

CAGACCAGAAGAATGGGAGCTACCAGGAGGCTGAGTTAAGACCAATACTAGGGCCAGGCATGGTGACT

ACAGCCTGTAATCCCAGCACTTTTGGAGGCCGAGGCAGGTGGATTACTTGAGGTCAGGAGTTCGAGAC

CAGCCTGGCCAACATGGTGAAACCTCGTCTCTACCAAAAAAAAAAAAAAAAATTACAACTGGCACACA

CTTGTACCCAGCCACTAGGGAGGCTGAGGCAGGAGAATTGCTTGAACCCGGGAGGCGGAGGTTGCAGT

GAGCCGAAATCACATCACTGCACTCCAGGCTGGGTGACAGAAGGAGACTCCGTCTCCAAAAAAATAAA

AAATAAAAACCAATACTAGGAAGTGCTTTCTTACCATGAAAGCTCCCTGCACACAGAATGAAGAGACA

GATGGCAGAAGCAAGACCAGAGGCCTCCACCACTGAACAAGGTCAACCTGAATTTGTTTTTGTAGCTC

TGGGAAGTCCTGAACTGAATGGGAGGTTCTACTGTGGCCCTCTACTAACAGTAGATGGAACCTGGAAC

CATCTACTGTTAATTGTCCTTTTAGTAGCCAAGACATGAAGTACCTATCTCCCTTCTTTGTATTTGGT

GAAAAGATTTGAACTCGAGCCATCTCTGCTAAAGGCATGACTTTAGTCACCCCACTGCAGTTGCTTCT

CTTTGCCTCCAAGAAAGTCCAATCTGATGGGCAGATTGTGCTTGCAGATGACTGGATTAAACTGCAAA

TATCTCATGAAGCTGCTGCCTGCATCACCGCTCTCCAGGCAGCCACGGAGGCTCTGGTTGTTGAGGCC

ATCTACTGTGGCCCTCATACATCATACTGTGTATGGTTCCAGGATTTGTAAATGCTCTAATCAATGTT

TTTTTTTTTTTTTAAAGCTGTTCCTGCTGATTGCTTTTTAAGCTAGGCTCAAGTGTGGGGCCACGGAA

TCCTTCAGGTGCCCTTCAAATCAGACATTACATTTCAGCTCTCAGGGCTAGAATGCTTCCCCCTCTTA

TCTTGGGCAGGTCTTTGAAGAAGCCAGTTTAGCCTTGGTAATTTTGAATTTGGCCATAGTATACGGAG

GAGAGCTAGGTAGCTATCAAAACGCTTAGACAAACGTATGGTAAAATGCAGCCCAGCCTGAACCTCCG

CAAAACCCCCAAACCTGGAGCAGCAAGTGGGCAAAGGAGTGTGTGTTTGGGGCAGGGTACTGAGTCCC

ATATGTAATCAAGAGACCTGGAGGGCCCAAGGAAGTCAGTGACACCCCCACAAGCTACATATCCTCCA

ATGGATTGTGGTGGTCATCTCCGGCTACCGAAGCCACCTTGCTTATTCCCATAGGCTTACAAACATTA

TGATGCTTCACACGAGTTGTGGGTGAAGTGAAGGAATTGGAAAGTCCCGGTCTAAGGCCCTGCAAAAC

TGCTGTCTGGTAAAAACAAGTGACTATGGCAAGGCCCTGAATGTACTACGTATAGACTTAAGTCAGTA

TTTGTGCCTAACAGCAAAGCATGCCACAAGAGGCTCCTCAAAAGCCGGGTAATTGATGCCATTGTTTT

CTTGACCTAGTTGAAGAGTCAAAGAAGAGAAGGTGATGCAGAAACTTCTTTCCAGTGAAGTGACAGAT

CCAAGCAAGGAACACCTGCCTGTGAGGGGAGCGGTAGGGGAGGGGGTAGATTCGGCAGCACTCGGGTA

GTGGCAGGGACCACATATTGTCGGTGTTAACCACTGTTATCACTGGCCCAGGTCGAGTGAGGACGAGT

CATTTCCCCACTAAGCACTTGGGGAGTGGCAGGGACCACATATTGTCAGTGTTAACCACTGTTATGAC

TGGCCCAGGTCGGGTGACGACGAGCCATTTCCGCACTATTGTCCCTTCTTCCTCACTGCACCCCCAGC

CCTGCACCCTCAGCTCCAAATACACATTCTCGTTCACTCAACGTTTGTTGACACCTAGCGTGGGCCCT

GTGGGATGGGGTAAAAGTTCGGTGTTGGGAGGAGCCCCGGTGACAGATTTTTGGTTTTGGTGGTGGCT

TTTGGGCAAGGACAGGTCAATTCATAAAAGATGACGCCCCAGGTCTGGATCGAATTCTCCTGGGAGCC

AGACCAAAGCACCTTCCTGGACTGCAAAGTGTGGAAGCCGCCGCGGGCCGGGCGCGGGGAGGTGTCAT

GCGCCGGAACCTGCGCTTGGGGCCAAGCTCTGGAGCTGACGCGCAGGGGCAAGGCGCCCCGCGTCCCG

GACTGGCGGCTCCGCGCATGCTCCTCCCACCGGCGTCGCAGGCCTCGAGAGGCTCCGG
custom-character

ATGGCTCAGGAGGTCGATACAGGAGAAGGGGGAGAGATGGGGAGGG

GAGCGGGAGCGGCGCGAGGCAGGGCAAGCTGGTGTTGGGCACTCGCACTGCTCTGGCTGGCGGTTGTC

CCGGGATGGTCTAGAGTGAGCGGCATTCCAAGTAGGAGGCATTGGCCAGTGCCCTACAAACGATTTGA

TTTCAGACCCAAGCCAGACCCGTACTGCCAAGCAAAGTATACATTCTGCCCCACTGGCAGCCCCATCC

CTGTGATGGAGGGGGATGATGATATAGAGGTCTTTCGGCTCCAAGCCCCAGTATGGGAGTTTAAATAT

GGAGATCTCTTGGGCCATCTGAAAATTATGCACGATGCGATCGGGTTTAGATCAACATTGACAGGCAA

AAATTACACCATGGAGTGGTATGAACTCTTTCAGTTGGGAAACTGCACTTTTCCGCACCTTCGACCTG

AAATGGATGCCCCTTTTTGGTGCAATCAGGGCGCGGCTTGTTTCTTTGAGGGTATAGACGATGTACAC

TGGAAGGAGAATGGCACACTTGTACAGGTGGCAACAATCTCCGGTAATATGTTCAACCAAATGGCTAA

ATGGGTTAAACAGGATAATGAGACTGGGATATATTACGAAACCTGGAATGTAAAGGCTAGCCCAGAAA

AGGGTGCAGAGACGTGGTTTGATAGCTACGACTGCAGCAAGTTCGTCCTGCGGACCTTCAACAAATTG

GCGGAGTTTGGAGCAGAGTTTAAAAACATAGAGACTAATTACACACGCATTTTTCTTTATAGCGGCGA

GCCCACTTACCTCGGTAACGAGACATCAGTCTTCGGGCCCACCGGAAACAAGACCCTTGGTTTGGCGA

TTAAAAGATTTTATTATCCATTCAAACCTCATTTGCCAACTAAGGAATTTCTCCTCTCTCTCCTGCAG

ATATTCGATGCGGTCATTGTTCACAAGCAATTCTACTTGTTCTACAACTTCGAATATTGGTTCCTTCC

AATGAAATTCCCATTCATTAAAATCACATATGAGGAGATTCCCTTGCCCATAAGGAACAAGACTCTCT

CAGGGCTCGATTACAAAGATGATGACGACAAATA
custom-character

The AGA protein sequence is:

(SEQ ID NO: 34)

MARKSNLPVLLVPFLLCQALVRCSSPLPLVVNTWPFKNATEAAWRALA

SGGSALDAVESGCAMCEREQCDGSVGFGGSPDELGETTLDAMIMDGTT

MDVGAVGDLRRIKNAIGVARKVLEHTTHTLLVGESATTFAQSMGFINE

DLSTTASQALHSDWLARNCQPNYWRNVIPDPSKYCGPYKPPGILKQDI

PIHKETEDDRGHDTIGMVVIHKTGHIAAGTSTNGIKFKIHGRVGDSPI

PGAGAYADDTAGAAAATGNGDILMRFLPSYQAVEYMRRGEDPTIACQK

VISRIQKHFPEFFGAVICANVTGSYGAACNKLSTFTQFSFMVYNSEKN

QPTEEKVDCIDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for AGA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

AGA-DNA

(SEQ ID NO: 35)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG6

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TGTCTCTACTTAAAATACAAAAATTAGCCG

GGCATGGTAGTAGGCAGTAGCAATCCCAGCTACTCAGGAGGCTGGGGCAAGAGAATCGCTTGAATGCA

GGAGGTGGAGGTTGCAGTGAGCTGAGATTACACCAGTGAACTCCAGCCTGGGCGATAGAGCAAGACTC

CATCTCAAAAAATAAATACATACATACATACATACATACAAATATCCATGGAAAAGTTGATATATTGA

GACCTTCTATCAGCCATTCCCACTATAGTGTAATTTAGCTGTTTCTCTGACAGGAATTTTTATTTAAG

AAGAAAGAATTTGGAGAAATAGACATAGTAGGAGGTAACAGATCAGGCTCTTTCCACCAGAAGAAACA

CAAATACCTTAAAAAACAGGAAGAGGCTAGAGAGATCAGTGGGGTACTAAGACCAATTTTCCATGTAT

TGTATTTTACAATTTTTGCTAAAGGCATGTCCTAATTCCTTAAGGCTGCATAAAAATACTCAGCCCAG

GAGCTAAGGAAAATTTACTCAGAGGACAATGTATGTTTTTCTGGCTTTCTTACCCTGTTTCACCCAAG

TTTCCAGTTTCACCTGCCATTGGGTTATGATTACTCCAGCACAGATGACTTGTTCCTCTTCCAAACCC

CATGAAAGGAACTTAGAAAATTTGTCTTTATTATATCTTTTAATTAACACTTCCCCAACGGGATAATG

ATACTTCTGGGCTATCTTATGTTCTTTAAATTATGTATTTAATTTCCTAGCAATCAATAAGAGCCTTG

AAGGTTTTGTAAGTCTCACAACTCCTACCTAGTTTATATTTTTACATTTATTTATTTATTTATTTTTG

AGACAGAATCTCACTCTGTTGTCCAGGCTGGAGTGAAGTGGTGCGATCTCGGCTCACCACAATCTCCA

CCTCCCGGCTTCAAGCAATTCTGCCTCAGCCTCCCAAGTAGTTGGGACTACAGGCATGCACCACCACG

CCCGGCTAATTTTTGTATTTTTAGTAGAGACGGGTTTCACTATGTTGGCCAGGCTGGTCTCGAACTCC

TGACCTCGTGATCCACCCACCTCAGCATCCCAAAGTGTTGGGATTACAGGCGTGAGCCATCGTGCCCA

GCCTAGTTCATATTTTTAAAGTTTGTATAGATTTATAGATGCTTTTAAAAATTATGTGATTATGTGTC

TTGCCTTGGCAACCTGGGCAGGCATTCCAGACACCCAAAGGGATTATTAGTTCATGTTCGCACGTCTG

CCCAGCAACAAAACTGAGCAGCCTCCACCAAGCACGTAAAATCCCCATTCCTCCTCTTATTCATTTAT

TTAGCACTTAATAGTGCCAGGCAGGAAGGTAAAAATACATTTAAAAAGGAATGGAGGTAGCCGTCTTG

CCCTGGAGGTGCAGGAAGCTGCACTTCAGTGTGCTAGGTAGAGGGTACATAGGCCGTTTCTGTTTTTC

TTCCAGCTCAGGGATTTATAATGAGAGGAAGTGCTACAAAAAGCTGTGGTGCGAAAATGACGGACGCT

ATGAATGGAAAAAAAATCTAAAATCAATCCGGTCCTAAGCAAACACGCTTCACCTACACTCATAACTA

TTGCAGACCTCCGAGGCCTGGGATCCCCAAGAATATACTGAGTTTGACAAACTTTTCAACTTCAACTT

TAAATTAAAAAGACAGTAAAAGAACCAAATCCATAGTACACAGCAATCGGCTAAAGTTCCTGGGGCCC

TGCAACCCAGAGTTGAATAATTTTGTATTAAATTCCCAATATCAAGCTAAATCTATTTTAACCACAGG

AAAAGCAGCAACTTGTCTGGCTATTTTAAAAATCTGAACAGCACTTAGGAAGAAGCACCTTAGCGCAG

GGAACAGCTCAGTGCCCCGTGACACAACTCTCCCGCGGGCCCAGGGACGCCTCGTCTCGCGAGAGTTG

AGGGACGCCTGAGCGAACCCCCGAGAGAGCGGGCGTGGGCGCCAGGCGGGCGGGGCACTGGGGAT
custom-character

ATGGCCCGCAAAAGTAACCTTCCCGTTCTCCTGGTACCG

TTCTTGTTGTGTCAAGCACTTGTACGCTGCTCTTCACCGCTCCCGCTTGTCGTTAACACCTGGCCTTT

CAAGAATGCAACAGAGGCGGCATGGCGAGCACTCGCATCTGGCGGGTCTGCCCTCGATGCAGTAGAGT

CCGGCTGTGCCATGTGCGAAAGGGAACAGTGTGACGGGAGTGTGGGATTTGGCGGCTCTCCAGATGAG

TTGGGAGAAACGACCCTTGATGCGATGATTATGGATGGAACAACCATGGATGTGGGGGCGGTCGGTGA

CCTCCGCAGGATAAAAAATGCTATTGGGGTGGCGAGGAAAGTCCTGGAACACACCACCCATACTTTGC

TCGTTGGTGAGTCTGCAACAACGTTCGCGCAAAGCATGGGCTTTATAAATGAGGACCTGTCCACAACT

GCCTCTCAGGCTTTGCACTCTGACTGGTTGGCGAGGAATTGCCAACCCAATTACTGGAGAAATGTTAT

TCCCGATCCATCCAAGTATTGCGGGCCTTATAAGCCACCGGGAATCCTTAAACAAGATATACCTATTC

ATAAGGAAACCGAGGATGACCGGGGACATGATACGATCGGAATGGTAGTGATCCACAAGACAGGGCAT

ATTGCGGCGGGGACCAGCACAAATGGTATCAAATTCAAAATTCACGGTCGAGTCGGTGACTCCCCCAT

ACCTGGTGCCGGGGCTTATGCTGACGACACAGCTGGAGCTGCTGCCGCGACAGGTAATGGTGATATCC

TGATGCGGTTTCTCCCATCATACCAGGCTGTCGAATATATGAGACGGGGTGAGGACCCCACTATAGCC

TGTCAAAAGGTTATTTCTCGGATACAGAAGCATTTTCCGGAGTTTTTCGGTGCAGTTATCTGCGCCAA

CGTTACTGGTAGCTATGGAGCTGCATGTAACAAGTTGAGTACGTTTACCCAATTTTCATTCATGGTTT

ATAACTCCGAGAAAAATCAGCCGACTGAGGAAAAGGTTGACTGTATTGACTACAAAGACGACGACGAT

AAATA
custom-character

The IDUA protein sequence is:

(SEQ ID NO: 36)

MRPLRPRAALLALLASLLAAPPVAPAEAPHLVHVDAARALWPLRRFWRST

GFCPPLPHSQADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTR

GSTGRGLSYNFTHLDGYLDLLRENQLLPGFELMGSASGHFTDFEDKQQVF

EWKDLVSSLARRYIGRYGLAHVSKWNFETWNEPDHHDFDNVSMTMQGFLN

YYDACSEGLRAASPALRLGGPGDSFHTPPRSPLSWGLLRHCHDGTNFFTG

EAGVRLDYISLHRKGARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEA

DPLVGWSLPQPWRADVTYAAMVVKVIAQHQNLLLANTTSAFPYALLSNDN

AFLSYHPHPFAQRTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQ

LWAEVSQAGTVLDSNHTVGVLASAHRPQGPADAWRAAVLIYASDDTRAHP

NRSVAVTLRLRGVPPGPGLVYVTRYLDNGLCSPDGEWRRLGRPVFPTAEQ

FRRMRAAEDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHVCARPEKPPGQ

VTRLRALPLTQGQLVLVWSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPS

TFNLFVFSPDTGAVSGSYRVRALDYWARPGPFSDPVPYLEVPVPRGPPSP

GNPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for IDUA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

IDUA-DNA

(SEQ ID NO: 37)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TCCAGGGAAGGTGTACTTTTCTGTCCACAG

GTGTCCCGGTGAGCGGCTCACCTTAATTCTCTCAGGGCTTGAGGTGATTTAAGGCTGGCTTCAGTCCC

CACAAAGACAATTCTGTTGCTGGTTTACCTTTGCTTTTAGGGGATAGAACTTTGGGGTCCCAAGAAAA

ACCCAAAGTCTTTACCAGGCCCCCCGCCTGAGCCTCGACTTCTGTCCTGTGGCCACAGTGTGAGGAAC

GAACGCAGCAGCGTGTCGCCATGTCTTGTGTGGCTGGGATACGCTGCAGGGGTGTGGAGTCGCCGCCC

CAAAGCGGGCCCCGCCCCCTCCCGGCTTGTCCCTGCAGAGCCCCGAGGCCTCAGAGGCTCCTCAGAGC

TCCCAGTGCCCTGGACGGTTCCGTTCAGCGCTCTCCAGTTCTGATGGTTGCTCTCAGGAGGCGGCTGG

TCTGAAACAATTCAGTTTCCATTGCTGTGTCCTGCACCACGGTGTGGGACTGGTGGTTTCTTACTGTT

TTTCTCAGTTCTCTGACGCTTTGAGGAATTGTTTTTAAAGCGAGTTATCCATCATTTTAGTTGTTTTC

TCTGGGGTCGTTGGACTGAGGGTCTTACCCCGCTGTTCCTGGAGACAGTTCTGTACTTGCATGGTTTC

TCTCGCCTTTCCCTCCCTTTCTTACTTTTTAGTTTCTTAATGAATTTTTTTGTATTATGTTTTTCCTC

CTTGCTAATTTGGAATATATACACACTATTTCACTTTTAAATGGCTAATCACTTTTAATGCAATTTCA

ACATAAGAAGACCTAATGTTAAGCAATATTTTAACCCCTCTCCCCAAAATAAAAAGACCCAGAACACT

GTAACTCTAATTATCCTTCTCCCAACTTAGAGAGGATTATTGTCCAGTATTTTCGTTTTGTTAGTAGA

CTGTTCTTTTTTTCTTTTCTTTTTTTAGAGATGGGGTCTCATTTTGTCAACCAGGCTGGAATGTAGTG

GTGTGATCATGGCCCGTCTCAGCCTTGAACTCCTAAGCTCAAGCAATCTCCCACCTCAATTTCGTGGG

TAGCTGGGCCTCACAGGCATATACCATCGCATCTGGCTAAATTTTTTTTTTGTACAGATGGGGTCTTG

GTACATCTCCCAGGCCGATTTCAAACTCCAGGCCTCAAGTGATCCTCCCGTGTTGGCCTGCAATTCCA

AAGTGCTGGGATTGCAGGTGTGAGCCACCGCACCAAGCCTGTTCTTTCCATTATTATTTTTATACAAT

GTTTGCTTGGATTCACACATGCATACATGGACTACACATGTACTACAGTTGTCCCATGGTATCCTCGG

GGTATTGGTTCCAGGACCCTCCCAGATACCAAAATTTGCAGGTGCTCAAGTACTTGATATAAAATGGC

ACAGTATTTGCACATTACCTACGCACATCCTACTGTGTAGTTTAAATCAAGATTACTTATAGTCCCTA

AAACAATGTAAATGCTCTGTAAATAGCTGTTATACTGTATTGTTTTAAAATATGTATTATTTCGTATT

GCTTTGGCTTTAAAACAATATTTTCAGTCTGCTTGGTTGAATCCATGGATCTGAAGCCAAGTGTAAGG

AGGGCCCAGTGTGCTCTTCTGGGGTAATTCTCCTTCCTGCTAAAGCGCACGCTTTACTCAGGAGGCTG

GGGTGAGAAAATCGCTGAAGCCCCGGAGATGGAGGTTGCAGTGAGCTGAGATCGCGCCACTGCACCTC

AGCCTGGGCGACAAAGCAAGACTCTGTCTCAAAAACACACAAAAACAGAGAAAAACAAGACAGTAATG

GCTCAACTCACATAGCACCAACGGGCGAAGCGTTCTTCTGAGCGCTTTCCGAGTCATCGGTCCTCAGA

GCAGCCCCTGAGGCCCGCAAGGAAGCGGGGCTCCAAGCCCTGCCGTGCTCCCGGCTCCCCGAGGCTCC

CCGAGGCCACCCAACCCCTCCCACCCGGCCATCGCCCCCTCACCAAGGCCCCGCCCCGCGGCGGCGGT

CACATGGGGTGCGCGCCCAGACTCCGACCCGGAGGCGGAACCGG
custom-character

ATGAGGCCACTGAGGCCAAGAGCTGCACTTCTGGCGCTCTTGGCGAGTCTTCTCGCCGCA

CCTCCCGTTGCCCCTGCGGAGGCACCACATCTCGTTCATGTTGACGCTGCGAGGGCTTTGTGGCCACT

TAGGCGATTCTGGAGAAGTACGGGCTTCTGTCCACCGCTGCCGCACTCACAGGCAGACCAATATGTCT

TGAGCTGGGATCAGCAACTCAACTTGGCGTATGTGGGAGCTGTCCCGCATCGCGGTATTAAGCAAGTG

CGAACGCATTGGTTGCTTGAGTTGGTAACCACGAGAGGTTCCACTGGGCGAGGGCTCTCCTATAACTT

CACACACCTCGATGGGTATCTGGACCTGCTGCGAGAAAATCAACTCCTTCCCGGGTTCGAACTGATGG

GCTCCGCATCTGGCCACTTCACGGACTTCGAAGATAAGCAGCAGGTCTTCGAATGGAAAGATCTGGTG

TCAAGTCTGGCTCGCAGGTATATTGGACGATACGGTCTGGCCCACGTCAGTAAGTGGAATTTTGAAAC

GTGGAACGAACCAGACCACCATGACTTTGATAACGTATCTATGACTATGCAGGGATTTCTCAATTACT

ATGACGCTTGCTCTGAAGGACTCCGGGCTGCAAGTCCAGCTCTCCGCTTGGGCGGGCCTGGGGATAGT

TTCCATACACCTCCCCGATCCCCGTTGAGTTGGGGGCTCCTCCGACATTGTCACGACGGGACGAACTT

TTTCACCGGTGAAGCGGGAGTTCGGCTCGATTACATCTCTCTGCATCGGAAGGGCGCAAGAAGCTCCA

TAAGTATCTTGGAGCAAGAGAAAGTCGTGGCGCAGCAGATCAGACAGCTCTTCCCGAAGTTTGCGGAT

ACACCTATATACAATGATGAGGCTGACCCACTGGTCGGCTGGAGCCTGCCCCAGCCGTGGAGGGCTGA

CGTAACATACGCCGCGATGGTGGTTAAGGTAATAGCCCAGCACCAGAATCTTCTGTTGGCAAATACCA

CGAGTGCATTCCCTTATGCTCTGTTGTCAAATGATAATGCCTTCTTGTCTTACCACCCGCATCCTTTC

GCTCAACGCACGCTGACCGCCCGCTTTCAAGTAAATAACACTCGCCCACCCCACGTGCAGCTCCTGAG

GAAGCCCGTTCTGACTGCTATGGGGCTCCTCGCGCTGCTGGATGAGGAGCAGTTGTGGGCTGAGGTAT

CTCAAGCCGGGACTGTATTGGACTCCAATCACACTGTGGGGGTTCTTGCTAGCGCGCACCGCCCTCAA

GGACCTGCCGACGCCTGGCGCGCTGCAGTGTTGATATATGCCAGTGATGATACGCGAGCCCACCCGAA

TAGGTCTGTTGCCGTGACGTTGCGCCTCAGAGGCGTTCCCCCTGGTCCAGGACTCGTCTATGTTACTC

GATATTTGGATAACGGCCTCTGTTCCCCTGACGGTGAATGGCGGAGATTGGGGAGACCTGTGTTTCCG

ACAGCGGAGCAGTTCCGGCGCATGCGAGCGGCAGAAGACCCTGTTGCAGCTGCTCCACGACCGCTCCC

TGCAGGCGGCAGGCTTACTTTGAGACCAGCTTTGAGGTTGCCGAGCCTCCTGTTGGTCCATGTATGCG

CGCGGCCAGAGAAGCCACCCGGGCAAGTAACCCGGCTTCGCGCCCTCCCGCTCACCCAAGGCCAGCTC

GTGCTTGTATGGAGCGACGAGCATGTTGGATCTAAGTGTTTGTGGACTTACGAGATACAATTTAGCCA

GGATGGAAAGGCGTATACCCCTGTGAGTCGGAAGCCTTCTACATTCAACCTCTTCGTGTTCAGCCCCG

ACACAGGTGCTGTTAGCGGGTCCTATCGGGTGCGGGCGCTGGATTACTGGGCACGGCCCGGGCCGTTT

TCCGACCCTGTTCCCTACCTGGAAGTTCCCGTTCCGCGAGGCCCACCTAGCCCTGGGAATCCAGACTA

TAAGGACGACGACGATAAATA
custom-character

The GDNF protein sequence is:

(SEQ ID NO: 38)

MKLWDVVAVCLVLLHTASAFPLPAGKRPPEAPAEDRSLGRRRAPFALS

SDSNMPEDYPDQFDDVMDFIQATIKRLKRSPDKQMAVLPRRERNRQAA

AANPENSRGKGRRGQRGKNRGCVLTAIHLNVTDLGLGYETKEELIFRY

CSGSCDAAETTYDKILKNLSRNRRLVSDKVGQACCRPIAFDDDLSFLD

DNLVYHILRKHSAKRCGCIDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GDNF and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GDNF-DNA

(SEQ ID NO: 39)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AAACCCTCTTAAGACGGAAGGGAAATCTAG

TGCCTCTGTGGCTTCCTGCTGGCGGGCACCGCGATTTGGAATGGCGCATTAACCCCGCGCCTCCATGC

TCCTCCGGTCGGACCGCCAGCCATTTCGCACGCACCCGGGAGCTGGCACCGGCGGGGGGCTTGAGGGG

GGAAGCTCGCGTTCCCCAGGTCCTAGCTGCCAAAGTACCTTTCTGGGCTCATTTTGCATGGCCTGGTG

CAGTTTTCCTGTGTCTGCACATCGCGACCCAGAACCTAGCTTTTTCCCGAGTTTGCAAACCAGCCCGC

GAGGCAAGAGGCGCTCGGTGCTGCAGGTCACTAGGAGTTTCTAGTCCCTACACCCTCTCGAGCCCAAC

AGCTGCATAGCGAACAAACAGACGCTCAGGAGATGTAAAATGCATTAGTCTCTGCAGAGGTGGGAGGT

GGCGGCCGAATTAAAGGCTTCCCCGGGTTGCCTGCACCGGGACAGGGAGTGGGGTTCCGGGTAGAGAT

GAGGACTGGAACCCTGGAATGGAGGCGGGGGTGCCTGTGAACTAATGGCTAGGAAAGGCACTGAGGTT

TTTGCATTAACCTGGGTTTTGCATTTCCCTCCCGCATGGGAAAAAAAAAATCGAGTTTTTCCTAAGAA

CCGTTTTATGGAGCCGGTCGAGGGGATAGGATAATCGACTGCACGAATCTCGCAGATTCCGCTTGAGG

AGATTCTCTCTAGGTCACTAGTGCCCTGGAGACGAACCCTGGGATTAGGAAGGCACTGGATAACACTG

CACCCCAAGATGCCTCGGTTCTTCCCCGTCTCCTCATTGGTTGGAACTCGCCCCCAAATTTACAGCCC

CTTTTTCTAACCCACCCCCAGCTGCGTGGCCCTCCTTTGTAGGGGTGTGAGGATTGAGAAGCCAAACA

GAGCCCACCTCGGGCTGAAAAGAGCTGAACCCCCTACTCTGCGCCGTACCACGGTCTAGGCCTTCCAG

TGCCAGAGCACC custom-character

ATGAAGCTCTGGGATGTCGTGGCG

GTGTGTCTTGTCCTTCTCCATACTGCGAGTGCGTTTCCACTGCCAGCTGGGAAAAGACCCCCAGAGGC

CCCTGCAGAAGACCGATCTCTTGGGAGGAGGAGAGCACCGTTCGCTCTGAGCAGCGACAGTAATATGC

CGGAGGATTATCCCGATCAGTTCGACGACGTAATGGATTTTATCCAGGCAACGATAAAGCGGCTGAAA

CGGAGTCCGGACAAACAAATGGCAGTGCTCCCGCGCCGGGAACGAAATAGACAGGCCGCCGCGGCAAA

TCCGGAAAATAGTAGGGGCAAAGGAAGACGGGGGCAGAGAGGCAAAAACAGGGGCTGTGTATTGACTG

CCATTCATTTGAACGTAACGGACCTGGGGCTTGGTTACGAGACTAAAGAAGAACTGATATTTAGATAC

TGCAGTGGATCTTGCGATGCCGCTGAAACCACCTATGACAAGATTTTGAAGAATCTTTCTCGAAACAG

AAGACTGGTTTCTGATAAGGTTGGTCAGGCGTGTTGCCGACCCATCGCGTTTGACGACGACCTTAGTT

TTCTCGACGATAATCTTGTCTATCATATCCTTCGCAAGCACTCCGCTAAGAGGTGCGGATGCATTGAT

TACAAAGATGATGATGACAAGTA
custom-character

The GLB 1 protein sequence is:

(SEQ ID NO: 40)

MPGFLVRILPLLLVLLLLGPTRGLRNATQRMFEIDYSRDSFLKDGQPFR

YISGSIHYSRVPREYWKDRLLKMKMAGLNAIQTYVPWNFHEPWPGQYQF

SEDHDVEYFLRLAHELGLLVILRPGPYICAEWEMGGLPAWLLEKESILL

RSSDPDYLAAVDKWLGVLLPKMKPLLYQNGGPVITVQVENEYGSYFACD

FDYLRFLQKRFRHHLGDDVVLFTTDGAHKTFLKCGALQGLYTTVDFGTG

SNITDAFLSQRKCEPKGPLINSEFYTGWLDHWGQPHSTIKTEAVASSLY

DILARGASVNLYMFIGGTNFAYWNGANSPYAAQPTSYDYDAPLSEAGDL

TEKYFALRNIIQKFEKVPEGPIPPSTPKFAYGKVTLEKLKTVGAALDIL

CPSGPIKSLYPLTFIQVKQHYGFVLYRTTLPQDCSNPAPLSSPLNGVHD

RAYVAVDGIPQGVLERNNVITLNITGKAGATLDLLVENMGRVNYGAYIN

DFKGLVSNLTLSSNILTDWTIFPLDTEDAVCSHLGGWGHRDSGHHDEAW

AHNSSNYTLPAFYMGNFSIPSGIPDLPQDTFIQFPGWTKGQVWINGFNL

GRYWPARGPQLTLFVPQHILMTSAPNTITVLELEWAPCSSDDPELCAVT

FVDRPVIGSSVTYDHPSKPVEKRLMPPPPQKNKDSWLDHVDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GLB1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GLB1-DNA

(SEQ ID NO: 41)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AATCAATACACTAATACAAAACTATTATTT

AATATTTAGACCGTGTACCATTATCAAAATCAGAAAGTTAACATTGATGCGGCCGGGCACAGTGGCTC

ATGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCAAATCACTTGAGGTCAAGAGCTCCAGACC

AGCCTGGCTAACATGGTGATACCCCATCTCTACTAAAAATACAAAAATTAGCCAAGCCTAGTGGTGGG

TGCCTGTAATCCCAGCTACTTTGGAGGCTGAGGTGGGAGAATCACTTGAACCTGGGAGGCGGAGGTTG

CAGTGAGCCGAGATTGTGCCACTGCACTCCAGCCTGGGTGACAGAGTGAGACTCTGTCCCCCCACCCC

CCCAAAAAGGAAATTAACATTGATGCATGGTACTAATCTAACCTACAAGTCTAATTCTGATTTCATCA

ACTGTCCCACTAACATCCTGTATATACCAAGCTTCTTATCGTCATCATCTCTGGTAATTTCCCCAATT

ATCCAGTGAATTTGATATTATTAGCCCTGCTTTACCAACAAAGAAACTAAGCTCAGAGAGGTTAAGTA

ATTTGCCCACAGTTACACAGACAGTAAGTGGCAGAGCTGGAATTCCAACTCAAGTGTACTTCCTCCAG

AGCCCTTGTTCTTTAATACTGAACTAGAATTGCAGAGCTTGGAAAGGACTTCACAGTGCAAGGACACG

GAATTGGTACTACAGGCATGAAAAGAAGCCAGGCACGGTGGCTCATGTCTGTAATTCCAGCATTTTGG

GAGTTCCAGGCAGGTAGATTGCTTGATCCCAGAACTTCAAGACCTGCCTGGGAAACGTGGTGAGACCC

TGTCTCTACAAAAAATACAAAAATTAGCCGGGTGTGGTGGCGCACGCCTGTAGTCCCAGCCACTTGGT

AGGCTGAGACGGGAGAATTGCTTGAGCCCAGGAGGCCAAAGCTGCAGTAAGCCGTGATTGCGCCCCAC

TCCAGCCTGGGTGACAGAGTGAGACCCTGTCTCAAAAAACACAAAAACAAAACAAAAAAACAACCCCC

CAAACCAAAAAACAAAAACCTAAGAAAAGCCAGTAACTGATACTTTCTCAATCTCTCAATGAAATGTC

CTTTCTGATACTTTCTCAATCTCTCAAGGACATGTCCGGTAGGAAAGGAGAAAGGAGTGAACAAATAG

AATTTTGGCTACTTTGTTATACAATGTAAAAAGGCTTTTTGGAACACCAAGGCATAAACTAAGGTTAT

TTTAAAAAAGAAAATTTTTTTTTGATACGGAATTTCGCTCTTATTGCCCAGGCTGGAGCGCAATGGCT

CGATCTCGGTTTACTGCAACCTCCACCTCCCGGGTTCAAGCGATTCTCCTGTCTCAGCCTCCTCAGTA

GCTGGGATTACAGGCGCCTGCCACCACGCCCGGCTAATTTTTGTATTTTTAGTAGAGACGGGGTTTCA

TCATACTGGTCAGGCTGGTCTGGAACTCCTGACCTCAGGCGATCCGCCCGCCTCGGCCTCCCAAAGTG

CTGGGATTACAGGCGTGAGCAGGATTTTCATTCTAACAAGTTCCAGGTGAGTTGATACAGTGGCTCCA

GGGACCGACCACATTTTGCTAACCCCCGGCTTAGAGTTATTCAAAGAGCCCGTATATGAGACGCGGAT

TCCATCTAGGGCGTTTAGGTTTAATGATTAACAATTTCCCTCTTCTGCTCTCTCAAGGCAGCCAGGGA

ACAGGGAGACCATGATTCATGTCCAATCCCCGAGGCGCGTTATCAAGCTGCTGAAAGCAGGCCCTCCG

GACTGCAGTTCCAAAGGGTCCCTTCCCAGGGAAGACGCCTGCAAAACCCAGATAGTACTATCCTGGAG

TCACGCGGCGGCGCGCAGCCTCCTAGCCGCCCCCACCCGCCCGGCTCGG custom-character

ATGCCGGGGTTCCTGGTGAGAATACTTCCCCTGTTGCTTGTGTTGCTCCTGCTTG

GTCCCACCAGGGGTTTGAGAAACGCGACACAAAGGATGTTTGAGATTGATTATAGTAGGGACTCATTC

CTCAAAGACGGGCAACCATTCCGCTACATCTCAGGCTCCATTCATTACAGCCGAGTACCTCGCTTCTA

TTGGAAGGATCGGCTGTTGAAGATGAAAATGGCCGGGCTCAACGCGATCCAAACTTATGTCCCCTGGA

ATTTTCATGAACCGTGGCCTGGCCAGTACCAGTTCTCCGAGGACCACGATGTGGAATACTTTTTGAGA

CTTGCTCATGAGCTTGGCTTGCTTGTAATTTTGCGGCCGGGGCCTTATATATGTGCAGAGTGGGAGAT

GGGCGGACTTCCAGCGTGGCTTCTTGAAAAAGAATCAATTCTGCTCCGGAGCTCAGACCCTGATTATC

TTGCCGCTGTTGACAAATGGCTGGGGGTCTTGCTCCCTAAAATGAAACCACTCCTTTACCAGAACGGA

GGTCCGGTAATTACCGTTCAGGTTGAAAACGAATACGGTTCCTACTTCGCCTGCGACTTCGACTACCT

CCGCTTTTTGCAAAAGCGATTTCGGCACCACCTTGGAGATGACGTCGTCTTGTTTACGACTGACGGGG

CTCACAAGACATTTTTGAAGTGTGGCGCCTTGCAAGGTTTGTATACCACCGTTGACTTTGGCACCGGT

AGTAATATCACTGATGCATTTCTCTCTCAGAGAAAGTGTGAGCCAAAGGGTCCTTTGATCAATTCAGA

GTTCTATACTGGATGGCTGGACCACTGGGGACAGCCTCATAGTACGATCAAGACTGAAGCCGTCGCGT

CTAGCCTTTACGATATCCTCGCACGCGGAGCCTCCGTTAATCTGTACATGTTCATCGGTGGGACGAAC

TTTGCGTACTGGAACGGAGCAAATTCTCCGTATGCTGCACAACCCACTAGCTATGATTATGATGCTCC

TCTGAGTGAGGCGGGCGACCTTACAGAGAAATATTTCGCTCTCAGGAACATCATCCAGAAATTCGAGA

AAGTTCCAGAGGGGCCCATCCCACCTTCAACACCAAAGTTCGCCTATGGGAAAGTCACACTGGAAAAA

TTGAAAACAGTAGGAGCAGCTCTCGATATACTGTGCCCTTCCGGTCCGATAAAGTCTCTGTACCCACT

TACATTCATTCAAGTTAAACAGCATTATGGTTTTGTGTTGTACAGGACTACCCTTCCCCAAGATTGTT

CAAATCCTGCACCGTTGAGCTCACCACTTAATGGGGTGCATGATAGAGCGTATGTCGCGGTGGACGGT

ATCCCCCAAGGGGTTTTGGAGCGAAATAACGTCATTACGCTCAATATAACTGGTAAGGCTGGGGCCAC

CCTGGATTTGCTTGTAGAGAACATGGGGCGGGTTAACTATGGCGCGTACATCAACGATTTCAAGGGTC

TGGTGTCAAACCTTACGCTGAGCAGTAACATACTGACTGATTGGACTATCTTTCCTCTTGATACGGAG

GACGCTGTTTGTTCTCACCTTGGGGGCTGGGGACATCGCGACTCAGGGCATCATGATGAAGCTTGGGC

ACATAACTCCTCTAACTACACGCTCCCCGCCTTTTACATGGGCAACTTCAGTATACCAAGTGGCATCC

CCGACCTCCCTCAAGATACCTTTATTCAATTCCCAGGCTGGACAAAGGGTCAGGTCTGGATCAATGGT

TTTAATTTGGGAAGATATTGGCCAGCCCGGGGACCCCAGCTGACTTTGTTTGTGCCCCAACATATTCT

GATGACGAGCGCTCCCAACACTATAACCGTTCTCGAATTGGAGTGGGCCCCCTGTTCCAGTGACGATC

CTGAGCTCTGCGCAGTCACCTTTGTAGACAGGCCAGTCATTGGTTCCTCTGTGACTTATGACCATCCA

TCCAAGCCTGTCGAGAAGAGATTGATGCCGCCTCCTCCGCAGAAGAATAAGGATAGCTGGCTCGACCA

TGTAGACTACAAAGACGACGACGATAAGTA
custom-character

The PMP22/MFN2 protein sequence is:

(SEQ ID NO: 42)

MLLLLLSIIVLHVAVLVLLFVSTIVSQWIVGNGHATDLWQNCSTSSSGN

VHHCFSSSPNEWLQSVQATMILSIIFSILSLFLFFCQLFTLTKGGRFYI

TGIFQILAGLCVMSAAAIYTVRHPEWHLNSDYSYGFAYILAWVAFPLAL

LSGVIYVILRKREDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PMP22/MFN2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

PMP22-DNA

(SEQ ID NO: 43)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GGAGTTTTCCTCACCTGACTCTGGGAAGGG

AAGAGAGTCTGGCCCAGATGGGTAAAGACAAGTGTGTTGGCATCTGGTAGACAGGGCCAGTGGCACAC

AACAGTGAACAGCTCTACTGCTGACAGCCAACAGGGACTTCGGGGTTTGGCTGCTGGAGATGGAGGAC

CTGGGCAAAAGAGACGTGAGGCCAAGAGAGCAGGTCTCAGAATGTGGAGCTCATGGAAGGAGAGAGGG

AGGGCTAATCAGACTGCTCCTATCTGGCCAGAAGCCATGCCCCACACTCACCAGGCCCTACCCCTTTT

CCTCTGAATCTTTAGCTCTTAGATCAGAAATAATCTTACGTGTCTTCAGGCTTGATCCTGGCCTGACG

GACAGCAGCCTCTGTCGTGTAGCCTTTGGAGCTGATCATGGCAGTACCCAGGAAAAGACTGTCTGGAG

AGGCTGCAAAAACCATGCTCACTGTTCCCAGTCCCCGTACAGACCATGTCAGAGGAGGACTGAGGGAG

GCTCCTCTCTCTCTCTCTCTGTCACACACACGCACACGCGCACACACACACACACAGATACACGCGCA

CACACACACACCGTTTTGCCTGGCAGAACAGACTTATAACTTGCATAATACTGCAGCAGCCCACACTG

TACCTCATCTCCATTTGGGTTCCACAACAGAAGGGAGCTGGAAGGAAATCAGCGACAATCTAACTCCA

CATGACAACCTGGCTGGACAACGAAACATCCAGCGGGGAGAAAGACACTGGAAATTACCCATACCTGA

GCCCCATCCCAAAACACCTGAGTCAGCTTCTCTGACCATGGCCCAGGCTAGGTCATTTGCAAAGCTCT

TGAGTGATTCTAAAGAACCACTGCTGTGAAAAATAAAAATGATTTCAGCAAAGAGAGAAAGGTGAAAC

TATTTTATTGGCACTGGCTGTGATGCTGGCTGTGAGCAGATGCTGGCTGTGGGCAGAACAGGGGAGAG

GGCCATTGAGAGGCCCTTGTGACTGGAGAGTCCAATCAAACGTAAAGTGTGTGACAGGGAGGGACTCC

TCCAAATTCTGCAGGTCTCTCCAGACTGGGGATCCCTAACACAAGAGGAAGTCTTATGCCCCAAGTGC

CAGAATTCCAGGAAACTCATGCAATGAAACCAGTCCTCTTGTGTCAGAGTTTGCAGCTAGAAGCGGTT

CAAGGGATGGAGGACTCTCTGGGAGCTGGAGTGGTACGCTGCAAAGAACCTAAATATGCCATAACTTC

CTTTACTTCCCTCTCCAAGAATTTCCAATTGCTCTTCCAGCCTATTCTGCCTGACAGGTTAGAAAGTT

TTCAATAGTTTTCAATAGAGGTTCGTTTACTTGCATTGAATTATCTCATGAAGGTCAGCTTGATTCGG

GCACATTAAAGACAGAGTCGGAAGAACACATTTCCCTAAGTTTTATTCTAATGTACAACACATGTGAT

CATTTGCGATGGGGTCTAGGCAGACAAGGCAGGTAACAGGGAGTCCTTCCAACCAGGGGTTGGAACAA

AGGAGGCTTGATTTGGTGACTCTTGAGACATTTGGCTCACTGCTGTGATGCTGTGAGAGATTAGCTGT

GCAATGTTTGGGCTCCTTAAAAGGAAGTTTATTTAAAATAAAACTTACCTGCACGTATGTAACACTGT

AGACACAGATCCTTCCCACAGTATATTTAATCTCTGCAGAATTCACTGGGAGGGGAGGGGAGCCAGTG

GGACCTCTTGGCTATTACACAGGTTGGCACTTCCAGAGAGAACAGTCTTGGCATCACAGGCTTCAGGC

ATACTCAAAGCTCTTCTCCCTTCTGATTCCAGTTTCTCCATGCCCTGCAGGGCCTCTTGGGATTATTG

TATTCTGGAAAGCAAACAAAGTTGGACACTGTCTCTTTAAATAATAGAGGCTGAGAACCTCTCAGGCC

ACCATGACATATCCCAGCATTGGACCAGCCCCTGAATAAACTGGAAAGACGCCTGGTCTGGCTT
custom-character

ATGCTTTTGCTGCTTCTCTCCATAATAGTGTTGCACGTAGC

AGTCTTGGTCCTGCTCTTTGTTTCTACCATTGTATCACAGTGGATTGTGGGTAACGGCCACGCTACCG

ATCTGTGGCAAAATTGTAGCACGTCCAGCTCTGGTAATGTACACCATTGTTTCAGCAGTTCACCTAAC

GAGTGGCTCCAGTCAGTCCAAGCCACAATGATCCTGAGCATAATTTTTAGCATCCTCAGCCTTTTCCT

GTTCTTCTGCCAGCTCTTTACATTGACAAAGGGTGGACGGTTCTACATTACAGGGATATTCCAAATTC

TTGCGGGTCTGTGCGTGATGTCCGCCGCCGCCATCTACACCGTTAGGCACCCTGAATGGCATCTTAAC

TCCGACTATAGTTATGGTTTCGCCTATATCCTCGCATGGGTGGCTTTCCCTCTTGCCCTGCTTAGCGG

CGTAATCTATGTGATTCTCAGGAAGAGAGAAGATTATAAGGATGACGATGACAAATA
custom-character

The MECP2 protein sequence is:

(SEQ ID NO: 44)

MAAAAAAAPSGGGGGGEEERLEEKSEDQDLQGLKDKPLKFKKVKKDKKE

EKEGKHEPVQPSAHHSAEPAEAGKAETSEGSGSAPAVPEASASPKQRRS

IIRDRGPMYDDPTLPEGWTRKLKQRKSGRSAGKYDVYLINPQGKAFRSK

VELIAYFEKVGDTSLDPNDFDFTVTGRGSPSRREQKPPKKPKSPKAPGT

GRGRGRPKGSGTTRPKAATSEGVQVKRVLEKSPGKLLVKMPFQTSPGGK

AEGGGATTSTQVMVIKRPGRKRKAEADPQAIPKKRGRKPGSVVAAAAAE

AKKKAVKESSIRSVQETVLPIKKRKTRETVSIEVKEVVKPLLVSTLGEK

SGKGLKTCKSPGRKSKESSPKGRSSSASSPPKKEHHHHHHHSESPKAPV

PLLPPLPPPPPEPESSEDPTSPPEPQDLSSSVCKEEKMPRGGSLESDGC

PKEPAKTQPAVATAATAAEKYKHRGEGERKDIVSSSMPRPNREEPVDSR

TPVTERVSDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MECP2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

MECP2-DNA

(SEQ ID NO: 45)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TCCTTGTTTCTTCCCTTGCTCTATGCCCTA

CATCCAATCCTTTTGTTCAGTTCTGAAAACATATCTTGAATCTCACAACTTCTCAGAGCTGCACTGCT

GCCACCCTAGTTAAAGCTACCATCAACTCTTTCTCCTAGACTGTTCCAGGGCCTTGCAACTAGCCTTG

TGCTGTAGTTTTGTTTCATCACGTCCAGTTCTCCACTCTACACCTGCAACATAGATCAGACAGCTCCT

GGCTCAAAATCCTCTGAGGGCTTCTCATCTTAGAATAAACTCTCGGTTCTGGCCGGGTGCGGTGGCTT

ACGCCTGTAGTCCCAGCACTTTGGGAGTCCGAGGCGGGCGGATCACTTGAACTCAGGAGTTTGAGACC

AGCCTGGGCAACATGGTGAACTCCCATCTCTATCAAAAATACAAAAACTTAGCCAGGCGTGGTGGTTC

GCATCTGTGGTCCCAGCTACTTAGGACGCTGAGGAGGGAGGATCGCTTGAGCTCAGGGTGGACGTTGC

AGTGAGCCAAGATTGCGCCACTGCACTGCAGCCTGGGTGACAGAATGAGACCCCATCCCCACCCCCCC

CAAAAAAGAATGAACTCCCAGTTCTCATAGTGGCCCCAGCTGCCTTTCCAATCACATTCCCTACCACT

CTCCAGCAACACTGACTTCCTCGTTAGTCCCCAACATGCCAGGCATAGTCTCTCCTCATGTCCTTTGA

ACTTGCCTGGAATGTTCTTTCCCCAGATATTCATATGAGGGAGTAAAATGAGGGTGAAAACCAGCAGA

TATCTAAATAGCACCCCCTTCACTTAGTTTATCTTTCTCAAAGCCCTTATCACTATGTGAAATGATAT

ATTATACTTATTTGTATGCTAGTATGAATCTTCCCGGCAAGAATGTTAGTTTGCTGTCTGTTCAGTAC

CGTGCATCCAGAGCCTGGAAGAGTGCCTGGCACATAGCAGGTAGTCAATAAATGAATGGGGGCAAGCA

GCCAAATCAGAATCAGGTTTTCTTGCTAAGCATAGAACTAACAGAAGGATCATTGAATGGATTGGATA

ATGACTGGCATCAGGGTAAGGTCCCCTTAACAAACACTCCTGTCCTGAACACCTGGTTAGCTAACAGT

TTTCTCATACTCTTATTTTCCCAAAACACAATTGCTGGATCTCAGCTCCAAATCAACTCTTCTAGGAA

AGTGAAAAATTGCTGGATCTCAGCTCCCAAATCATATCTTCCAGGCAGAGCTAACATTGCCCCTTATT

CACACCTCCACCAAACCATCTGATCCAACAGTGACAGGTGTCACGAGGCCTTGGCATGCACTCTCTTC

CCCCGCCAGAGTTCTGCGAAAGCCAGGGTTGCGATTTGTTGTCAGTTTATTCCCCGCCTCTATGAGAG

TGTGAGCACTGGGCAGGCTCGGATGAAATAATGCATTGAGTAGGCCTCTGAAACCAAGGCCCCTCAGC

TGGGGCAACGTCAGGCTCCAGGGTGGGCAACTTTGCTGCTTCTGCCGAAGATAGTGATATTGAGAAAA

TGTGGGTGCAATGAAACGCTTATTGCAGCGCACTCGGTGCATCTGTGGACAGAGGGTCAATCGCCCCT

CAGAGCAGCGCAAACAGGCGTCCCAAGCCTAGGCCTTCACTTGCCCCAGCATCCGCAAGGGTCCATTA

ATCCTTAACATTCAAATTCCGCCCACTAAACCAGTCCCTCCGCGCCCAAGCCGCCTCTTTTCCCCAAA

CGACGGCCGAAAGCAGCCAATCAACAGCTGGAGGGGTCCGCCCCCTTTTCCCTGGCCGAAATGGACAG

GAAATCTCGCCAATTGACGGCATCGCCGCTGAGACTCCCCCCTCCCCCGTCCTCCCCGTCCCAGCCCG

GCCATCACAGCCAATGACGGGCGGGCTCGCAGCGGCGCCGAGGGCGGGGCGCGGGCGCGCAGGTGCAG

CAGCGCGCGGGCCGGCCAAGAGGGCGGGGCGCGACGTCGGCCGTGCGGGGTCCCGGCGTCGGCGG
custom-character

ATGGCCGCCGCTGCTGCCGCGGCTCCCAGCGGCGGCGGT

GGAGGTGGTGAAGAAGAAAGACTTGAGGAGAAATCAGAGGACCAGGATCTCCAAGGTCTCAAGGATAA

GCCGTTGAAGTTCAAGAAGGTGAAGAAGGACAAGAAGGAAGAGAAAGAGGGCAAACACGAACCGGTCC

AACCTAGCGCTCATCATTCCGCCGAACCAGCAGAAGCGGGCAAAGCAGAAACGAGTGAAGGATCAGGT

AGCGCTCCTGCAGTTCCGGAAGCGAGCGCTTCACCGAAACAGCGCCGGTCTATCATCCGGGATCGGGG

ACCTATGTACGACGATCCAACGCTTCCGGAGGGATGGACGAGAAAGTTGAAGCAACGCAAGTCCGGAA

GAAGTGCTGGCAAGTACGATGTGTACCTGATTAACCCCCAAGGAAAGGCTTTCAGGTCTAAAGTAGAG

CTCATAGCTTATTTTGAAAAAGTGGGCGACACCTCTCTCGACCCTAACGATTTCGATTTCACCGTCAC

TGGCAGAGGCAGTCCTTCTAGACGCGAACAGAAACCCCCTAAAAAACCCAAGAGCCCCAAAGCCCCCG

GAACGGGACGAGGTCGCGGCCGCCCAAAGGGTAGCGGAACAACAAGACCAAAAGCGGCTACATCCGAA

GGTGTGCAAGTTAAGCGCGTGCTGGAAAAAAGCCCAGGAAAGCTCTTGGTCAAAATGCCATTCCAGAC

CTCACCTGGTGGCAAGGCAGAAGGTGGGGGCGCGACAACGTCCACCCAGGTAATGGTGATCAAAAGAC

CAGGCCGCAAGCGAAAGGCAGAGGCAGATCCGCAAGCGATCCCCAAAAAACGGGGCCGAAAGCCAGGA

AGTGTTGTCGCTGCTGCCGCGGCCGAAGCAAAGAAAAAAGCTGTCAAAGAGAGCTCCATTAGGTCAGT

ACAGGAAACCGTGCTGCCAATCAAAAAAAGAAAAACTCGGGAAACCGTCTCCATAGAAGTAAAGGAGG

TTGTCAAGCCCCTTCTTGTTTCCACCCTGGGAGAAAAATCAGGAAAAGGTCTCAAAACGTGTAAAAGC

CCGGGTCGAAAGTCAAAAGAATCATCACCAAAAGGCCGGAGTAGTTCAGCCAGTTCTCCGCCAAAGAA

AGAACACCACCACCATCACCACCACTCAGAATCCCCTAAGGCCCCAGTGCCTTTGCTCCCACCCCTTC

CTCCGCCGCCGCCAGAACCGGAGAGTTCTGAAGACCCCACTTCACCTCCGGAGCCACAGGACCTGTCC

TCTTCAGTTTGCAAAGAGGAGAAGATGCCTCGAGGCGGATCTCTGGAATCTGACGGGTGCCCGAAAGA

ACCCGCCAAGACGCAACCGGCGGTAGCAACCGCAGCAACCGCGGCCGAGAAATATAAGCATCGAGGAG

AAGGAGAACGCAAAGACATCGTTAGCTCTTCTATGCCACGGCCAAACCGGGAGGAACCAGTGGATTCA

CGAACGCCGGTCACAGAACGGGTCAGCGATTATAAGGACGATGACGACAAATA
custom-character

The LAMP2 protein sequence is:

(SEQ ID NO: 46)

MVCFRLFPVPGSGLVLVCLVLGAVRSYALELNLTDSENATCLYAKWQMNF

TVRYETTNKTYKTVTISDHGTVTYNGSICGDDQNGPKIAVQFGPGFSWIA

NFTKAASTYSIDSVSFSYNTGDNTTFPDAEDKGILTVDELLAIRIPLNDL

FRCNSLSTLEKNDVVQHYWDVLVQAFVQNGTVSTNEFLCDKDKTSTVAPT

IHTTVPSPTTTPTPKEKPEAGTYSVNNGNDTCLLATMGLQLNITODKVAS

VININPNTTHSTGSCRSHTALLRLNSSTIKYLDFVFAVKNENRFYLKEVN

ISMYLVNGSVFSIANNNLSYWDAPLGSSYMCNKEQTVSVSGAFQINTFDL

RVQPFNVTQGKYSTAEECSADSDLNFLIPVAVGVALGFLIIVVFISYMIG

RRKSRTGYQSVDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for LAMP2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

LAMP2-DNA

(SEQ ID NO: 47)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GTTTGTTAAAGAAGTGATTAATAAGACTGC

CACAGACCTACTGTTTCAGAATCTCTGGGGAATGAGGTACAGGAATCTGTATGTTAAAAAAAAAAAAC

CCAAAACCAGATGGTTCTTTTGGAAACTAACACTTGAGAATCAGTGCTTTATTCCAACTCAAGATTTT

TAAATGCTTTCATCTGTTGAATATTTTAGGTTTTGTCTGTTCATCTATCAAGTATAGCAAACAGTATG

CTTAGTATGAACTCATTACAGAATATTTGTGTGTATGTACATAGGAAAAATATCTGGAAGTATAGATG

TGGGTGTGTGTATATATGTGTGTAAATATATATAATAATGTTAATAGTAGGAATACAGATGATCTCTA

TTTTTCCGCTTTATCCTTCTGTTTTATTTCTCTCATTTTTTTCTTCCTGTGTTTAAAAAAGATGCTTC

TTGTTTCTGAGCTCAATTCCCCCACCTGAGAACAGGGTGCTGTAACTAGGTGAATTTCAAGATCATGT

CTTGTTCCGATGGTCCGTGACTCCATACTACCCCCTAGGTTCCCTCGTCCATCTCACAGCATGAACTG

CATAGGTAACAACAGTGTTTGGAGAATAAGCATGTATTATTTTTGTATGTATTACGTTTGAGATGCCT

AGCAACCGTTTTTGTGCCCGCAAAATTTTTCTCTTCTTTGTCAAGGAGCCAAAACGGAAATAGTCTAC

TATCTACGGCCCTCAAAAGTTCCTCCTCTCTCCTTAGCCTTAGAAAATACCGTCCGCCATAGGCATGG

GCAAAGACCTCATGGCTAAAACACCAAAAGCAATCGCAACAAAAGTCAAAATTGACAAATGGGATCTA

ATTAAAAGAACTTCTGCACAGCAAAAGAAATTAGCATTAGCGTGAACAGGCAACCTGCAGAATGGGAG

AAAATTTTTGCAATCTACCCATCTGACAAAGGTCTAATATCCAGAATCTACAAGGACCTTAAACAAAT

TTACAAGAAAAAAACAACCCCATCAAAAAGTGGGCAAAGGATATGACCAGACACTTCTCAAAAAAAGA

CATTTATGCAGCAACAAACATGAAAAAAAGCTCATTATCACTGATCATTAGAGAAAGGCAAATCAAAA

CCACAATGAGATACCATCTCACGCCAGTCAGAATGGTGATTATTAAAAAATCAGGAAACAATAGATGC

TGGCGAGGCTGAGGAAAAATAGGAATGCTTTTACACTGTTGGTGGGAGTGTAAATTAGTTCAACTATT

GTGGCAGACAGTGTGGCGATTCCTCAAAAATCTAGAACCAGAAATACCATTTGACGCATGCACACGTA

TGTTTATTGCAGCACTATTTACAATAGCAAAGACTTGGAACCAACCCAAATGCCCATCAATGATAGAC

TAGATAAAGAAAACGTGGCACATATATGCCATGGAATACTATGCAGCCATAAAAAAATGAGATCATGT

CCTTTGCAGGGACATGGATGAAGCTGGAAGCCATCATCCTTAGCAAACTAACACAGGAACAGAAAACA

AAACACTGCATGTTCTCACTCATAAGTGGGAGTTGAACAATGAGAACACATGGACACAGGGAGGGGAA

CAACACACACGGGGGCCTGTCAAGGGGTGGGGGCCAAGGGGAGGGAGAGCATTAGGAGAAATACCTAA

TGCATGTGGGGCTTAAAACCTAGATGACGGGTTGATAGGTGCAGTAAACCACCATGGCACATGTATAC

CTATGTAACAAAGCTGCACATTCTGCACATGTATCCCAGAACTTAAAGTAAAATTAAAAAAAAAAAAA

AAAAAGAAAGAAAAAGAAAAAGAAAATGCCGTCCGCGCATATCTCTCAGGAGCATAGGAAGGGCTGTG

AACCAAAAAGCCAGGGCGTGGTCGCCCCGCCCACCGGCCGCTACATCACCACCCCTCTCGCCGCTTTC

AAGCGCGGAGATTGGCTGTAAGCAAGAAAGAGCCCCGCCCC
custom-character

ATGGTCTGCTTTAGACTGTTTCCAGTACCAGGTTCTGGACTCGTGCTGGTGTGTCTTGTACTG

GGTGCAGTCCGATCTTACGCCTTGGAACTTAACCTCACTGATTCTGAGAATGCCACTTGTCTTTACGC

AAAGTGGCAGATGAACTTTACGGTGCGGTACGAGACCACGAATAAAACTTATAAGACCGTAACGATAA

GCGATCATGGGACCGTCACTTACAACGGCTCCATCTGCGGGGACGATCAAAATGGCCCAAAAATCGCT

GTCCAATTCGGCCCAGGGTTCAGTTGGATAGCCAACTTCACTAAAGCTGCATCAACCTATAGCATAGA

TTCTGTATCCTTCTCTTACAATACCGGAGATAACACAACGTTTCCCGATGCAGAAGACAAAGGCATAC

TCACCGTGGACGAGTTGCTTGCTATTAGGATACCGCTTAACGACTTGTTTCGCTGCAATAGTTTGAGC

ACCCTTGAAAAGAATGATGTGGTTCAGCATTATTGGGACGTACTCGTTCAAGCTTTTGTCCAGAATGG

TACGGTTTCAACCAATGAATTTCTCTGCGATAAGGACAAAACTTCCACAGTTGCCCCAACTATTCACA

CGACCGTTCCAAGCCCCACAACGACCCCGACTCCGAAAGAAAAACCAGAGGCCGGAACCTACTCAGTG

AATAATGGTAATGACACATGCCTCCTTGCTACGATGGGGCTCCAGTTGAACATCACACAAGACAAAGT

TGCGTCTGTCATAAATATTAACCCCAATACCACCCATAGTACCGGGTCCTGTCGATCTCATACTGCGC

TTCTCAGACTTAATAGCAGCACCATCAAGTACCTGGATTTCGTTTTCGCTGTAAAAAACGAGAATCGG

TTTTATCTCAAAGAAGTAAATATTAGTATGTACTTGGTAAATGGTAGTGTGTTCTCTATAGCGAACAA

TAACCTCTCATACTGGGATGCGCCTCTTGGTAGTTCCTACATGTGCAACAAGGAGCAAACAGTGAGTG

TCAGTGGGGCATTTCAAATCAATACGTTTGATCTTAGAGTCCAGCCATTCAATGTGACTCAGGGGAAG

TACTCTACGGCGGAAGAGTGTTCCGCGGACTCCGATCTTAATTTTTTGATCCCTGTCGCCGTGGGGGT

CGCCCTGGGATTTCTGATAATTGTCGTTTTTATAAGCTACATGATAGGCAGGAGGAAGAGTCGGACGG

GATACCAGTCTGTGGATTACAAAGATGATGATGACAAATA
custom-character

The NAGLU protein sequence is:

(SEQ ID NO: 48)

MEAVAVAAAVGVLLLAGAGGAAGDEAREAAAVRALVARLLGPGPAADFS

VSVERALAAKPGLDTYSLGGGGAARVRVRGSTGVAAAAGLHRYLRDFCG

CHVAWSGSQLRLPRPLPAVPGELTEATPNRYRYYONVCTQSYSFVWWDW

ARWEREIDWMALNGINLALAWSGQEAIWQRVYLALGLTQAEINEFFTGP

AFLAWGRMGNLHTWDGPLPPSWHIKQLYLQHRVLDQMRSFGMTPVLPAF

AGHVPEAVTRVFPQVNVTKMGSWGHFNCSYSCSFLLAPEDPIFPIIGSL

FLRELIKEFGTDHIYGADTFNEMQPPSSEPSYLAAATTAVYEAMTAVDT

EAVWLLQGWLFQHQPQFWGPAQIRAVLGAVPRGRLLVLDLFAESQPVYT

RTASFQGQPFIWCMLHNFGGNHGLFGALEAVNGGPEAARLFPNSTMVGT

GMAPEGISQNEVVYSLMAELGWRKDPVPDLAAWVTSFAARRYGVSHPDA

GAAWRLLLRSVYNCSGEACRGHNRSPLVRRPSLQMNTSIWYNRSDVFEA

WRLLLTSAPSLATSPAFRYDLLDLTRQAVQELVSLYYEEARSAYLSKEL

ASLLRAGGVLAYELLPALDEVLASDSRFLLGSWLEQARAAAVSEAEADF

YEQNSRYQLTLWGPEGNILDYANKQLAGLVANYYTPRWRLFLEALVDSV

AQGIPFQQHQFDKNVFQLEQAFVLSKQRYPSQPRGDTVDLAKKIFLKYY

PRWVAGSWDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NAGLU and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

NAGLU -DNA

(SEQ ID NO: 49)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GGACAACATGGTGAAATCCCATCCCTACAA

AGGTTAACTGGGCTTGGTGGCACGTGCCTGTAATCCCAGCTACTCAGGAGACTGAGACAGGAGAATGG

CTTGAACCTGGGTGGCTGAGGTTCCCGTGAGCTGAGATTAAAAAAAAAAATCATACTTCCCTAGTATC

TAAAGTTGATATCTGATTCCAGGCCTCTTTCAACTTTTTTTGTTTGTTTGTTTGTTTTTTTGATATGG

AGTCTCGCTCTGTCATCCAGGCTGGAATGCAAATGGCACGATCTTGGCTCACTGCAACTTCCACCTCC

AGCGTTCAAGCGATTCTCCTGCCTCAGCTTCCCAAGTAGCTGGGACTACAGGCGTGTGCCACCAAGCC

TGGCTAACTTTTTTTCTTTTTTTTTTTTTTGAGAGGGAGTCTTGCTCTGTCCCCCAGGCTGGAGTGCA

GTGGTGTGATCTTGGCTCACTGCAACCTCCGCCTCTCCGGTTCACGCCATTCTCCTGCCTTAGCCTCC

CGAGTAGCTGGGAGTACAGGCGCTCGCCAACACGCCCGGCTAATTTTTTGTATTTTTAGTAGAGATGG

AGTTTCACCGTGTTAGCCAGGAGGGTCTTGATCTCCTGACCTCGTATCCGCCCGTCTTGGCCTCCCAA

AGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCAGCACCTGGCTAACTTTTGTATTTTTAGTACAGA

CGGGGTTTCACTGTATGTTGGCCAGGCTGGTCTCAAACCCCTGACTTGAGGTGATCTGCAAGCCTCAG

CCTCCCAGAGTGCTGGGATTACAGGCGTAAGCCACCGCTCCTGGCCTAAGGTTGGCTATTTTTATGGT

TATTTCTTGATTATATGATAAACAAGGGGTGGGTTAGTAATGAATTTTTCAGAAAAGGGGTGGGGATC

CCCCCCAACTGAAGGTTCCTCCACTGTTTAGACCATATAGGGTAACTTCTGGACGTTGCCATGGCATT

TGTAAACTGCCTGGCGCTGCTAGGAGTGTCTTTAGCATACTAATGCATTATAATTAGCGTATAATGAG

CAGTGAGGACGATCAGAGGTCACCTTCCTGTCTTGGTTTTGGCAGGTTTTGACCAGTTTCTTTGCTGC

ATTCTGTTTTATCAGCGGGGTCTTGTGACCTTTTATCTTGTGCTGACCTCCTGTCTCATCCTGTGACG

AAGGCCTAACCTCCTGGGAATTCAGCCCAGCAGGTCTCTGCCTCATTTTACCCAGCCCCTGTTCAAGA

TGGAGTCGCTCTGGTTGGAAACTTCTGACAAAATGACAGCTCCTGTTATGTTGCTGCTGCTGCCGCCA

ATGGACAGCCTTTAACGTGCCCGCCAGCCCTGCTCCACCGCCGGCCTGGGCTCACATGGCCCCATCCC

TCCTCGAACCTCCTAGCCTGTTAGTTACTCAAATCTGCAAGCTCTCTGCCTTCTCAGGGCCTTCAATA

AATGCATTTCTTCTGTCTGGAAGGCTCTTCCTTTCCCTCTTCTAGCCAATTCCTATTCATCCCTGAGT

TTCAGATTAAAAGTCACTTCCTTTGGAAACCTTACTTCGCTACTTCGCTACTTACTGCACTACTTCGC

AGCATCACAACTATGATGGAAATCCTTACTTACGTTAAATATCTGGTTTCTAGGTCACCTCCCTGACG

GGGACGGTAGGGACCGTCTTCTCGTTCATCAGTAGGGAAGTAGCTATGGCAGTGCCTGATACAAAATA

AACTCCAAATGTGTATTTATTAGATGGTTGGATGGAAGTTATTTGCGTGTGAAAGCGCGTTTTACCCG

AAGGCGCTCTGTGAGGGCCAGCGGGTCCCCTTCGGCCCTGGAGCCGGGGTCACACGCTCCCCACCGCG

TGCGGTCACGAGACGCCCCCAAGGGAGTATCCTGGTACCCGGAAGCCGCGACTCCTGGCCCTGAGCCC

GGGCTTAGCCTTCGGGTCCACGTGGCCGGAGGCCGGCAGCTGATTGGACGCGGGCCGCCCCACC
custom-character

ATGGAGGCGGTAGCCGTTGCCGCTGCCGTCGGAGTACTT

TTGCTCGCAGGAGCAGGTGGTGCAGCTGGTGACGAGGCTCGGGAGGCAGCGGCCGTACGCGCACTGGT

AGCTCGGCTGCTGGGGCCAGGTCCCGCAGCTGACTTTAGCGTGAGTGTGGAGCGGGCCCTCGCTGCGA

AGCCAGGCCTTGATACCTACTCTCTGGGCGGGGGAGGAGCGGCACGCGTGAGAGTTCGGGGAAGTACC

GGGGTGGCTGCGGCGGCGGGCTTGCATCGGTATCTTAGGGACTTTTGTGGGTGTCACGTCGCCTGGTC

AGGTAGCCAACTCAGGCTGCCACGACCTTTGCCAGCAGTACCCGGCGAGTTGACGGAAGCGACGCCAA

ATAGGTATAGGTACTATCAAAACGTCTGTACCCAGTCTTATTCTTTTGTATGGTGGGATTGGGCTCGC

TGGGAACGAGAAATAGACTGGATGGCACTTAACGGCATCAATCTTGCGTTGGCCTGGAGCGGGCAGGA

GGCAATCTGGCAGCGAGTGTATCTCGCATTGGGGCTCACACAGGCTGAAATAAATGAGTTTTTTACCG

GTCCCGCCTTCTTGGCTTGGGGCAGGATGGGTAATCTCCATACGTGGGATGGACCGCTCCCACCTTCA

TGGCATATAAAGCAGCTGTACCTGCAACATAGGGTGTTGGACCAAATGAGGAGCTTTGGAATGACACC

GGTACTTCCGGCATTCGCCGGTCACGTTCCTGAAGCGGTCACGCGAGTATTTCCGCAAGTGAATGTAA

CAAAGATGGGTTCATGGGGACACTTCAATTGTTCATATTCATGCTCTTTCCTGCTTGCGCCGGAAGAT

CCTATTTTTCCTATCATTGGAAGTCTGTTCCTTCGGGAATTGATCAAGGAGTTTGGAACAGATCACAT

ATATGGAGCAGACACTTTTAACGAAATGCAACCTCCGTCTAGCGAGCCCTCTTATCTGGCAGCTGCGA

CCACGGCGGTGTATGAAGCGATGACAGCTGTCGATACGGAAGCAGTCTGGCTCCTTCAAGGTTGGCTG

TTTCAACACCAACCGCAATTTTGGGGACCAGCCCAGATTAGGGCTGTGTTGGGTGCTGTGCCCCGGGG

TAGGCTCTTGGTGTTGGATCTTTTTGCGGAGAGTCAGCCTGTGTATACCCGAACGGCGAGCTTTCAAG

GTCAGCCGTTTATCTGGTGTATGCTTCATAACTTTGGCGGGAACCATGGTCTTTTCGGTGCCCTTGAA

GCCGTAAATGGGGGGCCAGAGGCTGCTCGATTGTTTCCTAACAGCACTATGGTAGGAACAGGTATGGC

ACCCGAGGGTATTAGTCAAAATGAGGTCGTATACAGTTTGATGGCAGAACTTGGGTGGCGCAAAGATC

CCGTACCTGATCTGGCAGCGTGGGTTACGAGCTTCGCGGCTCGAAGGTACGGAGTAAGTCACCCAGAC

GCTGGGGCCGCCTGGCGGTTGCTCCTGCGATCCGTCTACAACTGCTCAGGTGAGGCATGCCGCGGGCA

CAATAGAAGCCCACTCGTCCGACGACCATCCCTTCAAATGAACACTAGTATCTGGTACAACAGGTCTG

ACGTATTCGAGGCATGGCGCCTCCTCCTCACTAGCGCACCGAGTCTGGCTACCTCCCCCGCGTTTAGG

TACGACCTTCTGGACTTGACCAGACAAGCTGTGCAGGAGCTCGTGTCACTTTACTACGAAGAGGCCAG

ATCTGCATATCTGTCTAAGGAACTGGCATCCTTGCTTAGAGCGGGTGGGGTTCTGGCTTACGAACTCC

TTCCAGCACTGGACGAGGTGCTCGCGAGTGACAGTAGGTTTCTCCTCGGGTCATGGCTGGAACAAGCA

AGGGCCGCGGCCGTTTCTGAAGCCGAGGCTGACTTTTACGAACAGAACTCTCGATACCAGTTGACGCT

GTGGGGACCCGAGGGGAATATCTTGGATTACGCGAACAAGCAGCTGGCAGGTCTGGTAGCCAACTACT

ATACGCCGAGGTGGAGGCTCTTCCTCGAGGCTCTTGTCGATTCCGTCGCCCAAGGGATACCCTTTCAG

CAGCACCAATTCGACAAGAACGTTTTTCAACTGGAACAGGCTTTCGTACTTTCCAAACAACGCTATCC

CAGCCAGCCTCGGGGTGACACAGTTGACCTGGCAAAAAAAATCTTCCTTAAATACTATCCAAGATGGG

TCGCCGGTAGTTGGGATTATAAAGATGATGATGACAAGTA
custom-character

The ARSB protein sequence is:

(SEQ ID NO: 50)

MGPRGAASLPRGPGPRRLLLPVVLPLLLLLLLAPPGSGAGASRPPHLVFLL

ADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYYTQPLCTPSRSQLLTGR

YQIRTGLQHQIIWPCQPSCVPLDEKLLPQLLKEAGYTTHMVGKWHLGMYRK

ECLPTRRGFDTYFGYLLGSEDYYSHERCTLIDALNVTRCALDFRDGEEVAT

GYKNMYSTNIFTKRAIALITNHPPEKPLFLYLALQSVHEPLQVPEEYLKPY

DFIQDKNRHHYAGMVSLMDEAVGNVTAALKSSGLWNNTVFIFSTDNGGQTL

AGGNNWPLRGRKWSLWEGGVRGVGFVASPLLKQKGVKNRELIHISDWLPTL

VKLARGHTNGTKPLDGFDVWKTISEGSPSPRIELLHNIDPNFVDSSPCPRN

SMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQYNV

SEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSV

PVYFPAQDPRCDPKATGVWGPWMDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for ARSB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

ARSB-DNA

(SEQ ID NO: 51)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AAATATTTATTAATTACAAGAAGAAAATAT

TAACCTTACAATGAGGAAATGTTTACCTTAACAAAGTTATCCCATAAGAAAGCAATTCAGCATCATGT

GCCTCTTAATAGGAAGCACCGAGAAACATACCACATCACTTTTTGTGGTATTCCTGCACAAATCCATA

ACCTCTATCTAATTGTGAAGAAACATCAAACTCCAATTGAGAGATTTTATAAAATAACTAGCTTGTAC

TGCACATTATGTGTTCAATACATAGATGGAAAATAGAATTAACTCTTCAATTTGCACATTTCCAGAGC

ACTATTAACATATGCTTTTATTTTAAAAACATAGGACGTAAGAATCTGTGCAAGTTTAGCTAGTTTCA

GGGGAAGTTGGTTAAAGGAGGAATTGTTCCTGCAGATTAGCACCCATCAATTATTTCTTCTTAATTTT

TATCAAGGAGAATAGGAAGGATTACGGGGGAGAAAGACACAAAACCACAGCGGAAATTCTCAGTCCTT

CAAGGTCTTCTACAGGGTGTTTAAATGAAAAGTTCAACCCTTGACATAATGAGTCAAACAGTTCTCTC

AAAAGTTATTCTTTGAATTTAATGCTAAAATTTTCACTTTTTTCTGCTAAATTTCATTGATTCCACTA

GAGATTAAAGTGCATACAACATAAACTAATCTACTTCATGCAAAGAAAAAAAGTGTATGTAAGAGGCA

AACATTTCATGTGTTAAAGGATTCTTGGGGAAAAAAAGGTAAAATCATGACCCTCATACAAATATAAA

AGTGAATACATGATTTTATTTAACTCATTAATAAGGAAATTGGTAAGGTGTTAAAACCAATTCAAAGG

ACAATCCAAAGAACAGATCAGGAATACTAAAATAAATATGCAAGCGGAGGTGAAACTGTTTTCCTTGG

TAGTGGTGGAGGGGAAGGATTGCTACTCCGCTGGATAAAGTTCATTTGTGTATATATAAATAAGAATT

ATTTTCCATTGTTATTTATCTATAACTTATAAAGTTGTAAACAACTTCCACGGAATCAGACTCAACCT

GGAAGGGTATGGTCTCTAGGCAATGCAAAAATTTTCCCCTACACCTGTTAACAACTATAATATCTCCA

GACAGAGTAGACAGAAAGTCTGGATGGCAACGGGAATCTACTGGTCATACGGCTAACTTCCTAATTCA

ATAAGCACGTGACTAAAGGATTTTTTCCTTCCACTCAGATATTTCAGGCTAACTAGATACTGTGTGCT

TCTTAGTGTCACTGCTTAGTGGGGGAGCCAGCTCTGAGTGGGGTCATATCCGGACAAGCGAATGAGCT

ATTTATTCAATGACCACGCAACACTCCAAATCCTCCCAGGGCAACTTGAAAGTAACCGCACCTTCCAA

AGGGCACCGTGCAATCAGACTGTGTGTTTGGCCTCCTGTTTGCTAGTGGGGAGGAAGCGGCTTCATGG

GTGTACACTACGCATAAATGAATGTGAAAGGCTATTTAGACCTCTGCCTTTTCACCGTCCTCCCACCT

GCCACAGGCTGGGCTCTTGTGCTAGAAATGACTTGCTAGCTAGACATCATGGTTCAGGATCTGAGTCA

GAGGTTTAACCATTTATAAGCTTTTTTCTTATGAAAAATTGGCACTAATTATAATGTCTAACTGTCAG

AGTTGTTGCAGGCTTTACAGGAGACGCGGGCTGTGAAGATGCTTTGTAAATTGTGAAGCGTTATTAAA

GAACACATCTTTTTTTTTTAGGAAACCACAGTGCAAATTTAATTGCCGGGGAAGATAACGGGCCTTGG

TGCCCTCCAAGCGTCAGCTGAGTTTCCAAGAAGCCGGGCAGCGGGCGCCCGCGGGTTCGTCTCTGGCT

CCTCCTCCGCCACAGCAGCCGGGGGCCCGGGTCGGAGGCGGCGGGGGCCGAGCGCCCGGCCTCGCAAG

CCCACGGCCCGCTGGGGGTGCCGTCCCGCGCCGGGGCGGAGCAGGCCCCGGCAGCCCAGTTCCT
custom-character

ATGGGCCCCCGGGGCGCAGCGAGCCTCCCCAGAGGGCCAGG

ACCAAGGAGGCTCCTTTTGCCAGTCGTCTTGCCGCTTTTGCTCCTTTTGCTTCTCGCGCCACCCGGCA

GTGGGGCAGGAGCTTCTCGCCCACCTCACCTTGTCTTCCTGCTTGCTGACGACCTTGGATGGAATGAT

GTGGGTTTTCACGGTTCCCGGATTCGAACACCACACTTGGATGCTCTGGCTGCGGGGGGCGTACTGCT

CGATAATTATTACACACAACCGTTGTGCACACCGTCTCGGAGTCAGCTTCTGACGGGACGATATCAAA

TAAGGACTGGGCTGCAACATCAGATTATATGGCCATGTCAACCCAGTTGCGTGCCCCTTGACGAGAAA

CTCCTGCCTCAGCTGTTGAAGGAGGCTGGATACACGACACATATGGTCGGCAAGTGGCATCTGGGAAT

GTACAGGAAAGAGTGTCTCCCAACCCGGCGCGGATTCGATACGTATTTTGGGTACTTGTTGGGCTCAG

AAGATTACTATTCACACGAAAGGTGCACTCTTATCGACGCACTCAACGTTACGCGCTGCGCACTTGAT

TTCCGAGATGGAGAGGAAGTTGCAACTGGGTATAAGAATATGTATTCAACAAACATCTTTACTAAGCG

GGCAATAGCCCTCATTACTAATCATCCCCCCGAAAAACCGCTGTTTCTCTATCTCGCCCTGCAGTCAG

TCCATGAGCCGCTGCAGGTGCCTGAGGAGTACCTCAAACCATACGACTTCATACAAGATAAGAACCGA

CACCATTATGCGGGTATGGTCTCTCTGATGGACGAGGCTGTCGGGAATGTTACTGCAGCATTGAAATC

TTCCGGCCTTTGGAACAACACAGTCTTCATATTTTCTACGGACAATGGCGGGCAGACTCTTGCCGGTG

GCAATAACTGGCCTCTTAGGGGTCGCAAGTGGTCCCTCTGGGAAGGAGGCGTCCGCGGTGTAGGGTTT

GTAGCGAGCCCCCTCCTTAAACAAAAAGGAGTTAAAAACAGGGAACTTATTCACATTTCCGATTGGTT

GCCCACGCTCGTCAAGCTCGCGAGGGGTCATACAAACGGGACAAAACCGCTTGACGGGTTTGATGTAT

GGAAAACCATTTCTGAGGGGTCTCCTAGCCCCAGGATCGAGCTGTTGCATAACATAGACCCAAACTTT

GTAGACTCCTCACCCTGTCCCCGAAATTCAATGGCCCCTGCCAAAGATGATTCATCCCTCCCTGAGTA

CTCCGCTTTTAACACAAGCGTACATGCCGCTATTAGGCACGGCAATTGGAAGCTGCTGACCGGGTATC

CTGGTTGTGGTTATTGGTTCCCTCCCCCCTCACAATACAACGTGTCTGAAATACCGAGTAGTGATCCG

CCGACAAAAACCCTGTGGCTGTTCGATATTGATCGAGACCCTGAAGAACGCCACGATCTCTCCCGGGA

ATACCCCCACATTGTCACCAAGCTTCTTTCACGATTGCAATTTTACCACAAGCATTCAGTACCCGTTT

ACTTCCCCGCCCAGGACCCAAGGTGCGATCCTAAAGCAACGGGGGTTTGGGGACCATGGATGGACTAC

AAAGATGATGACGATAAATAG
custom-character

The GUSB protein sequence is:

(SEQ ID NO: 52)

MARGSAVAWAALGPLLWGCALGLQGGMLYPQESPSRECKELDGLWSFRAD

FSDNRRRGFEEQWYRRPLWESGPTVDMPVPSSFNDISQDWRLRHFVGWVW

YEREVILPERWTQDLRTRVVLRIGSAHSYAIVWVNGVDTLEHEGGYLPFE

ADISNLVQVGPLPSRLRITIAINNTLTPTTLPPGTIQYLTDTSKYPKGYF

VQNTYFDFFNYAGLQRSVLLYTTPTTYIDDITVTTSVEQDSGLVNYQISV

KGSNLFKLEVRLLDAENKVVANGTGTQGQLKVPGVSLWWPYLMHERPAYL

YSLEVQLTAQTSLGPVSDFYTLPVGIRTVAVTKSQFLINGKPFYFHGVNK

HEDADIRGKGFDWPLLVKDFNLLRWLGANAFRTSHYPYAEEVMQMCDRYG

IVVIDECPGVGLALPQFFNNVSLHHHMQVMEEVVRRDKNHPAVVMWSVAN

EPASHLESAGYYLKMVIAHTKSLDPSRPVTFVSNSNYAADKGAPYVDVIC

LNSYYSWYHDYGHLELIQLQLATQFENWYKKYQKPIIQSEYGAETIAGFH

QDPPLMFTEEYQKSLLEQYHLGLDQKRRKYVVGELIWNFADFMTEQSPTR

VLGNKKGIFTRQRQPKSAAFLLRERYWKIANETRYPHSVAKSOCLENSLF

TDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GUSB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GUSB-DNA

(SEQ ID NO: 53)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TGCCCAGCTAAATATGGAGATGCGGTTTCT

CCATATTGGTCAGGCTGGTCTCGAACTCCCAACCTCAGGTGATCTGCCTGCTTCAGCCTCCCAAAGTG

CTGGGATGACAGGCGTGAGCCACCGCACCTGGCCAAGGCACTTGGTTTCTTAGATCACCCACTTGGCC

CTCTTCCAAGTTGTACTTTCCTTCTTTCCTTCCTGTTCTAAAGTTTTTTAATATTTTTTTTTTTCCTG

AAATGGCATCTCACTCTGTAGCCCAGGCTGGAGTGCGGTGGCGTGATCTCAGCTCACTGCAACCTCTG

CCTCCTGGGTTAAAGCATTTCTCCTGCCTCAGCCTCCCAAATAGTAGGGATTACAGGTGCCTGCCACC

ACGCCTGGCTAATTTTTGTATTTTTAGTAGAGATGGGGTTTCTCCACGTTGGCCAGGTTGGTCTCAAA

CTCCTGATATCAAGTGATCCTCCCGCCTTGGCCTCCCAAAGTGCTGGAGTTTGGAGTTACAGGCCTGA

ACCTCTGTGCCTGGCCTGCTTTTTTTTTTAGACTGAGTCTTGCTCTCTCGCCAGGCTGTAGTGCTGTG

GTGCGATCTCGGCTGACTGCAACCTCTGCCTCCCGCGTTCAATCGATTCTCCTGCCTCAGCCTCCCGA

GTAGCTGGGACTACGGGCGCATGCCACCATGCCCAGCTAATTTTTTAGTAGAGATGGGGTTTCATCAT

ATTGGCCAGGCTGGTCTCAAACCCCTGACCTCGTGATCCCCCCACCTCCGCCTCCCAAAGTGCTGGGA

TTACAGGTGTGAGCCACTACGCTCAGCACTGGCCTGCTTTTTAACAAGCTTTTACTACTGCTCTGCAG

CTTACCTCCCTCTGGCTTTCTGCCTTATGCCCCTCAGTGCAATTCTTTCTTCTGAGGAGGCAAGAATT

GAGGTTGTTGCTGATGTGTAGGGATTCACCACCCGGAACTCCACCAGTAACAGGTCGAGGATGCTAGT

TGAAAATGTTATGTAAGCTGCATGCTTTTTACAAATGGTAGTGGTTCTCATGTCCAGCAATGGCCACT

GCACCGTCCCTGTATGAAAGTCCCCTCCATAAATCTATGTCTCCTTTGCTGTCTCCAGATCTCCTCCT

CTACCTCTCCCACACGGTGCCTTCCCTACTGGAGTAAACTGGGGTCCCGCAGGGCACCCTTTCCCTGC

AATTTTTTTTTTTTTTTTGAGACAGAGTCTCGCTCTGTTGCCCAGGCTGGAGTGCAGTGGTGCGATCT

CGGCTTACTGCAGCCTTTGCCTCCCGGGTTCAAGCGATTCTCCTACCTCAGCTTCCTGAGTAGCTGGG

ATTACAGGCACGCACCATCACGCCCCGCTAATTCTTTTTTTTTTTTTTGTATGTTTACAAAATAGGGA

CGGGGTTTCACTATCGTTGGCCAGGCTGGTCTCGAACTCCTGGCCTCAAGTGATCTGCCCCCCTCGGG

TTCCCAAAGTGCACCTGGCCTCTCTCCCTGCATCTTTATGTGCCTGCAACACCAAGAGGGAGCTCTTG

GCCCCTGGGTTAAGGTCAGGGCTCCAGAAGCCCAGGGTCAAGGCTATGGCCGCATCCCAAGGACGTGC

ATCCCTGCAAGAGGCTGCATCAGACAGGCATGGAAGAGGCGCCGCTGGGGCCTCCTTGAATTCCTGCT

GGGAAAAGCAAGTGGAGGTGCTCCTTGAAGAAACAGGGGGATCCCACCGATCTCAGGGGTTCTGTTCT

GGCCTGCGGCCCTGGATCGTCCAGCCTGGGTCGGGGTGGGGAGCAGACCTCGCCCTTATCGGCTGGGG

CTGAGGGTGAGGGTCCCGTTTCCCCAAAGGCCTAGCCTGGGGTTCCAGCCACAAGCCCTACCGGGCAG

CGCCCGGCCCCGCCCCTCCAGGCCTGGCACTCGTCCTCAACCAAGATGGCGCGGATGGCTTCAGGCGC

ATCACGACACCGGCGCGTCACGCGACCCGCCCTACGGGCACCTCCCGCGCTTTTCTTAGCGCCG
custom-character

ATGGCGAGAGGCAGTGCAGTAGCCTGGGCTGCTTTGGGACC

ATTGTTGTGGGGGTGCGCTCTCGGACTTCAGGGCGGTATGCTCTACCCTCAAGAGAGTCCCTCCAGGG

AATGTAAGGAGTTGGACGGCCTCTGGTCCTTCAGAGCCGATTTCAGTGACAATCGCCGCAGAGGGTTC

GAGGAGCAGTGGTACCGCCGACCGCTCTGGGAGTCAGGCCCAACCGTAGACATGCCAGTCCCATCTTC

ATTCAATGACATAAGCCAGGACTGGAGGCTGCGACACTTCGTCGGGTGGGTATGGTATGAGCGCGAAG

TGATCCTCCCTGAACGGTGGACTCAGGACTTGCGGACGAGGGTAGTACTTCGGATAGGTAGTGCTCAC

TCCTATGCTATTGTCTGGGTGAACGGAGTGGATACTCTGGAGCATGAGGGTGGCTATCTTCCTTTTGA

AGCTGACATCAGTAACCTGGTGCAAGTGGGGCCGCTGCCTTCCAGACTGCGAATCACCATCGCTATCA

ATAATACTCTGACCCCCACTACGTTGCCGCCAGGCACCATCCAGTATTTGACCGACACCTCTAAATAC

CCCAAGGGCTATTTTGTGCAAAACACTTACTTTGATTTCTTCAACTATGCCGGCCTGCAAAGATCTGT

GCTGCTTTACACCACTCCGACGACCTATATAGATGACATAACCGTGACGACGAGTGTCGAACAAGACT

CAGGTCTCGTCAACTACCAGATTAGTGTAAAAGGCAGTAATCTTTTTAAGCTCGAAGTGAGGCTTTTG

GATGCTGAAAATAAGGTGGTGGCAAATGGAACGGGCACACAAGGCCAACTTAAAGTGCCGGGGGTAAG

TCTGTGGTGGCCGTATCTTATGCATGAACGACCCGCTTATCTCTACAGTCTCGAAGTCCAATTGACGG

CACAAACAAGTCTTGGTCCTGTGAGTGATTTCTATACGTTGCCTGTGGGCATAAGGACTGTAGCTGTG

ACAAAGTCCCAATTTCTTATAAACGGTAAGCCCTTCTACTTTCATGGCGTCAACAAACATGAGGACGC

TGATATTCGCGGAAAAGGGTTTGATTGGCCTCTCCTGGTCAAGGACTTCAACCTTCTCAGATGGTTGG

GCGCGAACGCCTTTAGAACAAGCCACTATCCGTATGCAGAGGAGGTCATGCAAATGTGCGACAGATAT

GGGATTGTTGTAATCGATGAATGTCCCGGCGTGGGCTTGGCGCTCCCCCAATTTTTTAATAACGTGTC

TCTTCACCACCATATGCAAGTAATGGAGGAGGTAGTACGCCGCGACAAGAACCACCCCGCGGTAGTTA

TGTGGTCAGTAGCGAATGAACCAGCTTCTCATCTGGAAAGTGCCGGTTACTACCTCAAGATGGTGATA

GCCCATACAAAGTCTCTCGACCCTTCCCGCCCCGTGACATTCGTATCAAACAGCAATTATGCAGCCGA

TAAAGGCGCCCCATACGTAGACGTTATATGTCTTAATAGCTATTACTCCTGGTATCACGACTACGGTC

ATTTGGAACTCATTCAGCTGCAGCTCGCCACGCAATTCGAGAACTGGTACAAGAAATATCAGAAGCCA

ATTATACAGAGTGAATATGGTGCTGAAACAATCGCTGGATTCCATCAAGACCCACCATTGATGTTTAC

CGAGGAGTACCAGAAAAGTCTCCTCGAGCAATATCATCTTGGACTGGACCAAAAGCGACGAAAATACG

TAGTAGGGGAACTTATTTGGAATTTTGCCGATTTTATGACGGAACAGAGCCCTACACGAGTTTTGGGG

AACAAAAAGGGCATTTTCACCCGGCAACGGCAACCCAAGAGTGCCGCCTTCCTTCTTAGAGAAAGATA

CTGGAAGATTGCTAACGAAACACGCTATCCCCACTCTGTTGCTAAGAGCCAATGCTTGGAAAACTCCT

TGTTTACAGACTACAAGGATGATGACGATAAATA
custom-character

The SLC19A3 protein sequence is:

(SEQ ID NO: 54)

MDCYRTSLSSSWIYPTVILCLFGEFSMMRPSEPF

LIPYLSGPDKNLTSAEITNEIFPVWTYSYLVLLL

PVFVLTDYVRYKPVIILQGISFIITWLLLLFGQG

VKTMQVVEFFYGMVTAAEVAYYAYIYSVVSPEHY

QRVSGYCRSVTLAAYTAGSVLAQLLVSLANMSYF

YLNVISLASVSVAFLFSLFLPMPKKSMFFHAKPS

REIKKSSSVNPVLEETHEGEAPGCEEQKPTSEIL

STSGKLNKGQLNSLKPSNVTVDVFVQWFQDLKEC

YSSKRLFYWSLWWAFATAGFNQVLNYVQILWDYK

APSQDSSIYNGAVEAIATFGGAVAAFAVGYVKVN

WDLLGELALVVFSVVNAGSLFLMHYTANIWACYA

GYLIFKSSYMLLITIAVFQIAVNLNVERYALVFG

INTFIALVIQTIMTVIVVDQRGLNLPVSIQFLVY

GSYFAVIAGIFLMRSMYITYSTKSQKDVQSPAPS

ENPDVSHPEEESNIIMSTKLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SLC19A3 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SLC19A-DNA

(SEQ ID NO: 55)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCG
CTATTACCATGCTATGCATGAATGAATGAATTCCTCAATAT

CTCTCTCTGATTTAGACTGTGGCTATGAGATATTAGAGAATCAGAGTAAACTTCTCAAGGTCCAATTT

GAACTCATTTTCTTCAAGAGGTGTGAAGGAAATCATGACACCTTCAGCCTTTAAGAAAATTTCACAAT

ATTCTTTGGGAGGACCCAGCAATTTGCAAGGTTGCACAATGAGCAGGGCACTCCTACACCTAAGGTTC

AGCTCAGGACTTTTCACAAATCATAGGAAGATGAAAATAGAAAACGCAGAGTCGTAGGACAGAGAACC

AAGACACCTCGGGGTGTTTTAATCCATTTCACTTCCACTGGTAGCCCTTAGAAGCCACGCAGTGTTTA

TCTTTAGGGAGGGTTTTTCAAGTCCACCAAGAGATGAACAGAAATAAAAATATTTTTTCCATTTTAAC

CAATAAGAACCTTGTAATGCTTTAAAAAAATTCTCTGTTTAATAAGAAGTTTCACTTTAATATATAAA

CTCTTTGCAGGCTAAGCGTAGTGGCTCATGCCTGTAATCCCAACACTTTGGGCGGGCAAGGCAGGAGG

ATCCTTTGAGCCCAGGAGTTCAAGACCAGCCTGGGCAAGATAGTGAGACTCTGTCTCTACCAAAAAAA

AAAAACAAAAAAATTAATGTGACGTGGTGGCACCCACCTGCAAGCCCAGCTACTTGGGAGGCTGAGGC

AGGAGGATCAGTGTGCCTGGGAGATTGAGGTTGCAGTGAGCTGGGGTTGCACCACTGCACTCCAGCCT

GGGAGATAAAGTGAGACTTTGTCAAAAAAAAAAAAAAAAGAAAGAAAGAAAGAGAAAAGAAAAGAAAA

GAGGCCAGGTGGCCGGGTGCTGTGGCTCACACCTGTAATCCTAGCACTTTGGGAGGCCGAGGCGGGTG

GATCACCTGAGGTCAGGAGTTTGAGACCAGCCTGGACAACATGGTGAAACCCCATCTCTACTAAAAAT

ACAAAAATTAGCTGGGTGTGGTGACGGGCGCCTGTAATCCCAGCTACTAGGGAGGCTGAGGCAGAAGA

ATTGCTGGAACCCGGGAGGTGGAGGTTGCAGTGAGCCAAGATCGTGCCATTGCACTCCAGCCCGGGGC

CAACAACAGCGAGGCTCCATCTCAAAAAAAAAAAGAAAGAAAGAAAGAAAGAAAAAAGACCAGGCGCG

GTGGCTCACGCCTGTAATCTCAGCACTTTGAGAGGCCGAGGCAGGCGGATCACGAGGCCAGGAGTTCG

AGATGAGCCTGGCCAATATGGTGAAACCAAACCCCGTCTCTACTAAAAACACAAAAATTAACTGGGCG

TTAATTTTTGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGGTTGTAGTGAGCCGAG

ATCGCGCCACTGCACTCCATCCTGGGCGACAGAGGGAGACTCTGTCTCAAAAAAAAAAAAAAGAAAGA

AAGAAAAGAGAAAAGAAAAGAAAAAGAAGAAGAAAAGAAAAAATTGTTTGTATCAGATTTTCAAAGTG

CCAGGAAACCATCCCACTCTACCTCCTTTAAAAAAAAAAAGTGCAGAGTGATTATAACCACTGGCTCT

GGAGCCAGGAGCCCCAACTAAAACCCAGGCTTCTCTATTTACTAGGCCTACTTCCTTCCGCCTCACTT

TCTTCATGTGTAGAGTGGGGGTGACAGCCAGCCAGCCCTCTCTCCTAAGCTTTTGGAGAGAAATAAAT

GGATTCATAAGAAAGGACATATTTGTAAATAAAGCAAACGATCGCTGTTGGATTCAGGCCCTCTTGCT

TCATTATGCTGAATGTCAGTGTATTACTTAAGTTGTTCCTTTCAGCAGAGTTGACTGTTTCTGCCCAG

AAAACCGGCCCTGGGCCAGGAAAATCTGGGCTTCCACACTGGGATGAAAGGTCTGGACGCCCGGATTC

GCATATGCAAAGCGTGGGGGCGTGGCCCCGGGCTCCGGGCCAGGCAGGCTCCGCCCCCTTCCCACC
custom-character

ATGGACTGTTACCGGACCTCACTCTCTAGCAGTTGGATC

TACCCCACAGTCATCTTGTGCCTCTTTGGATTTTTCTCCATGATGCGGCCAAGCGAGCCGTTCCTTAT

ACCATACCTTAGCGGACCCGACAAAAACCTTACGAGCGCGGAAATTACGAACGAGATCTTCCCGGTAT

GGACCTACAGTTATCTTGTGCTTTTGTTGCCTGTCTTTGTCCTGACTGATTACGTTCGGTACAAGCCA

GTTATAATACTGCAGGGGATTTCCTTCATCATTACCTGGTTGTTGCTGCTCTTTGGACAGGGCGTAAA

AACTATGCAAGTAGTAGAGTTTTTCTACGGCATGGTTACCGCCGCAGAAGTGGCCTACTATGCCTACA

TCTACAGTGTGGTAAGCCCAGAGCATTACCAAAGAGTGAGTGGATATTGTAGATCAGTTACCCTTGCC

GCCTACACCGCGGGTTCCGTCTTGGCGCAGCTCCTGGTCTCACTTGCCAATATGTCCTACTTCTATCT

TAACGTTATTAGCCTCGCCTCCGTTAGCGTCGCCTTTTTGTTTTCCTTGTTTCTGCCAATGCCGAAAA

AAAGTATGTTTTTTCACGCAAAACCAAGTAGGGAGATCAAGAAGAGCAGCTCTGTTAATCCCGTTCTG

GAAGAGACACACGAGGGAGAGGCTCCAGGCTGCGAAGAACAGAAACCTACCAGCGAGATACTGTCTAC

ATCAGGAAAGTTGAACAAGGGACAGTTGAACTCACTCAAGCCAAGTAACGTCACAGTTGATGTGTTTG

TGCAATGGTTCCAGGATCTCAAAGAATGTTACAGTTCAAAAAGACTTTTTTACTGGAGCTTGTGGTGG

GCATTCGCAACCGCCGGTTTCAATCAAGTGCTTAACTATGTTCAAATCCTTTGGGATTACAAAGCCCC

AAGTCAGGACTCATCCATCTATAACGGCGCAGTCGAGGCGATTGCTACATTCGGAGGCGCTGTTGCAG

CGTTCGCCGTGGGCTACGTCAAGGTCAACTGGGATTTGCTGGGTGAGCTGGCTCTCGTGGTATTCTCC

GTCGTGAACGCAGGATCTCTTTTCTTGATGCACTACACTGCAAACATCTGGGCGTGCTACGCCGGGTA

CCTTATCTTTAAATCCAGTTACATGCTTCTCATCACTATCGCGGTTTTCCAGATTGCGGTAAATCTCA

ATGTCGAACGATACGCGCTCGTATTCGGCATAAATACTTTCATAGCGTTGGTTATTCAGACAATAATG

ACGGTGATCGTTGTAGATCAAAGAGGGCTGAACCTCCCCGTGTCCATTCAGTTCCTGGTGTATGGTAG

CTACTTCGCTGTTATAGCTGGAATATTCCTTATGCGCTCAATGTACATTACATACAGCACCAAATCCC

AGAAAGATGTGCAGTCTCCGGCTCCGTCTGAAAACCCCGACGTCAGTCATCCGGAGGAGGAGTCTAAC

ATCATAATGTCAACGAAACTTGATTATAAGGATGACGATGATAAATA
custom-character

The PLP1 protein sequence is:

(SEQ ID NO: 56)

MGLLECCARCLVGAPFASLVATGLCFFGVALFCG

CGHEALTGTEKLIETYFSKNYQDYEYLINVIHAE

QYVIYGTASFFFLYGALLLAEGFYTTGAVRQIFG

DYKTTICGKGLSATVTGGQKGRGSRGQHQAHSLE

RVCHCLGKWLGHPDKFVGITYALTVVWLLVFACS

AVPVYIYFNTWTTCQSIAFPSKTSASIGSLCADA

RMYGVLPWNAFPGKVCGSNLLSICKTAEFQMTFH

LFIAAFVGAAATLVSLLTFMIAATYNFAVLKLMG

RGTKFDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PLP1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

PLP1-DNA

(SEQ ID NO: 57)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GGAGTTGGGAACCTTAAGGCACTGGGATGA

GTGAGACACGGTCACCTGGCTGGGTCCCTTTTCTGGCCCTGGGCATAAGAACAAGCATAAGAACAAGG

CGAAGACAGGGAATGTGGAGAGAGAAAAAGGAAACAGAGACAGACACATAGAGAGAAACAGAGACAGA

GACAGGTAACAGAGACAAAGAGATTGAGACTTGGGGAGAGGATAGAATGAATATTAAGGCAATGGAGA

TGGAAGAAAGGAGAAGAGAAATGTGTGTTAAGGGAATGTGGTTGATAAATTGGTATCTGTGGGTTTAT

TGGGAACACATATTTTCTTTCCAGTAGAGTTGCTGTCCCCAGAGCTGCTGCTGAGAACTCAGGGGAAG

CTTTGTGAGAGGGCTCAGTCTGAGTGATGTCCCCTGTGTGGAGAGCTGTCTCATCTATTCGAGCTGTG

AAGGATCATTTGCCTCATCCTCTAAATCTGAACTCCCAAAGTTTGGGCTCACTCCTGCCATCTGATGA

GCTGAGGAGACACATTTGGCGATTTCTTGCTCTTGGTCCTCCCCCTTCTCCAGGGCCATTCCGACAGT

GACCATCCAGAAGTTTATTGCTGGCTCAATCCTACAGTTGAGCTTCCAAAGCAGGCATAGTCTGTGGC

TGGCGAGCAGGGCTGGGGAGGGCGAGGGGCTCTAGGACCCTTTTCCATCAGTCACATGGCCTTAGTCT

CGTCTGCTCTGGAAAGCTACTATTATACCGTTTTGCAAGGGGCAGCATTTCCAGAGATCCTTTTTTCT

TGGGGCTGATACAAGAGCAAAGGATCTAGAGTTCTAGTACTCTAAGCAAGCCTCAAACGGTGCAGGAT

TTGGCCCCAGTGGGCCCACAGGGGCATCTGCCAAAGACTCGTCCATTTCCTAACAGCAGAGCCCAAGC

CAGTAACATGTCCAAAGTCACAGCCCAAAGAGAAAACTGTAAGACACAATCTTGCCTTTCTCCCACCC

CAGGAAGGTACTAGTCTCTGCTCAGTATCTCCCTCCTCTTCTCTCCTCTCCCAAGGCAAAATCACAGG

AAAAGTTCCAGGAGACCATACCTTCCTTCTCCGGAGTCTTCCAACAGGTGCCCCTCTTATTATATGCC

AGCCAGTTGTTTTAAAGGCCATCCATGGGAGGACACCGGCCTCTAGGTCAAGGGAGCTGTGAAGGGAG

ACAGGACTGACAAGGAGCCCAGACAGACACTGTTTAAGATTCACCTGTTCTAGAAAACCTTCCCAGGC

TGATCCCATCTAGCAGTGGGCATTTAAATACCTTCACAGTCTTTAGAAATAGCTTATTGCTAAGGCAG

GTTTTATATAGTATTTCCCTGTTTTTGCTGCTTAGCCATTTTTGTCTTACCGCTTCTTTCTCTGTGGC

AAGGACTATATTTCGTTTCTTCTCTCCACCCTCACTGCCACCTGCTGCTTCACTCTAACCCACTCCCT

GCCTCTTGTCTGCCTGGCTTAAGCTCTCTGATGAAGATATTACACTCTCAGGATAGAATACTGACTAC

CTGATTCCCAGATCGTGTTCTTGACTTGTCTCGAAGTCGATTATCCTTCTTGGAAATCACCCACATCT

TCAACGCTGGCCTTTTCTTTAACCTAGTCTGTGAACTTGCATAGGTCTTGCCCACTTCTGGGTCTTTA

TTATTGTAGCTATAAAATTATTACAATTCTAGCCTCCCCCAGCCTAATCACAATCTGTTCATCGAATT

GACAGCCTGCATTTTGTCTTCATGCAGTTGAAACTGAGAAGGATTTGGAGGAAATTATCTTAAAAGAC

AATTTTTTCTTCTCTATTGTGTTCGTAGAGCTGGGGGTGGGGGTGGGGGAGGAACGCTTATTTTCCAA

GGAATCGGGAGGGGAAAGGTGGAGAGGGCCAAGGGCAGCTAGGAGTGATGTGGGGAGCTGGAGCAGAT

TCGGAAGGACTTTGGGAGCTAATATCTAGGTTTTTGACTCTGAGCCCCTGTTGGGGCTCTCACTTCAT

GGCTTCTCACGCTTGTGCTGCATATCCCACACCAATTAGACCCAAGGATCAGTTGGAAGTTTCCAGGA

CATCTTCATTTTATTTCCACCCTCAATCCACATTTCCAGATGTCTCTGCAGCAAAGCGAAATTCCAGG

CAAGCCTTAGGGAAAAAAGGAAAAACAAAGAAAATGAAACAATTGGCAGTGAAAGGCAGAAAGAGAAG

ATGGAGCCCTTAGAGAAGGGAGTATCCCTGAGTAGGTGGGGAAAAGGGGAGGAGAAGGGAGGAGGAGA

GGAGGAGGAAAGCAGGCCTGTCCCTTTAAGGGGGTTGGCTGTCAATCAGAAAGC
custom-character

TGGGTCTCCTTGAATGCTGTGCTCGATGTCTCGTAGGAGCGCCGTTCGCC

TCTCTCGTCGCCACCGGATTGTGTTTTTTCGGTGTTGCGCTCTTTTGCGGCTGTGGTCACGAAGCTCT

TACAGGTACGGAGAAACTCATTGAGACTTATTTCAGTAAGAATTATCAAGATTATGAGTATCTGATAA

ATGTAATTCATGCATTCCAGTATGTTATTTACGGAACGGCTTCTTTCTTTTTCCTGTATGGAGCCCTT

CTCCTGGCTGAGGGTTTCTATACAACAGGTGCAGTGCGCCAAATCTTTGGCGATTATAAAACTACTAT

ATGTGGAAAGGGGTTGTCCGCGACCGTTACAGGCGGCCAAAAGGGTCGGGGTAGCAGAGGTCAACACC

AGGCACACAGTCTGGAGCGAGTATGCCACTGTCTCGGAAAGTGGTTGGGTCACCCAGATAAATTTGTA

GGGATTACTTACGCTTTGACGGTTGTATGGTTGCTGGTTTTCGCGTGCTCAGCTGTACCCGTTTACAT

CTATTTTAATACCTGGACGACCTGTCAGTCTATAGCGTTCCCAAGTAAGACCTCTGCATCAATCGGTA

GTCTGTGTGCCGACGCGAGGATGTATGGCGTGCTGCCATGGAATGCTTTTCCAGGGAAGGTGTGTGGG

AGCAACCTCCTTAGTATATGTAAAACTGCCGAGTTTCAAATGACGTTTCACTTGTTCATAGCGGCGTT

CGTGGGAGCAGCAGCAACCCTGGTATCTCTCCTCACATTTATGATCGCTGCTACGTACAACTTTGCAG

TACTGAAACTTATGGGACGGGGCACTAAATTCGACTACAAGGACGACGACGATAAATA
custom-character

The TPP1/CLN2 protein sequence is:

(SEQ ID NO: 58)

MGLQACLLGLFALILSGKCSYSPEPDQRRTLPPG

WVSLGRADPEEELSLTFALRQQNVERLSELVQAV

SDPSSPQYGKYLTLENVADLVRPSPLTLHTVQKW

LLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGA

EFHHYVGGPTETHVVRSPHPYQLPQALAPHVDFV

GGLHRFPPTSSLRQRPEPQVTGTVGLHLGVTPSV

IRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDS

DLAQFMRLFGGNFAHQASVARVVGQQGRGRAGIE

ASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQ

WLMLLSNESALPHVHTVSYGDDEDSLSSAYIQRV

NTELMKAAARGLTLLFASGDSGAGCWSVSGRHQF

RPTFPASSPYVTTVGGTSFQEPFLITNEIVDYIS

GGGFSNVFPRPSYQEEAVTKFLSSSPHLPPSSYF

NASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSA

STPVFGGILSLINEHRILSGRPPLGFLNPRLYQQ

HGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDP

VIGWGTPNFPALLKTLLNPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for TPP1/CLN2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

TPP1-DNA

(SEQ ID NO: 59)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
CTCCTTTGGGTTCCACTGACACCCCTGCCC

CTGCCCCTGCCCAGAACCAAGTGCCATTTCTCACTCTGGAGCCTTAATAAACTGCAATTTGTATCCAG

TCTCCAGCTTTGTTCTATAGGGATGACTGGAAGACACCTGGCAGAGTATTGTGGATACCTCAGGAGGC

ACAGAGGGGTGGTGGGGTGGGGATGGCACTGGGAGCTCAGGAGCCTAGCCTGAGGCTGATGATCACAT

CTCTCTGCAGCTATTCTTTTCCCTCTAATATGGGCAAAGAGGCCAGCAGGGCCTTGAGAGGGATCAGT

TGGGTGGGAGAGGGGATCTTGGGGATGAGCAGCTCTGGGCCCGAAGTTCTTAAAATAAGTTGGGGTGG

GTACAAGAGCAGTCAAGTGGTTTATTTGTTCTTCTTGGGGGCCACTAAAAATCCACATTGTAAAAAGA

GCTCAATTTGTTGAGCCTTTGTCATGTCAGGCTCTCTGCAGGTGGCTGCCTTGCTTAATCTCAGTGTA

AATTTTCACAGTCATACAAAGGGATTTGGGAACCACTGGTGTTGCCTGTTCTTTGGGGAGCCAGGCTG

TGAGGGAAAGGCAATTGGCCAGTGTTTGAGAAGTTCATGAGATTGAGGAAATTAGAAAAAAAAAAAAA

AGTTGTGGTCAAAGGGAAATGTTTCTGAGCATGATGCTAGTAAATACAGCTCTAGGATCCACGCTTAG

TGGGAAACTGGAGGGATCAATGGACAGAGAGAAGTCAGATTAATAGGAGTGAGGAAAAACAATGGCTT

GAAAAAACAGAAGGTTATAGTCTAAGAAAGCATTCTATAATTATAATTTCAAAGGTAGAGCAGTTTTG

AGAGATAGCAAGCCCAATGCAGCCATGGGACTGGTTTGCTTAAGTGAAGTGAAGGTAATGCTCACTGG

GTTTAATGAGATGAAGAAATGGAAGGTTAGGGTGTTGAATGGGTCTTTTACCTAGATATTTTGATCAT

CTAGGTCAAATGATCGCAGGAGTTGGGATGGACAGAAAGGTGAAGTGCCATAATCTTCAGTGTGGGAA

TATAATCTATAGGTTAATGGAAGCCAGTGGCCTGTAGGACAACAGCAGGAGTAGAGGGATCTATCTAA

AAAGTATTGAGGTCAGAACAAGGGATTTCACATGAGTATTGGATTAATGGTTTTGGAAGTTAAAATGA

CACTGCTGACACCATCTTCCATATGGATTTTTGGGGGGAAAAAAAGGAAGACTGGAAGGGAATTGAAT

CCTCAGGGTTTTAACTCTCATTGAAAATCCTCTTGTAATGACCCCAGTTGGAAGTAGTAAACTCAGAC

CTCCTTGTGGGCTTTGAGTTACCATTAGAAGAAGCAAAGGTCCGTTTCCATTTTATCCACCTGAGCCC

ACTAAACAAGATGCAAGATTCCTCCATGGCCCTTAGAACAAAGTTGATTTCCTTGAAAACCTTGGGAA

CCCATAATAAACAGGACCCCAGCTGATTGTAGATCTCCTGGGAAGCTACTTAAAACTGGAAACTGATT

TGAATAAAAGGATCCTGGTCTTGCAAAAGCTTTACTCTGTTCATAAATGTAGTCGTAAAATGAAGACA

AAATTGATAATATGGGGACATAAAGGATAAAAGAGGAAAAAAATTTTTTCACTGCAATCTTTCGAGGC

AGATCACTTTTATATAAGTCTCCATATTGTAAATGCAGAAACCTAGGCTCTGAGAGGTTATTTTGCTG

ATGTCATACAGCTAGGAAGAACCCCAGTCTGTGGGTCTCTACAGCCCACTCACTTGTGGTGATTCCCA

GGGGACCAGGCTCAGGACGCAGGTGGGGAGCCCTGGGCTTACTCAGTGCTTGACTGGCCAGAGGGGAG

AATCCGGGTGGCGGCCCCACCCTTGCCTAGCATTTGGGACCACCCATGCAAGGGAGGAGCCAGTACCG

TCACTAGTTACTAGGCAGAGGGGTAGTGGTGGTGGAATATAGAGCTCATGTGATCCGTCACATGAC
custom-character

ATGGGCTTGCAAGCGTGCCTGTTGGGGCTCTTCGCATTG

ATTTTGAGTGGAAAGTGTTCCTACTCACCCGAGCCCGACCAGCGCCGCACACTCCCTCCTGGATGGGT

AAGCCTTGGCCGGGCCGATCCAGAAGAAGAGCTTAGTCTTACTTTTGCATTGCGACAACAGAATGTCG

AAAGGCTTTCCGAACTGGTACAAGCTGTGTCAGATCCGTCTTCACCTCAGTATGGTAAATACTTGACT

CTCGAAAACGTCGCAGATCTCGTACGCCCGTCTCCCCTTACTTTGCATACTGTTCAGAAGTGGCTGCT

TGCGGCTGGTGCTCAAAAGTGCCACTCCGTGATAACTCAAGATTTTCTGACCTGTTGGCTTAGCATCC

GGCAAGCAGAATTGCTCCTGCCCGGAGCGGAGTTCCACCACTATGTCGGTGGTCCTACAGAGACGCAC

GTGGTGAGATCACCTCACCCCTACCAGTTGCCACAAGCGTTGGCCCCTCATGTCGACTTTGTAGGAGG

ACTCCATAGGTTTCCCCCAACTTCAAGTTTGCGCCAGCGGCCAGAACCACAAGTCACTGGTACAGTTG

GACTGCATTTGGGAGTCACCCCCAGCGTCATACGCAAAAGATACAACCTTACTTCACAAGATGTCGGC

TCCGGGACGTCCAATAACTCTCAGGCATGCGCGCAGTTCCTGGAGCAGTACTTTCATGACTCCGATTT

GGCGCAATTTATGAGGCTTTTCGGAGGTAATTTTGCTCACCAAGCCTCTGTAGCAAGGGTCGTTGGTC

AACAAGGACGGGGGCGGGCTGGCATCGAAGCAAGTCTTGATGTACAATACCTGATGTCAGCGGGAGCT

AATATTTCTACGTGGGTTTATAGCTCCCCCGGCCGCCATGAGGGTCAGGAACCGTTTCTTCAATGGCT

GATGTTGTTGAGCAATGAGAGCGCGCTTCCTCATGTCCACACGGTCTCCTACGGAGATGACGAAGATA

GCCTGTCATCCGCATACATACAACGGGTCAACACAGAACTCATGAAAGCCGCGGCCAGGGGCCTCACC

TTGTTGTTTGCTTCTGGAGATAGCGGAGCCGGCTGCTGGTCTGTGTCTGGGCGACATCAATTCAGGCC

AACATTCCCGGCGTCCAGTCCCTATGTCACTACCGTGGGGGGCACCTCCTTTCAAGAGCCGTTCCTCA

TAACCAACGAAATTGTCGACTACATTAGTGGAGGCGGCTTCTCAAATGTGTTCCCCCGGCCGTCATAC

CAGGAGGAGGCAGTTACAAAATTCCTCTCTAGTAGCCCGCATTTGCCTCCATCCAGCTACTTCAATGC

AAGTGGGCGCGCGTATCCCGATGTAGCAGCCCTTTCAGACGGCTATTGGGTAGTCAGTAATCGCGTCC

CCATACCCTGGGTTTCTGGCACTTCCGCCTCAACGCCTGTGTTCGGGGGCATATTGTCACTGATAAAC

GAACACAGGATATTGTCCGGCAGGCCGCCCTTGGGATTTTTGAACCCTAGATTGTATCAACAACACGG

GGCGGGTTTGTTCGACGTAACCCGAGGCTGCCATGAGTCTTGCTTGGACGAAGAGGTAGAAGGTCAAG

GGTTCTGTAGTGGGCCAGGCTGGGACCCTGTAACTGGATGGGGCACCCCGAACTTTCCCGCTCTGCTT

AAAACGCTTCTCAACCCTGACTATAAGGATGACGACGACAAGTA
custom-character

The ACY2/ASPA protein sequence is:

(SEQ ID NO: 60)

MTSCHIAEEHIQKVAIFGGTHGNELTGVFLVKHW

LENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCD

LNRIFDLENLGKKMSEDLPYEVRRAQEINHLFGP

KDSEDSYDIIFDLHNTTSNMGCTLILEDSRNNFL

IQMFHYIKTSLAPLPCYVYLIEHPSLKYATTRSI

AKYPVGIEVGPQPQGVLRADILDQMRKMIKHALD

FIHHFNEGKEFPPCAIEVYKIIEKVDYPRDENGE

IAAIIHPNLQDQDWKPLHPGDPMFLTLDGKTIPL

GGDCTVYPVFVNEAAYYEKKEAFAKTTKLTLNAK

SIRCCLHDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for ACY2/ASPA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

ACY2/ASPA-DNA

(SEQ ID NO: 61)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TTTTTTGGGTCATCCCAAAAATCAAGTACA

CTTTGGGAAACAGGGAGTTAAAAATCTTTCGGAAGTTAACTTGGTATAAGAGTATGAAAAGCCTCTGT

TGCTCTACTTCTGAGGAAATGCTCTCCTTTTTCCTAATAAAGCTTTCCACAGAAGACAAACTCTGTAC

ACAAAAAACAAGGTAAGTATGGGAAATAATTGCTGCAATTCATTAACTCTCAAAAAAGTTATTCATTT

TGACATGTAAGAGAAACTTTATTTATGAATGTGAAATGTGCTTCAAAGTGCTGATCTGTTAAAATTCC

ATAAAACAAGCTTCAAAATGCAAGTCATTTGTGCCAGCTACGAGTAAATAACTGAAGCAGCATTTCCA

GAGAGACTAGGGCAAAGGACAGAACAAACTACAAATCAGCAGAAAAGAAACCAAGCATAGTAGAGTGT

TAATAATTCACCATGGTTACTGCTCTTAAAACCAAAGCAACTAAACAACTGTCATCTGTTTACTTTTA

CGTGTGTTTTCATCATCTCTACACCGTCTGAAGTGTTCAGTGTACATGGATGTGGACAGACAGTCAAA

GCCTACAGGAGCTTTTTTTTTCTATTAGAACAGTCATTTTAATGCATAGATTTGATGTGGTTATTTTG

CTTTCTCTATCTCTGCATTATAAGCTCTTAAAGGAAGAACATTCAGTGGGTTTATTAAATATTAGGAA

GCATTCATATTTTATTTTTCCACCATGTATTTGGTTTGTATGCATGTTTGTTTCCTGAGCACACTGTA

ATGGCTGTTTATGTGAATTCTGAAAGAGCAAAACTAGAACTGTGAAGAAGACCAAAAATAACAGAGAG

GCACCCTATTGTCCTGTGAAAAACACTAGACTTGGGATGAGAAACATGGGTCTCAGGCCTAGGTTCTC

CTACATCCCTGCAGAACCTTAACTGAGTTACTTAACCTCTCTTTCGTTTACCCCTGCAGTGGGGATGT

CAACACCTAACCCACCCTATCGTATAAAATTAATGTATGAATAAACTGAGTGAAAGGACATTATAAAT

TAAACTCTGCAATTGTAATAAATTACTCTTATTGTACCCTCTATCAAACAACCTGGCGTTACTAGTAC

ATGGTATTCCCAGTACTTGAACATATGTGACTTTCTGGGTGACTGAGCATGAAATCAAATCAGATTTG

GCTCAGAGTCATTTCTCCAAAGGGATGTAATCATCTTAGTATTCTGGAAAATTTCCCCTAATAAGACC

CCTTTTTGAGTAACACAGTCCAGTGGAGAGTCCCCGCTGACAGTGAATAAGGCTGTGTCTATGTAAGT

TCACATGATGTGGTTAGCACATGCAGTGTGTCCCAAGACATTTTCAGGCATCACAAAAACTTGAAAAG

TACTAACAGTTGTCTTTCCTTTGGTATTTAGGCAAAAAATGAGGAAGATTCATAAGTAAGTTAACACA

GAATTACCAAAAACCTCATGAGAAAGAAATGAAGGGATGTTTCAGGGTAGCTTTTCGAGTCCCAAGTG

ATCATTGATTTGGCCCTTCTGTTTCTGATTGTGAAAAAGCATTCTGAAAGAATGGGCGCCGGTTCAAG

AGGAGGTCTCTGAGGGTCAGCCTTTGGCTGTTTATAGAGGTGAGATTCAAATGCCCTCAGATCATGAA

AAGTGCTTGAACTCATTTCAGAGAAGAAATGTTTTGAAATGCCCGTGGAAATACTGAGTGGGCCACTT

TTTTATTTTGTGAAATTAGAAACGTATAAACTATTTTTATTATTACAGATAATTGTGAAAGCCTCACT

GGATGACATCCTAGCTGAGGAAAAGAATGGAATTTTTGTATTAGTATGAAATGCTAATTTATTACTGT

ATTTAGATCTACTGACCATCTGAGGGAGTTAGAAGTTAAAGTAAACAGCTGTATCTCTAGTTGATCTT

TGCATATTTTAATCCAAATATGGCAAAGGGCAGGGCTAAAGAAGGGAGTGTCCATAAACGGGGCTC
custom-character

ATGACAAGTTGTCACATAGCTGAGGAACACATCCAGAAG

GTTGCTATTTTTGGCGGCACTCACGGTAACGAACTGACAGGGGTCTTCCTCGTCAAGCACTGGCTTGA

GAATGGGGCTGAAATTCAGCGAACAGGACTTGAAGTAAAACCGTTTATAACGAACCCACGCGCTGTAA

AAAAGTGCACGCGATATATCGATTGCGACCTTAACCGGATATTTGATCTGGAGAATCTTGGGAAGAAA

ATGTCAGAGGACCTCCCTTATGAGGTGAGACGAGCGCAGGAGATTAACCACCTCTTTGGTCCCAAGGA

TTCCGAAGACTCCTACGATATAATTTTCGATCTCCACAACACGACCTCTAACATGGGTTGTACCTTGA

TCCTCGAGGATAGTCGCAACAATTTCTTGATTCAAATGTTCCACTACATAAAAACATCTCTCGCTCCC

CTTCCTTGCTACGTATACCTCATTGAGCATCCAAGTCTTAAGTACGCAACCACCCGGAGCATAGCGAA

GTATCCAGTGGGAATTGAAGTCGGGCCTCAACCCCAGGGAGTTTTGCGGGCGGACATCCTCGACCAGA

TGAGGAAAATGATTAAGCACGCGCTGGACTTCATACACCATTTTAATGAAGGGAAAGAGTTCCCGCCA

TGTGCCATAGAGGTTTATAAGATTATTGAGAAGGTAGATTACCCTAGGGACGAGAATGGGGAAATCGC

TGCCATCATACACCCCAATCTCCAGGACCAAGATTGGAAGCCACTTCATCCCGGCGACCCAATGTTCT

TGACGCTGGACGGCAAAACGATTCCCCTTGGGGGTGATTGCACGGTATATCCAGTGTTTGTGAACGAG

GCTGCTTATTACGAAAAGAAAGAAGCATTCGCCAAAACCACGAAATTGACACTGAATGCAAAATCTAT

CAGATGCTGTCTCCACGACTACAAGGATGACGATGATAAATA
custom-character

The MANBA protein sequence is:

(SEQ ID NO: 62)

MRLHLLLLLALCGAGTTAAELSYSLRGNWSICNG

NGSLELPGAVPGCVHSALFQQGLIQDSYYRFNDL

NYRWVSLDNWTYSKEFKIPFEISKWQKVNLILEG

VDTVSKILFNEVTIGETDNMFNRYSFDITNVVRD

VNSIELRFQSAVLYAAQQSKAHTRYQVPPDCPPL

VQKGECHVNFVRKEQCSFSWDWGPSFPTQGIWKD

VRIEAYNICHLNYFTFSPIYDKSAQEWNLEIEST

FDVVSSKPVGGQVIVAIPKLQTQQTYSIELQPGK

RIVELFVNISKNITVETWWPHGHGNQTGYNMTVL

FELDGGLNIEKSAKVYFRTVELIEEPIKGSPGLS

FYFKINGFPIFLKGSNWIPADSFQDRVTSELLRL

LLQSVVDANMNTLRVWGGGIYEQDEFYELCDELG

IMVWQDFMFACALYPTDQGFLDSVTAEVAYQIKR

LKSHPSIIIWSGNNENEEALMMNWYHISFTDRPI

YIKDYVTLYVKNIRELVLAGDKSRPFITSSPTNG

AETVAEAWVSQNPNSNYFGDVHFYDYISDCWNWK

VFPKARFASEYGYQSWPSFSTLEKVSSTEDWSFN

SKFSLHRQHHEGGNKQMLYQAGLHFKLPQSTDPL

RTFKDTIYLTQVMQAQCVKTETEFYRRSRSEIVD

QQGHTMGALYWQLNDIWQAPSWASLEYGGKWKML

HYFAQNFFAPLLPVGFENENTFYIYGVSDLHSDY

SMTLSVRVHTWSSLEPVCSRVTERFVMKGGEAVC

LYEEPVSELLRRCGNCTRESCVVSFYLSADHELL

SPTNYHFLSSPKEAVGLCKAQITAIISQQGDIFV

FDLETSAVAPFVWLDVGSIPGRFSDNGFLMTEKT

RTILFYPWEPTSKNELEQSFHVTSLTDIYDYKDD

DDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MANBA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

MANBA-DNA

(SEQ ID NO: 63)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
GATTATTCTTTGATGTTCTCTGTTGTCAAA

GTGAAGTAACCTAAATGATGTTATGCTTGCATCCTGGAATGAAAGGAGGAATGAGAATCTTCTATTAT

TGTTTTTCTAAAAATTATATTTCTTAATAAACAGAATATATCCATATGTATCATCAAGGATGAATTTT

CCTCTGATTTGGCTTAATGAAATCTCTGGGAATTATGAAAAAATTCCTTTGCCGCTCTTGTTGCCATA

AACCTTGTGTTATCAGTGTTGCACAGACCATGGCTAGCCATTTAATGCCGTGAATTATGGCATATAAT

TTGAATTGAGAGCTTTGTTTCTATCAAAGGTAAAAATGCTTCTGGAGTGAGTGAGGAAGGCTTTGAAG

CAGTGAGAGCGTTTCCCCTATAGCATCATTGGGCTCTGACAGTAGGACCTTGAAGAGGAGGGTTCTAA

TCCTGTCTGCCACTATGTGACAGGCAAGTCACCTGATCTTTTTTTTTTTTTTTTTTTTAGAGTCTTTC

TCTATAGCCCAGGCTGGAGTGCAGTAGTGCCATCTCGGCTTACTGCAACCTCTGCTTCCTGGGTTCAA

GCGGTTCTCCTGCCTCAGTTTCCCGAGCACCTGCGACTACAGGCACGTGCCACCACGCGCCCAGCTAA

TTTTTGTATTTTTAATAGAGACAGGGTTTCACCATGTTGGCCAGGCTGGCCTCGAACTCCTGACCTCA

AGTGATCCACCCGCCTCGGCCTCCCAGAAGTGCTGGGATTACAGACGTGAGCCACCGCGCCTGGCCCC

GATCTCTTTGAACTCAGTTCCCTCATCTGTAAAGCCAGCGGCTTGGGTTGGATAATCCATACTGTCCT

TTAAGCCAAGATATTCAGGGCTTGTAAATAATGCTGACTTTGCAAAGTAAGATATTGCCCGGTGTCTG

CAGAATCAGGCAATTCCAAGGCCATTGTAAGGCGAAACAAAGCTCAGATTTGATGAGAGAAAATTTCT

TTTCAAGGACTTCTTCCGAAGCATAAATATACGGCAGATAGCGTCAACACAGGAGAAAGGCAGTCTAT

TTTATGCAATGTAAAATTCCGTCTTAACTTCTAGGATTACTGTTACATCCTATTGCAAAAATGGGACT

CAGGTAGACCATTTGACTACAAGACCCGAAATAAGTCAGTGGTATTTCTTGGGTACTCTGGCATTGTT

AGGGACGATCACATATGTTTACTCATTTTATACTTATAACACCTTGAAAACTTCAAGAAACGGAGATG

GAGATTTTGCGGCTTGCCCAGGTCCCACAGCTAGTGAGTGCAGAGGATTTTAAACTCAGCTGCGCGCC

TAGTGCAGGTTCCAGAACCTCAGAAACCTCCGTGGGGCTTTATGAAACATAAGGACGCAGGCCGCTAG

TAACAATAGCTAACGTGAATGCCTTCTCTGGGCCAGGCTCCATGCTGCATGCTATAGTCGCATTTTCT

TGGTTAGCCCTCAGAACAACCTTCTGATGGAGATACTGCTAGTACTTGTTTACTCTTTGAAGGGCGGG

GTAGGCTCTGAGACCCGCGAGTTGAGCTGCAGCGGGGTGAGTGTTACGCTACCAGGTAGACGAGGGTC

TGTGTAAATTTGGCGGAAGGGAAGTGGTGGGTTGTCTCCCAGTTTGGGTTCTCTGAAGGAGTGAGGGG

ACTCTCCAGCTATGGTCTCCACGTACAGTCGGTCTCTGATCTCCCGAGGCTTTGTGCCACTGCGCGCC

CAGGGATCTTTCTGTCCCAATTACCGTGCAAGATTCTTGCCTCCAGTTGTATGTACTGAGGCGGCGGG

AAGAAGCGCCGAGGGAAGGCTCAGACCGCAATGCCCCCCAGCCTGTAGCTATTCTCGGGGGCTGCAGC

TCCCGCACCCGCGACGCCCGGCTTTCAGCGGGTGCAGGCGCAGCCTCCTCGTTCCCCTCCCGCCCGCG

GCTGCGCCCGGAGAGCGCTCAGCTGACCTAGGGGCGGGGCCGGGGCGGGGACCTAAAGCCTCGGCTAC

TTCCGAGGGGG
custom-character

ATGAGGCTTCACCTGCTGCTCCTTC

TCGCGTTGTGTGGCGCGGGTACAACCGCCGCGGAATTGAGTTATTCCTTGAGGGGGAATTGGTCCATC

TGCAATGGCAACGGCAGCCTGGAACTTCCGGGCGCTGTACCGGGTTGTGTGCATTCTGCTCTTTTCCA

ACAAGGGCTCATTCAAGATTCATACTACAGATTTAACGACCTTAACTATAGGTGGGTGAGCCTTGATA

ACTGGACATATTCCAAGGAGTTCAAAATCCCTTTCGAAATATCAAAATGGCAAAAGGTTAATCTCATC

CTTGAAGGCGTTGACACCGTTTCTAAAATACTGTTCAACGAGGTGACTATCGGAGAAACCGACAATAT

GTTCAATCGATATTCTTTCGACATTACTAACGTGGTTCGAGACGTAAACAGCATTGAATTGAGGTTTC

AGTCAGCAGTGCTCTATGCCGCCCAGCAAAGCAAAGCCCATACCCGGTATCAGGTACCTCCAGACTGC

CCTCCTCTCGTCCAGAAAGGTGAATGCCATGTCAACTTCGTGAGGAAAGAGCAGTGCAGTTTCTCTTG

GGACTGGGGTCCATCCTTTCCGACCCAGGGCATTTGGAAAGATGTTCGAATTGAGGCCTACAATATTT

GCCATCTCAATTACTTTACCTTCTCCCCGATATACGACAAGTCCGCCCAGGAGTGGAATCTCGAGATA

GAATCCACGTTTGACGTAGTTAGCTCTAAGCCTGTTGGCGGCCAAGTGATCGTAGCCATACCAAAGCT

TCAAACACAACAGACGTACTCAATCGAGCTCCAACCAGGAAAGAGAATAGTGGAACTTTTCGTTAATA

TTAGCAAAAATATAACCGTTGAGACCTGGTGGCCTCACGGCCATGGAAATCAAACGGGTTACAACATG

ACTGTTTTGTTCGAGCTTGACGGGGGCCTGAATATAGAGAAAAGCGCCAAAGTTTACTTCCGGACCGT

AGAACTTATCGAAGAACCGATTAAAGGTTCCCCGGGCCTGAGCTTTTATTTCAAAATAAACGGCTTTC

CTATCTTTCTTAAAGGCTCCAATTGGATACCAGCAGATTCCTTTCAGGATCGAGTAACATCTGAATTG

TTGCGACTGTTGCTGCAATCAGTAGTAGATGCCAATATGAATACGCTGAGAGTCTGGGGAGGCGGGAT

TTACGAACAAGACGAGTTTTACGAACTCTGTGATGAGCTTGGGATTATGGTGTGGCAAGATTTCATGT

TTGCATGCGCACTTTATCCCACTGACCAGGGTTTCTTGGACTCCGTCACTGCGGAGGTAGCATATCAA

ATTAAAAGGTTGAAGAGTCACCCCTCAATTATAATATGGTCCGGAAACAATGAAAATGAAGAGGCTTT

GATGATGAATTGGTATCACATTTCCTTTACCGATCGGCCAATTTATATAAAAGATTACGTGACGCTTT

ACGTGAAGAACATACGGGAGCTTGTGTTGGCTGGAGACAAGTCCAGACCATTCATCACCAGTTCACCT

ACGAATGGGGCGGAAACCGTAGCCGAGGCATGGGTATCACAAAATCCTAATTCCAATTACTTCGGCGA

CGTGCATTTTTATGACTACATAAGTGATTGTTGGAACTGGAAGGTTTTCCCGAAGGCAAGGTTTGCGT

CCGAATATGGCTATCAGAGTTGGCCAAGTTTTTCCACTCTCGAGAAAGTTAGTAGCACTGAAGACTGG

AGCTTCAACTCCAAATTCAGTTTGCATCGGCAGCACCACGAAGGCGGAAATAAGCAAATGCTTTATCA

GGCTGGACTCCACTTTAAACTGCCCCAGTCCACGGACCCGCTCCGAACGTTTAAAGACACTATATACC

TGACGCAAGTCATGCAAGCACAATGTGTTAAGACGGAAACCGAATTTTACAGACGATCTAGGAGTGAG

ATTGTGGATCAACAGGGCCACACGATGGGAGCTCTGTACTGGCAGCTTAATGACATTTGGCAGGCGCC

CTCTTGGGCTAGTTTGGAGTATGGAGGTAAGTGGAAGATGCTTCATTATTTTGCTCAAAACTTCTTCG

CGCCCCTCCTTCCCGTCGGTTTTGAAAACGAAAACACATTTTATATCTATGGGGTCAGCGATCTGCAC

TCCGACTACTCAATGACGCTTAGCGTTCGAGTGCATACCTGGTCAAGTCTCGAGCCCGTCTGCTCTAG

AGTCACGGAACGCTTTGTCATGAAGGGTGGGGAGGCCGTATGCTTGTACGAAGAACCTGTATCCGAGC

TTTTGCGGAGGTGTGGTAATTGTACTCGAGAAAGCTGTGTAGTGAGCTTCTATCTTTCTGCTGACCAC

GAGTTGCTTAGTCCTACCAATTATCATTTTCTGAGTAGCCCCAAGGAAGCGGTTGGCCTGTGCAAGGC

GCAGATTACGGCGATTATTAGCCAACAAGGGGATATCTTTGTGTTCGACCTCGAGACCTCCGCCGTTG

CCCCCTTCGTGTGGCTTGATGTGGGCAGTATCCCGGGAAGATTCTCCGACAACGGATTCCTGATGACA

GAAAAAACTCGCACAATACTTTTTTATCCATGGGAACCGACTTCCAAGAACGAACTTGAGCAATCATT

TCATGTGACGAGCTTGACGGATATATACGATTATAAGGACGATGACGATAAGTA
custom-character

The LIPA protein sequence is:

(SEQ ID NO: 64)

MKMRFLGLVVCLVLWTLHSEGSGGKLTAVDPETN

MNVSEIISYWGFPSEEYLVETEDGYILCLNRIPH

GRKNHSDKGPKPVVFLQHGLLADSSNWVTNLANS

SLGFILADAGFDVWMGNSRGNTWSRKHKTLSVSQ

DEFWAFSYDEMAKYDLPASINFILNKTGQEQVYY

VGHSQGTTIGFIAFSQIPELAKRIKMFFALGPVA

SVAFCTSPMAKLGRLPDHLIKDLFGDKEFLPQSA

FLKWLGTHVCTHVILKELCGNLCFLLCGFNERNL

NMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQ

AFDWGSSAKNYFHYNQSYPPTYNVKDMLVPTAVW

SGGHDWLADVYDVNILLTQITNLVFHESIPEWEH

LDFIWGLDAPWRLYNKIINLMRKYQDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for LIPA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

LIPA-DNA

(SEQ ID NO: 65)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
TGTATCTAAGAAGCAACTAACTTGCTTTTG

ATTTTACCAGCTAATAGGTGGAAGGGACTTGCCTTGTCTCAGGTGAGACTTTGGACTATGGACTTTTG

AGTTAATGCTGAAATGAGTTAAGACTTTGGGGGACTACTGGGAAGGCATGATTGGTTTTGAAATGTGA

GGACATGAGATTTGGGAGTGGCCAAGGGCAGAATGATATGGTTTGGCTGTGTCCCCACCCAAATCTCA

TCTTGAATTATAGCTCCTGTAATTCCCACATGTTGTGGGAGGGACCCGGTGGGAGATAACTGAATCAT

GGGGGCAGTCTAGCCCATACTGTTCTTGTGGTGGTAAATAAGTCTCACAAGGTCTGATGGTTTTATAA

GAGGAAAATCCTTTTACTTGGTTCTTTCTCTCACATGTGCCGCCATGTAAGACAAGCCTTTTGCCTTC

TGCCATGATTGTGAGGCCTCCCCAGTCCTGTGAAACTGTGAGTCAGTTAAACCTTTTTCCTTCATAAA

TTACCCAGTCTTGGGTATGTCTTTATTAGCAGCATGAGAACAGACTAATACACCTTCTAATTAGTCTC

CCTGCTTCTGTAGTTCAGAATGATCTTTCTAAACTAGATTATGCTGCCCTTCTATTGAAAATATTACA

CTGGCTTCTCATCTTACTCAGAAGACACGGTAAGATCTTGACAAGTGGCTCCCAAGGCACCAGACTTC

TAGGACTTCATGTTCTATTACTTTCTACTATGTACATTCTGTTTTAGCCTCAAAGACCTCACCACTCT

GGCTAGGACCCACCAGGAATATTCCTACCACAGGGCCTTTGTACCTGCTATTTTCACCCAGAATGTGC

TTTCTCCAGTATCTAAGGCTGTTAACTACCTCCTTGCCTGTGCTCAGGTGTCACTTCATAAGAGTCCT

TTCCTGATTACCATATACATATCATCCTCCTTATCCCTGTTTTTTTTTTTTTTTGGGGGATGGAGTCT

CACTCTGTTGTCCATGCTGGAGTGCAGTGGCATGATCTCCGCTCACTGCAACCTCCACCTACCTGGTT

CAAGCCATTTTCCTGCCTCAGCCTCCCAAGGAGCTGGGATTAGAGGCACACACCACCACACCCGCTAA

TTTTGTATTTTTAGTAGAGATGGGGTTTCACCAAGTTGGCCAGGCTGGTCCTGAACTCCTGTCCTCAG

GTGATCCGCCCTCCTCAGCTTCCCAAACTGCTGGGATTACAGGCGTGAGCCACTGTGCCCAGCCCCTT

GTTGTTTGTTGTTGTTGTTGTTTGTTTGTTTTTGTTGTTATTTATAGCACTTATCACCACCTCATGTA

TTATATAGTTATTCATGATGTGTCTCTTCCCATCAGAATATATACAAGAGAACAGGAACCTTGTTTGG

TTGGTTTCTATACCTCCACTGTCTTACTAATGCCTGGCATTTAGTAGGTGCTCAATAAAATCTTTGTT

TTAGAAAATGATTAATAAATAATATGTACATATTGAATATTGTTTCCTCTTTTAACAAATCTTTAATA

ATAATAAAAAATTTAAAGCAGCAAGATTGCTTTGCATCAGGCACAATGATAAGCGCTTTAAATGGAGC

CCATGATTCACTTTCATTTATAGAGCCCACATGCTCTCTGTCAGGCGCAGAAGGTGCCAGCCCTGCAG

GAGCTTCGGGGGCGGAGCAGAAGGCCGCCTAAAACAGCCTTTGCTAAGAGAGCATGCGTAGGCGACGC

GCTGGTAGAGCTGTGGACCTGCCAGCCTGCGAGGCGGAGGACGGGCTCCATCTCTTAGAAACGCCTAC

GGCGCATGCTCTATGGGGTCAACTGGGGGGCTGGCAAGCGGCAGCGCTGGTCTGGGGCGGAGTCTCCG

AGGCACTTCCCGGTGGCTGGCTGCTCTGATTGGCTGAACAAATAGTCCGAGGGTGGTGGGCATCCGCC

CTCCCGACAAGGCAGACCAGGCCCCCTGCAGGTCCCCTATCCGCACCCCGGCCCCTGAGAGCTGG
custom-character

ATGAAGATGCGCTTCCTTGGCCTCGTAGTTTGTCTGGTT

CTGTGGACACTGCACAGTGAGGGTAGCGGCGGTAAATTGACGGCTGTAGATCCCGAAACTAATATGAA

TGTTAGTGAAATAATCTCTTACTGGGGATTTCCATCCGAGGAGTATCTTGTAGAAACAGAAGATGGCT

ATATACTTTGTCTCAACCGGATACCACACGGACGGAAAAACCACAGCGATAAGGGGCCAAAGCCGGTG

GTTTTCCTTCAACACGGTCTTCTGGCAGATTCTAGTAATTGGGTTACCAACCTTGCAAACTCTTCACT

TGGATTCATTCTTGCGGATGCTGGATTTGACGTATGGATGGGGAACTCCAGAGGGAATACGTGGTCCA

GAAAACACAAGACATTGTCTGTATCTCAAGATGAGTTCTGGGCATTCAGTTACGACGAAATGGCGAAG

TATGATCTCCCAGCATCCATAAATTTCATCCTGAACAAGACTGGTCAAGAACAAGTATATTACGTCGG

ACACAGTCAAGGCACTACTATTGGCTTTATCGCTTTCTCCCAAATCCCGGAATTGGCGAAAAGAATCA

AGATGTTCTTCGCATTGGGTCCGGTGGCGTCTGTCGCTTTTTGCACCAGCCCCATGGCGAAACTTGGG

AGGTTGCCGGATCATCTCATAAAGGACCTCTTTGGAGATAAAGAGTTTCTTCCTCAAAGCGCATTTCT

TAAGTGGTTGGGAACACATGTCTGCACTCACGTGATCTTGAAAGAACTTTGTGGAAACCTGTGTTTCC

TCCTGTGCGGGTTCAATGAACGAAATCTTAATATGTCCAGGGTGGACGTCTATACCACCCACAGCCCG

GCAGGTACGTCAGTCCAGAATATGTTGCATTGGAGCCAAGCGGTAAAGTTCCAAAAATTCCAGGCATT

TGACTGGGGTTCTTCAGCTAAGAATTACTTCCACTATAATCAGAGCTACCCGCCCACTTATAATGTCA

AGGATATGTTGGTTCCAACTGCAGTTTGGAGCGGCGGGCACGATTGGCTGGCGGATGTGTATGATGTG

AATATCCTTCTCACACAAATTACTAATCTCGTGTTCCACGAGAGCATACCAGAGTGGGAACATTTGGA

TTTTATATGGGGACTGGATGCTCCATGGCGGCTCTACAATAAAATCATCAATCTGATGCGGAAATACC

AAGACTACAAAGACGACGATGATAAGTA
custom-character

The CTNS protein sequence is:

(SEQ ID NO: 66)

MIRNWLTIFILFPLKLVEKCESSVSLTVPPVVKL

ENGSSTNVSLTLRPPLNATLVITFEITFRSKNIT

ILELPDEVVVPPGVTNSSFQVTSQNVGQLTVYLH

GNHSNQTGPRIRFLVIRSSAISIINQVIGWIYFV

AWSISFYPQVIMNWRRKSVIGLSFDFVALNLTGF

VAYSVFNIGLLWVPYIKEQFLLKYPNGVNPVNSN

DVFFSLHAVVLTLIIIVQCCLYERGGQRVSWPAI

GFLVLAWLFAFVTMIVAAVGVTTWLQFLFCFSYI

KLAVTLVKYFPQAYMNFYYKSTEGWSIGNVLLDF

TGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGV

FSIVFDVVFFIQHFCLYRKRPGLQAARTGSGSRL

RQDWAPSLQPKALPQTTSVSASSLKGDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CTNS and the 5′ and 3′ UTR sequences are listed below using the same

CTNS-DNA

(SEQ ID NO: 67)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG

AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA

CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG

TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA

CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT

GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG
AAACTGAGGCACGAAAATCACTTGAACCCG

GGAGGCAGAGGTTTCAGTGAGCAGAGATTGCACCACTGCACTCCAGCCTGGGTGACAGAGCGAGACCC

TGTCTCAAAAAAAAAAAAAAAAAAAAAAGAAGTGCTCTATTTCAGGAGAAACTGGCACTTTCTGAGCC

TACTCTCCCCTAATGCCAGCTCTCCTGCTCACCCCACCAGGGTCAGAGCCAACTTTGCCTCCAATTCA

TAGTCCTTTAAGTAAGAATCCTTTTAATATGCCCTAATGTCCCAACCAAACTAATCTTGAAAGCTTCT

ATGTAGATACAAAGTGCTCCTGAAATCCCTATCCTCAGAAATGCTTCTGAGCCAAATGGGCTCTGAAC

CCTAAACAACCGTGTCCATGTATGTGGCAAGAGCTTGTGAAAAACAAAGCTGGGCCAGGCGCAGTGAC

TCACAACTGTAATCCTAGCACTTTGGGAGGCTGAAGTGGGCAGATCACTTGAGGTCAGGAGTTCAAGA

CCAGTCTGGCGAACATGGCGAAACCCTGTCTCTACTAAAAATACAAAAAGTAGCCGGGCGCGGTGGCT

CACACCTGTAGTCCCAGCTACTCGGGAGGCTGAAGCAGGAGAATCACTTGAATCCAGTTGGCGGAGGT

TGCAGTGAGCCCAGATCACGCCACTGTACTCCAGCCTGGGCAACAGAGCGAGACTTGGTAAGAAAGAG

AAAGAAAGGAAAGAATGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAG

GGAAGGAAGGGAAGGAGTCTCGCTCTGTCACCCAGGCTGGAGTGCAACGGAGCGATCTCGACTCACTG

CAAGCTCCGCCTCCCGGGTTCGCGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCG

CCCGCCACCACGCCCCGCTAATTTTTTGTATTTTTAGTACAGACGGGGTTTCACCGTGTTAGCCAGGA

TGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGCGCTGGGATTACAGGCGTG

AGCCACCGCGCCCGGCTGACCAAAGGTTTCTTGGTCCGCATTCTGCTTCTGTGGAATGAGCCAGGAGC

CAGTTAGGCCTGATTTGACATCTGATTTCCGGAGGAAAACCCAGACTCTGCCCTGGGCAACAAACTGA

ATCCTGAACTTGAGGTCACAGGGCAGGTGTGAGGAGCGGAGAGCAGCAAGAGTGAAAGGGAGGCCTGT

GGTCATTCCATACACACAAGAGATCAGTTCCTCCAAGGTCAGGGGACAGAGAGCACAGGGATCCAGCG

CCAAGCGCAAGGCCCCCAGAAGAAGCCAGAGAGTCGGGGAGGGGGCGGGGGGGAATCGGTCCCAGCAG

GTGGGAAGGATTCTGGGACCAGACCTAAGGGATCATGAGCACAGCTGCTGCAGGCAGACGGGCCCCTG

GAGAAGCTGGGGACAAGCTGGAATAGAGACTTCATTGCGGGAAGGGCTGTCAGGGAGGCCTCCTGGGG

TGGAAAAGGGTGGTCAGGAGGCTCCTGGAGGCGGCGCGGCCCCGGGGGTCCAACTCACCTGGGGCCCG

GCCACCGCGCTCTCGACCGCCGCCTCTGCCCGCGCAGCACGGGCACAGCTCGCCAGCACTGCGAACCC

GGATGGGTCGTCGGGCGCGGCCCTCAGCAGAGCTGCCTTCACAGATGTGGTGCCCAGGTCAATGCCGA

GGGTGATCGGCCGCGCAGCCATTATCTCCCTGACCCGCGCAGCTCCAGTCTGCAGCCAGCGGCCCCAC

AAGTCCGCGCTCTTCGCCCAGGGGGGCGGGGCAGGGGCGGGGAGTCGCCTGCCAATCTTTCAGCCACA

CCCAACATGGAGGCTTCTCGTCTTCCCACTGGCCGGGGAAGGCGAGCTTCCACGCAACCTCTCGGCGG

GCCCCGGCTATAGGCGGAGAGGCGGCGGAAGGCGGGACCTAAAGGGGGCCCCGCCCCACGGGCTC
custom-character

ATGATCCGAAACTGGCTGACCATATTCATCCTTTTTCCC

CTCAAACTTGTCGAAAAATGCGAGTCTAGCGTCAGCCTCACAGTCCCTCCGGTCGTGAAACTCGAAAA

TGGCTCCAGCACCAATGTGAGTCTGACGCTTAGGCCCCCCTTGAACGCTACCCTCGTTATTACGTTTG

AGATTACTTTTAGGTCTAAAAATATCACTATACTGGAACTGCCTGATGAAGTGGTTGTGCCTCCTGGC

GTCACCAATTCAAGTTTCCAGGTTACCTCACAAAACGTAGGGCAACTTACAGTCTACTTGCATGGAAA

CCATAGCAATCAGACTGGGCCGCGCATCCGCTTCCTCGTTATTCGAAGTTCAGCGATATCAATTATCA

ATCAAGTGATAGGATGGATATACTTTGTCGCCTGGAGTATTAGCTTTTATCCCCAGGTAATTATGAAT

TGGAGAAGAAAATCTGTTATAGGGTTGTCATTTGACTTCGTGGCACTCAATCTTACGGGCTTTGTGGC

ATATTCCGTATTTAACATAGGACTCCTTTGGGTGCCGTATATCAAAGAGCAATTTCTTCTCAAGTACC

CCAATGGGGTAAATCCAGTGAACTCTAATGACGTCTTTTTCTCTTTGCATGCGGTCGTGCTTACACTG

ATCATAATCGTACAGTGCTGCCTTTATGAGCGGGGAGGCCAGAGGGTATCATGGCCTGCAATCGGTTT

TTTGGTCCTTGCCTGGCTTTTCGCTTTCGTTACTATGATCGTTGCGGCAGTGGGCGTAACAACATGGC

TTCAATTTCTCTTTTGTTTTTCTTATATAAAGCTGGCAGTCACTCTGGTCAAGTATTTTCCCCAAGCA

TACATGAACTTTTATTACAAGTCTACTGAGGGGTGGTCCATTGGGAACGTCCTCCTTGATTTTACAGG

TGGCTCCTTCAGTTTGTTGCAAATGTTTCTCCAAAGCTATAATAATGACCAGTGGACATTGATATTTG

GCGACCCGACTAAATTCGGGCTCGGTGTATTCTCTATCGTTTTCGACGTTGTATTCTTTATACAGCAC

TTCTGTCTCTATAGAAAACGCCCTGGTCTTCAGGCTGCCAGAACCGGTAGCGGTTCTCGGCTGAGACA

AGATTGGGCGCCATCTTTGCAACCCAAGGCGTTGCCACAAACAACTTCTGTAAGCGCATCCTCTTTGA

AGGGAGACTATAAAGATGATGACGATAAGTA
custom-character

The GNS protein sequence is:

(SEQ ID NO: 68)

MRLLPLAPGRLRRGSPRHLPSCSPALLLLVLGGC

LGVFGVAAGTRRPNVVLLLTDDQDEVLGGMTPLK

KTKALIGEMGMTFSSAYVPSALCCPSRASILTGK

YPHNHHVVNNTLEGNCSSKSWQKIQEPNTFPAIL

RSMCGYQTFFAGKYLNEYGAPDAGGLEHVPLGWS

YWYALEKNSKYYNYTLSINGKARKHGENYSVDYL

TDVLANVSLDFLDYKSNFEPFFMMIATPAPHSPW

TAAPQYQKAFQNVFAPRNKNFNIHGTNKHWLIRQ

AKTPMTNSSIQFLDNAFRKRWQTLLSVDDLVEKL

VKRLEFTGELNNTYIFYTSDNGYHTGQFSLPIDK

RQLYEFDIKVPLLVRGPGIKPNQTSKMLVANIDL

GPTILDIAGYDLNKTQMDGMSLLPILRGASNLTW

RSDVLVEYQGEGRNVTDPTCPSLSPGVSQCFPDC

VCEDAYNNTYACVRTMSALWNLQYCEFDDQEVFV

EVYNLTADPDQITNIAKTIDPELLGKMNYRLMML

QSCSGPTCRTPGVFDPGYRFDPRLMFSNRGSVRT

RRFSKHLLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GNS and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GNS-DNA

(SEQ ID NO: 69)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

TCTTGCCTAGGCTAGATTGCAGTGGTGCAGTCATA

GCTCACTGCAGCCTCGAACTTCTGGGCACAAACAA

TCCTCCCACCTCAGCCTCTTAAGTAGCTGGGACTA

CGGGCATGCACTACCATGCCCAGCTAATTTTTATA

TTTTTTGTAGAGCCAGGGTCTTGCTGTGTTGCCCA

GACTGGTCTCAAACTCCTGGCCTCAAGCAGTCCTC

CTGCCTCTGCCTTCTAAAGTGCTGGGATAACAGGT

GTGAGCCACTGCACCGGGCCTAAAGTCTAAATTCC

TATGTGGCCCTGCATCACTGACTCCTGCCTGCCTC

TCTGACCTCATCTTACCTCACTCTCCCTTTTCCTC

CCTAAGCTGCTTCCATCACCACACTGGCTTCTCTG

TTTCCTCCCAGGTGCCTCTCTCCTTCCTCTGGCAG

CCCTTGTACTTGCTATATACCCAGCCTGAAACATC

TTCTGAATTTTTGCATGACTGACTCCTCATCGCAT

GGCTCTCCGTACTGAAGTTACCTCCTGAGAGGCCT

TTTCTGACCACCCATCTAAAGTAGTTCCCCTTTCT

TCCCACCAGCTGTAATCACATCATCCTGGTTTATT

CTCTTCATAGCACTTACCACCACCTGAAATGACTG

ATTGTTTACCTGTTAGTTGTTTTAAGTCCCCAAGA

GTGCAGAGATCATGAGGGCGAGGACCATCTATCCT

CTGTCCACCACTGCCTAGATTAATGCCTGGCACGT

GTTGTGTTTAATAAATGTTATTACACAGTCTTACT

GTAAATCAGATATTCTTTCATAATTTTACATATTT

ATCAGACAGTTTGACAATTAAGTCCCATACAGTCA

ACTCTGGTCCTTTTCTCCACTTACTCTTTGAATCC

TCATTTCACCTTCAAATGTCCTCACAGTAACTCAG

GTGTTTTATCAAACCAATGTCTCATGAAGCCCAGT

ATTCTTTTCCTGAGGATGGTACCCAGTGATGCTTT

GAGGAGAGTATGGCTGACGACCTTGCTTCGGAAGG

CTGGCGAAGATCTTCTGCTTCTCTAGCGTCTCTTG

GCAGCCTCTTCTGGATCTACTCATGAAATTATCAG

AGCTTTTTTTGGATAAGTTAGAATCCTCATCCTTT

TGAGTTTATGGATTCCGTAGGTTTTGTATTTATAT

AAAACAATGGGGAAAAGTCATTTATACATTATTGA

AAATGAGGCTCCTGTTAACCTACTTATGTATTTAG

ATTAGCAATCTTTAAGGAATTATTGCACAACAAAA

TATACTTAAAACTGCATTCAATATGGTCTTAGGTT

TCAAAGGTATCTCAGAATCATCGTGAACTGACCCA

TATTACAACTAAAATGACCTCTTCAATGGTGCTTT

TTGCTGTCTGGAATCTGAAGAATATTAGTGTTCCT

TTTATTCGTATTTAAATGACTGTCTTCATACTTTT

GTCCTCATTCTAGAAGGAAGTTAATTGTTCTCTGT

ACTTGTAAGGATCTTAGATTTTGAACAAAAGATGA

AAAGCAGGACATAAAATAGTTTCTGAGTAGCCTTT

TGCCTGACAGTGTTCTGTGTACACCTGCTTGCCAC

CTGGTTCAAGTCCTTATCCTGAGGTGCTTGTGGGT

CTATGCAGACAACAGTAGTTGGTAGTTGAACAGTG

TGTGTCTGGCCTCCACCACTGAGTGTGTGAGGTTT

GAATCAGTCTCGGAGTCCTGGGGCCTTGTCTGGCT

TTCAGAATCCAACTGTTGTCTTACTTCTGTTCTAT

AGGGCGGAAGGCTCCCTTTATATCATTTCCCACAT

CCTACTTCTAAAGATTAATTCATGGAGATAGGTCT

GCCCTATCTGCCTTATCTGGGCGCTGATGACTAAT

AAGGGCACAAAGATGTTATTGCCATCAACTGAACT

TTCCCTTCCTGCAAGCATTTTGACTTCCTGCACTT

TTATACAGGATGGAGCTGGCCGGAACCAAACTTGT

CTCTAGAATCATACAAGACTCTCTTTGGCTGTTGC

TTAGAGCTGACCATTTGGGAATAAAAGATTGAGTA

AGATGTAACAAAACAGGAATTCTGGGCTGTGTGTC

TCAATTTATTGGAAGAAATTGTTTAATGGATAATT

ACTTACTTTTAC

custom-character

ATGAGGCTCCTGCCGCTCGCCCCGGGACGGCTCAG

AAGAGGGTCTCCAAGGCACCTCCCAAGTTGTTCCC

CCGCGCTTCTCTTGCTTGTGCTGGGAGGATGTCTC

GGAGTTTTTGGCGTTGCGGCGGGAACACGACGGCC

AAACGTTGTCCTCCTCTTGACGGATGATCAAGACG

AGGTGCTGGGGGGTATGACACCGTTGAAGAAGACC

AAAGCACTGATAGGTGAGATGGGTATGACTTTCAG

CAGCGCTTATGTTCCGTCTGCCCTTTGCTGCCCTA

GCCGCGCCAGTATCCTTACGGGGAAGTACCCACAT

AATCACCATGTAGTTAACAACACCTTGGAAGGTAA

TTGCTCTTCAAAGTCCTGGCAGAAAATTCAGGAAC

CCAATACCTTCCCGGCCATACTTCGATCTATGTGT

GGATATCAAACATTTTTCGCCGGGAAGTATCTCAA

TGAATACGGTGCTCCCGATGCGGGCGGACTCGAAC

ACGTTCCCCTGGGTTGGAGCTATTGGTACGCACTC

GAGAAAAATTCAAAGTACTATAATTACACCTTGTC

TATAAACGGAAAAGCCCGGAAACATGGTGAGAACT

ATTCTGTCGACTATCTGACGGACGTGCTGGCGAAT

GTAAGCCTCGATTTTCTTGATTACAAGAGCAATTT

CGAACCTTTCTTTATGATGATCGCAACGCCTGCTC

CCCATAGTCCATGGACTGCGGCACCACAATATCAA

AAAGCGTTTCAGAATGTCTTTGCCCCACGAAACAA

AAACTTTAATATACACGGCACCAATAAGCATTGGC

TGATAAGACAAGCGAAGACACCCATGACCAATTCA

AGCATACAGTTCCTGGACAACGCATTCCGCAAGAG

GTGGCAAACGCTGCTCTCAGTTGACGATTTGGTTG

AGAAATTGGTAAAAAGACTTGAATTTACTGGCGAA

CTGAACAATACGTATATCTTCTATACATCTGATAA

CGGATACCACACTGGTCAGTTTAGTCTCCCCATAG

ATAAACGGCAGCTCTACGAGTTCGATATCAAAGTA

CCCTTGTTGGTAAGGGGACCGGGAATAAAACCTAA

CCAGACGTCCAAAATGCTGGTGGCAAACATCGACC

TCGGCCCAACGATTCTGGACATCGCTGGGTATGAC

CTTAACAAGACACAAATGGATGGCATGTCCCTGCT

GCCAATCCTCAGAGGGGCCAGCAATCTTACATGGC

GCTCAGATGTCCTGGTAGAATATCAAGGTGAGGGA

CGGAATGTAACAGACCCTACCTGTCCCAGCTTGAG

CCCTGGTGTATCTCAGTGTTTTCCTGATTGTGTTT

GTGAAGACGCATACAATAACACATACGCTTGTGTA

AGGACGATGAGTGCACTTTGGAACTTGCAGTATTG

CGAGTTTGACGATCAGGAGGTGTTTGTTGAGGTGT

ATAACTTGACGGCAGATCCGGACCAAATTACCAAT

ATAGCTAAAACCATTGATCCGGAACTCCTCGGCAA

GATGAATTATAGACTTATGATGCTGCAGTCATGCA

GTGGTCCCACATGCCGAACGCCAGGAGTGTTCGAC

CCTGGGTACCGGTTCGATCCCCGCCTGATGTTCTC

CAATAGGGGTTCAGTTCGGACGAGGAGATTCTCAA

AGCACCTCCTTGACTATAAAGATGACGACGACAAG

TA

custom-character

The HGSNAT protein sequence is:

(SEQ ID NO: 70)

MSGAGRALAALLLAASVLSAALLAPGGSSGRDAQAAPPRDLDKKRHAELK

MDQALLLIHNELLWTNLTVYWKSECCYHCLFQVLVNVPQSPKAGKPSAAA

ASVSTQHGSILQLNDTLEEKEVCRLEYRFGEFGNYSLLVKNIHNGVSEIA

CDLAVNEDPVDSNLPVSIAFLIGLAVIIVISFLRLLLSLDDFNNWISKAI

SSRETDRLINSELGSPSRTDPLDGDVQPATWRLSALPPRLRSVDTFRGIA

LILMVFVNYGGGKYWYFKHASWNGLTVADLVFPWFVFIMGSSIFLSMTSI

LQRGCSKFRLLGKIAWRSFLLICIGIIIVNPNYCLGPLSWDKVRIPGVLQ

RLGVTYFVVAVLELLFAKPVPEHCASERSCLSLRDITSSWPQWLLILVLE

GLWLGLTFLLPVPGCPTGYLGPGGIGDFGKYPNCTGGAAGYIDRLLLGDD

HLYQHPSSAVLYHTEVAYDPEGILGTINSIVMAFLGVQAGKILLYYKART

KDILIRFTAWCCILGLISVALTKVSENEGFIPVNKNLWSLSYVTTLSSFA

FFILLVLYPVVDVKGLWTGTPFFYPGMNSILVYVGHEVFENYFPFQWKLK

DNQSHKEHLTQNIVATALWVLIAYILYRKKIFWKIDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HGSNAT and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HGSNAT-DNA

(SEQ ID NO: 71)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

CAAAAGGGTAAAGTTGTTTACCATTCGGACTTTTG

GCCCCCTTCTCCGTGTACAAATTGGTAAAAAGCCT

CAGGATTTTTGAGCTGTCCTTATCCCTCCCCTTGT

TTCTTTTCTTTTCTTTTTTTTTTTGAGACAGGGTC

TCACTCTGTCGCCCAGGCTGGAGTGCAGTGATGTG

GTCTTGGCTCACTGCAACCTCCGTTCAAACGATTC

TCCTGCCTCAACCTCCTAAGTAGCTGGGAGTACAG

GCAGGCACCACCACTGCTGGCTAATTTTTGTATTT

TTAGTAGAGACAGGGTTTCACCATGTTGGCCAGGC

TGGTCTTGAACTCCTGACCTGCCAGGCTGGAGTGC

AGTGGCATAATCTTGGCTCACTGCAAACTCTGCCT

CCCGGATTCAAGTGATTCTCCTGCCTCAGCCTCCC

AAGTAGCTGGGACTACAGGTACTTGCCATGACGCC

CGGCTAATTTTTTGTATTTTTAGTAGTGACAGGGT

TTCACCATGTTGGCCAGGATGGTCTCGATTTCTTG

ACCTCGTGATCCACCTGCCTTGGCCTCCCAAAGTG

CTGGGATTACAGGCGTGAGCCACTGTGCCCGGCCA

TATGTGTTTAATAACCCAGTTTGTCTCTTCTTGCC

TTCAGGACATCAAACGGTCATGCTACTGGAAGCTC

GGACCATGGCCCCTTCTGCTGGGCACCCTTAGATA

GGCCTCTGAGGGAGATCTGATTGCCATTTTCCCGA

AACAGTGCCCCCTATCAGCAGGAAGCAGTTAAGAT

CTGTCTTTGTCCCTATTCTTATCCTAGTGGCAGTT

AGATAGACTTCTTTAGAGCGAGGAATGAGCCAGAT

GGGAAGGGTTCCCTGGTAAAACTCCAACTGGCCTG

TGCACTGCTCTGGGGTGGAGCCACAGAAGTTCGCT

CCTCAGTTTGCAGCTGGGAGGAGCCTGGCCCTCCT

CTTCCTCGGGAGAACCTGGGATTTAATCTGTGAGG

TGGGAAGCCTACAACTAGGAGAACTCTGGCTCTGC

TGAGTCCCTGTTCCCCTTTTTCTTCCTTTACACCC

AATAAAACCCTGCCTTACCCTTCAAATTGTCTGCG

AGCCTAATCTTTCCTGGCGTGTGACAAGGACCTCC

ACCGTCTTTAGCTGAACTAAGGAAAAGTCCCGCAA

CATTTTCATGTGTGCCTTTGTATTTTTATTACATA

TATGGATGTCCCTAAACAACATACATTATTGTTTT

GCTTTATATATTAAAAAGGCATTCTGCAATTTGCA

TTTTCCCCAGCCTTGTGTTTTGAGATTTATCCATG

TGGATGCGGGAAGCTGTAGAGCACTTCCCCTGCTG

TGGGGCAGTTTGTTTTCTCGCTGGCGGACATTCAG

CTTGTTGACAAGGTTTTGCAATTACAAGCACCTCT

GCTATAGGTATTACTGTACCTGTCCCTTATACCTG

CGATAGTGTCTCCCGGCATACAGCCAAGAATGGGT

GTGCACACTCCTCGACCTGCTCCCTTCCACTTCGT

CAGCCTGGCCGGGGGCTCTTTCAAGAGGTGGGGCC

GCTTGGTGGCTTCTAAGTCGTGCCTCTCCCTCTGG

GTAATAAACGCCTTGGGGGCAGGGACTTTGCAGTC

TTGCTTATTGAGGCGTTTTCCAAAACAGGGACCGA

GGGCTCTAACACCCGTGCGGAGGGTGGCCGGCGGG

GGCGGGAGTTTGGCAGAATGCGGCTGGAGAAGGTG

GGGCGAGGGAAGAAGGCTCCTGGCCTGCAGGGGCC

TCTCTTCCGGCTGTTTTTCCTCCCGAAGACAAACA

CTCCCAACGCAGGGGCGCAGAGCCTCGGCTTCTTT

CCTGGCCAGCTCCCTCAAGGCAGGGCCTAGCATGG

CCCGGCCCAGCCCCTAGGTTCCCCCGCCCGCGGCT

CCCGGGCGCCTCCGCCTCCCGCGGTGACTCAGGCG

GCGGTGACGGCAGCGGAGGGGGCGATGACGGGCGC

GCGGGCGTCCGCGGCGGAGCAGCGCAGGGCGGGGC

GCAG

custom-character

ATGAGCGGCGCGGGCAGAGCTTTGGCGGCCCTTCT

TCTGGCGGCATCTGTGCTTAGTGCAGCACTCTTGG

CTCCTGGGGGAAGTAGTGGTCGAGACGCTCAGGCC

GCGCCACCGAGAGATCTGGATAAGAAACGGCACGC

AGAGCTCAAGATGGACCAGGCACTTCTGCTCATAC

ACAACGAATTGCTTTGGACCAATTTGACGGTATAT

TGGAAGAGTGAGTGTTGTTACCATTGTCTCTTCCA

GGTTCTTGTGAACGTGCCACAGAGTCCTAAAGCTG

GGAAGCCTAGTGCTGCGGCGGCATCTGTTTCTACA

CAGCATGGTAGCATACTGCAACTTAACGACACTCT

GGAGGAAAAAGAGGTATGTCGATTGGAATATAGAT

TTGGCGAGTTTGGCAATTATTCATTGCTGGTTAAA

AATATCCACAACGGTGTTAGCGAGATTGCATGCGA

TCTCGCTGTTAATGAAGATCCGGTCGATTCTAACC

TGCCGGTCTCAATAGCTTTTCTGATAGGGCTGGCA

GTGATTATCGTAATCTCATTCTTGAGGTTGCTCCT

CTCACTCGACGATTTTAACAACTGGATCAGCAAGG

CAATTAGTTCCAGAGAAACTGACAGGCTCATTAAC

AGCGAACTTGGTTCACCCAGTCGCACAGACCCCCT

TGACGGCGATGTGCAACCTGCGACATGGAGATTGT

CCGCCCTCCCTCCGCGACTGCGATCAGTGGATACC

TTCAGAGGAATTGCGCTCATTCTTATGGTTTTCGT

AAATTACGGAGGGGGTAAATACTGGTATTTTAAAC

ATGCCAGTTGGAATGGACTCACCGTTGCAGATCTC

GTGTTCCCGTGGTTCGTCTTCATTATGGGCTCATC

CATTTTTCTCAGCATGACCTCCATCCTCCAGCGAG

GATGCTCCAAATTTCGCCTCCTCGGAAAGATAGCC

TGGCGAAGTTTCCTGTTGATTTGTATTGGGATTAT

TATCGTAAACCCCAACTACTGTCTGGGGCCTTTGT

CATGGGATAAAGTAAGGATACCTGGAGTTCTCCAA

AGACTCGGCGTGACTTATTTCGTCGTTGCAGTTCT

CGAACTCCTCTTTGCCAAGCCGGTCCCCGAGCACT

GCGCATCAGAACGCTCATGCCTCAGCCTTCGCGAC

ATAACAAGCAGTTGGCCTCAGTGGCTGCTTATCCT

TGTCCTGGAAGGCCTTTGGCTTGGTCTTACCTTTT

TGCTTCCCGTACCAGGATGCCCAACTGGCTACCTC

GGGCCCGGAGGGATCGGCGACTTTGGAAAGTATCC

CAATTGTACCGGAGGAGCCGCGGGCTATATTGATC

GACTTCTCTTGGGGGATGACCATCTTTACCAACAC

CCGTCTAGTGCAGTACTTTACCATACCGAGGTAGC

CTATGACCCGGAGGGAATCCTTGGTACCATTAACT

CAATAGTCATGGCGTTCCTTGGTGTACAGGCTGGA

AAAATTCTCCTTTACTACAAAGCTCGAACGAAGGA

TATTCTTATAAGATTTACAGCGTGGTGCTGCATCC

TTGGACTGATTTCTGTGGCCCTGACGAAGGTATCC

GAGAACGAGGGATTCATCCCCGTTAATAAGAATCT

GTGGAGCCTTTCCTATGTCACCACGCTCAGCTCTT

TTGCTTTCTTCATTTTGCTTGTTCTCTATCCAGTA

GTGGATGTAAAGGGCCTGTGGACAGGGACTCCGTT

CTTCTACCCGGGGATGAACAGCATACTTGTTTATG

TGGGACATGAAGTATTTGAAAACTATTTCCCCTTT

CAATGGAAACTTAAAGATAATCAAAGTCACAAAGA

GCACTTGACACAAAACATTGTAGCGACAGCGTTGT

GGGTCCTCATTGCATATATCCTCTACAGAAAGAAG

ATATTTTGGAAGATAGACTATAAAGATGATGATGA

TAAGTA

custom-character

The NeuroD1 protein sequence is:

(SEQ ID NO: 72)

MTKSYSESGLMGEPQPQGPPSWTDECLSSQDEEHEADKKEDDLETMNAEE

DSLRNGGEEEDEDEDLEEEEEEEEEDDDQKPKRRGPKKKKMTKARLERFK

LRRMKANARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYI

WALSEILRSGKSPDLVSFVQTLCKGLSQPTTNLVAGCLQLNPRTFLPEQN

QDMPPHLPTASASFPVHPYSYQSPGLPSPPYGTMDSSHVFHVKPPPHAYS

AALEPFFESPLTDCTSPSFDGPLSPPLSINGNFSFKHEPSAEFEKNYAFT

MHYPAATLAGAQSHGSIFSGTAAPRCEIPIDNIMSFDSHSHHERVMSAQL

NAIFHDDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NeuroD1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

NeuroD1-DNA

(SEQ ID NO: 73)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

TGTCGCGAACTGGAGGTTTCTGCTTTCTGGGGGTG

AGGACAAGGATTTAGCAGAGGGACCTCTAGGCTAC

CCCTGACCTCGAAGCTAGCTGGAGTCCTTTCTCCC

ACTCCGTCCCCAGTTCTCCTCCGGAACTCCCCAAA

GTTGGAAAAATGAGAGCCTAGGCACGAGTTGCATA

TGCCTGCGGCATAGTGTGCTGCCAGTCGGGGCAGC

TGCCGGGTGAGGGGCAGTACTTAACCTGGCCCTGC

CGCAAACGTCGGGCTGTGTACTATCTTCTAAGGGC

TAGTACTCCGACGCCCTCGAGTTTTAGCCCAACAC

TGAAGATACAGACAGTACAGGGGTAAATCCTGGGC

CCAGGCTCCTGGGTGAATTATTTTATCCTCCCCTA

TGCGCTTTGTCAGCCAAGTGAATGTAGAAAAGCAA

GCAAAACTCCAGAACCCCACAACGATTCACGCCAC

GCTTCGGTGGCACAACTCTTTTCTTCCCCTTTTAG

ATTAGTACTGTGCAGGGAAGGCTGCACCTGCTACC

TTCAGACACCGGGGATCTGGCTAGGACCCTCTTCC

TCTACCCCTACTCTCTCCTCCCGTCCCCACCCTCT

CCCAGATGCACCCCAATCCAGCCTCTCAACCCTGT

CGCTGTTTGCAAACTCGAGGGATGTTTAGTGCAAT

TGCCTTTAAATAAGCAATTCACGTAAGAGGTATTT

ATTGCAGAGGGTTTCAGGTCTGGGAGGGGGTAAGG

AGTTAGTTAATGAAGGATTAGAGGCAAAGCTGGGA

AAGAACGAGTAGACAGGCCAGTTTCTTTCTTTCTT

TTTAAAATCTATTATTCTGGAAAACCCTTGTTCGA

AAAGAGTAAAGAATTGCTATTTGGGCAACAATATG

GCTCCTTCAGAACTGGTCGAGAATTTCTGTGGTCT

TTGCTTGACCTTCAAGTTGGGAGTTTCAAATCAGA

GGCTTTGAAGTCTGGAGGAGTTCGCAGCCATTAAT

CCTTCCGGGGTTGTGCTAAAGGCGTTTCTAGAAAG

AGATCGGAAAGACCCGTTCAGCACAGGCCCATTGC

ATCTTCTCTTTGAAAACGCTTGTCTGAATCAAGTA

TCTTATACAGACCCGAGACTGAGGGGAGCAAGAGC

GCAGGTCCGGCTGTGGCGAGGTGTCCACCACCGTA

CTTGTGGTCAATGCCTGGACTAGAGAGCCGAGGCC

GTCCAGGGCGGGCTGGCCAGGGAACCAGAAGCGTC

CCTGGACTGGCTGAGTGAGGGTGCCCTTTCCAGCA

ACCCAGTGGCCATGGTTAAAAGGCAGAATACAACC

GTCAAAGAAGTCCCCAGCTCCCACATAAGAGAGCG

CAAAGGCCAATGGAACCAAGGCCTCCTCGCGAGAA

CTAGCTCGCTTTGAGGACAAGATCCTGGGGATGGA

GGTGGGGACTGACGTAGTGAGAGGGTCTGGAGGAA

CAGTCGTAGCTGAAGGTCAGGACATGAAGAATTGC

ACGTATGGTAGGGATAGAATGGCAGGTACAACTTT

TCTGTACTGAAGGAACTGGGAGAGGACGATCCGGT

TAGGGAGGTTGGGGAACTAATCTCAACGCTGCGTT

TACAGATGAAGCCGCTTTTATATGGCGTATATGTT

TGCTTAGAGGGGCCGACGGAGATTAGGAGAAGCCA

TCCTTTGGCGCCAATGATCAAAGCGTCTGCCAAGG

AGAAGAAGCCAAGGGATGGGCCTTTCAGAGAGGGC

AAGGAGTCATGCTGCTCTGGATGCCAGTGTCAGGA

CAAGAAATCGAAAGGAGCGAGGACTCTTCACTGCG

TGCCTCAGTCTCCCCGCTTCTGCCTCTTTCACCTC

TGTCCTACTTCCGGCGCGAAAGCAGGCCACTCGCT

CTGATCTAGACCTAGTTAACATTAGCTTTTCCCTT

CCTTCCCTCAAATCCCCTCCCCCCTCTATCCCCGT

CCCTTCTGCCGCCTGAAAGGGTTAATCTCTCCTGC

GGGTAAAAACAGGTCCGCGGAGTCTCTAACTGGCG

ACAGATGGGCCACTTTCTTCTGGCCACAAAGGGGC

CGGAATGGAGCGCTCCGCGGCATACAAATGGGCAG

GTCACGTGGTTCCAGGCTCTTGGCTGGACCGGGAA

GACCATATGGCGCATGCCGGGGAGGAAGGAGGAGG

GGCGGGGGTAGGGGTGGAGGGTGAGGGGAGCGGTT

GTCGGAGGAGGGCGGGAGACGAGCAAGGCGTGGGG

AGAAGTGGGGAGGAGGGGAGAACGGGGAGCGCACA

GCCTGGACGCGTGCGCAGGCGTCAGGCGCATAGAC

CTGCTAGCCCCTCAGCTAGCGGCCCCGCCCGCGCT

TAGCATCACTAACTGGGCTATATAACCTGAGCGCC

CGCGCGGCCACGA

custom-character

ATGACGAAAAGCTACAGCGAGTCAGGGTTGATGGG

GGAGCCTCAACCCCAAGGGCCCCCATCTTGGACGG

ATGAATGCCTGTCATCACAAGACGAGGAACACGAG

GCAGACAAGAAGGAGGACGACCTGGAAACGATGAA

CGCTGAGGAAGACAGCCTCAGGAACGGAGGCGAAG

AAGAAGATGAAGACGAAGACCTGGAGGAAGAGGAG

GAAGAAGAGGAAGAGGATGACGACCAGAAGCCCAA

ACGGCGCGGGCCCAAAAAGAAGAAAATGACTAAAG

CCAGGTTGGAGCGGTTCAAACTCAGGAGGATGAAG

GCTAATGCAAGAGAGAGGAATCGCATGCATGGACT

CAACGCCGCTCTCGATAACCTCCGGAAGGTCGTGC

CATGTTATTCTAAAACACAAAAACTGTCCAAAATC

GAGACCCTGAGGTTGGCAAAGAACTACATATGGGC

GCTCAGCGAGATTCTTAGATCTGGTAAGTCTCCGG

ACCTCGTTTCCTTCGTCCAAACCCTGTGTAAAGGT

CTGTCACAGCCAACCACCAACCTTGTAGCTGGGTG

CTTGCAGTTGAACCCCCGCACTTTCCTTCCTGAAC

AAAATCAGGATATGCCTCCGCACCTCCCTACCGCC

AGTGCATCTTTTCCGGTACATCCCTACTCATACCA

AAGCCCGGGTCTGCCTAGTCCGCCGTATGGTACAA

TGGATTCCTCCCACGTGTTCCACGTAAAACCCCCA

CCTCATGCCTATTCCGCTGCCTTGGAGCCTTTTTT

TGAGTCTCCGTTGACAGACTGCACCAGTCCTTCTT

TTGATGGGCCCCTGTCACCTCCTCTTAGCATCAAT

GGAAACTTCTCTTTCAAACACGAGCCAAGTGCAGA

GTTCGAGAAAAATTATGCTTTTACTATGCACTACC

CCGCAGCTACCCTGGCAGGTGCGCAAAGTCATGGA

TCTATCTTTTCAGGAACGGCTGCGCCGAGGTGTGA

GATACCCATTGATAATATCATGAGTTTCGATAGCC

ACAGCCATCACGAGCGCGTGATGAGCGCTCAACTG

AATGCAATTTTTCATGACGACTATAAAGATGACGA

CGATAAGTA

custom-character

The SLC17A5 protein sequence is:

(SEQ ID NO: 74)

MRSPVRDLARNDGEESTDRTPLLPGAPRAEAAPVCCSARYNLAILAFFGF

FIVYALRVNLSVALVDMVDSNTTLEDNRTSKACPEHSAPIKVHHNQTGKK

YQWDAETQGWILGSFFYGYIITQIPGGYVASKIGGKMLLGFGILGTAVLT

LFTPIAADLGVGPLIVLRALEGLGEGVTFPAMHAMWSSWAPPLERSKLLS

ISYAGAQLGTVISLPLSGIICYYMNWTYVFYFFGTIGIFWFLLWIWLVSD

TPQKHKRISHYEKEYILSSLRNQLSSQKSVPWVPILKSLPLWAIVVAHFS

YNWTFYTLLTLLPTYMKEILRFNVQENGFLSSLPYLGSWLCMILSGQAAD

NLRAKWNFSTLCVRRIFSLIGMIGPAVFLVAAGFIGCDYSLAVAFLTIST

TLGGFCSSGFSINHLDIAPSYAGILLGITNTFATIPGMVGPVIAKSLTPD

NTVGEWQTVFYIAAAINVFGAIFFTLFAKGEVQNWALNDHHGHRHDYKDD

DDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SLC17A5 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SLC17A5-DNA

(SEQ ID NO: 75)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

GTCAAACTAAGCAAAGGGTATGGAGAACTCACTGT

ACTATCTTTGCAACGTTTATGTAAACCTAAAATTT

CTAAAATAAAAAATATTAAAAAAAAGAATTCCTCT

GGTTTGAAGTCTTTCAAGTCTGTTGCAACTATATT

CCCTGGCCCAAGTTATCTATAACCTTGGTCATCTG

GGAGCTTGTTAGCAATACAGAATCTCAGGCACATC

CCAGATGTACTGGGCTTCTCAGAGAAACAGCCCCA

ATTGGGTAGTTTGGGTAATAAAGTTTTGGCTTTCA

CAATATAGGCTGGCCAACTCGACCCAAAACAGATG

ATGGTGCACATGCCTGGAGACCCAGGAGGACCTGT

GGTGCAGATGAAGTCTGAGGACACTCTGCTGGAGA

AGTCTCCCTTGCTTGGGCAAGAGAAGTGGGGGAGT

CGGATTTTTTATTCTAGATAGGCCTTCAACTGATT

GAAGGAAGCCCACCCAGATTATGGAAGGCAGCCAT

CTTTACCCAGAGTTCAATGATTTTAGTGTTAACCT

CATCCAAAGACAACCAGCAAGTTAACACATAAAAT

TAACCATCACACCAGATCTGCTGAATCTGAATCTA

CATTTTAAAAGGATTTGCCAGGTGACTCTGCATAA

TCCAGTTTGAAAATTGCATTTTTCTACAACCCTTA

GAGAGTGTAAAAATCTACATGGTAATTCAGTAACT

CAGAAACAAGGCTTGATTTGCTGCTTTAACTTGAG

AACTTTTCTAGCATTTACTGATCTGGAGGTAGGGA

TGCCTACAGAAATCCTCGCCCTCCCTTCTAGGTAA

AGGACCCTCCCCTTTGTTCTCACGTGAACCTCACT

AAGCTTCTAACCTGGTTTACTGAATTAGTGGCTTG

TGGGTCTTCCCTGTCTACACCAAACTCTCCGAGAG

CATCTACATCTTATTTTCTACCTCCACAGAGACAG

CCTTTATTGGCGGATCCAGATCTGCCCTGCCAAGG

CAAGCTGGGTTTTCCTAGTTTCACTTTCAGAGTCC

GCAAATGCTAGCACAATCTATCCAAATTCTATCGT

GGAGATAAAGCATGCACACATACATCAGAGGATTC

CATAGGTCGAACCATATGAAACTACCTATGTTGAT

TACTTTTACCTATAAAACCAGCAACATCATAGGAC

TCAACAAATTTCCATTGCTGTTTTTCCGCCTAAAA

GCTATTTTAGGACCAGGAGCAGTGGCTCACGCCTG

TAATCCCAGCACTTTGGGAGGCCGAGGAGGATTGC

TTGAGCCCAGGAGTTCGAAACCAGCTTGGGCAATA

TAATAAGACCAAGCCTCTACAAAAATAAAAAGTAG

AAACAAAATTAGCCAGATGTGGTGGCATGCTCCTG

TAGTCCCAGCTACTTGGGGGAGCTGAAGAGAATCG

CTTGAGTCCAGGAGTTGGAGGTTGCAGTGAGCTGC

GATTGCGCCACTGCATTCCAGCTTGGGCAACAGAG

CAAGACCCTGCCTGGGAGAAAAAAAAAAAAAAAAA

AAAGCTATTTTAGGGACAATATGCCGCCACAGTCA

CGAGGTAAATATGCCGCCACAGTCACGAGGTAGAT

CGTACAAAGGTTGCTAACAGTATGGCAACTGACCG

CTAACAAGCGAATGTCAAGTTGTGAAATGCACACC

ACCCACTTCCCTAGTTCGGTCGAAGCCCTCCCCTT

AATTATGTGCAATTCAAGTCCCCACTGCCCGCCCG

CAAGCCCCCACTCATCCTCGCTGCGGGCAGGGTGG

CCCCTGCACTTTACAAGGGGGTGCAGGAGCGGGAG

ACGGTCGTCCGAACACCGGCTCCCCGGCATGCGTA

GACCGGCGGGCGGAGCGGGCTCACTTTGCGCCAAT

CCTACGAGAACTCCCAGAACTCCGCTTCCCTAGTC

CAACCCAAGCCAGAGTTGCCCACACCTAAGATGGC

GGCGGGGGCGGAGTCGGCGCGGCCGCCTCTGGGCG

GGACCGCGGGGACTAGACGTGGCCGCGGGGCGGTGT

CAT

custom-character

ATGCGGAGCCCCGTGAGAGACCTGGCCAGAAACGA

TGGGGAAGAGTCTACAGACCGGACCCCGTTGCTTC

CGGGTGCTCCCAGGGCAGAGGCCGCCCCTGTCTGT

TGTAGCGCACGCTACAACCTCGCCATACTTGCTTT

TTTCGGGTTCTTCATAGTTTACGCCCTGCGGGTGA

ACCTTAGCGTAGCTCTTGTAGATATGGTCGACTCT

AACACTACTCTGGAAGACAACAGAACCTCTAAAGC

GTGTCCAGAGCACTCAGCCCCTATTAAGGTACACC

ATAACCAAACCGGAAAAAAGTATCAGTGGGACGCG

GAAACCCAGGGGTGGATACTCGGCTCATTTTTCTA

CGGTTATATTATCACCCAGATTCCTGGAGGCTATG

TAGCCTCCAAGATCGGTGGGAAAATGCTCTTGGGA

TTCGGCATTTTGGGTACTGCGGTACTTACCCTGTT

CACTCCTATAGCAGCCGATCTTGGGGTTGGCCCAT

TGATCGTTCTCAGAGCCCTCGAAGGTCTGGGAGAG

GGCGTTACATTTCCAGCAATGCACGCGATGTGGTC

AAGTTGGGCGCCACCCTTGGAGCGAAGCAAACTTC

TCTCCATTTCATATGCAGGGGCCCAGCTGGGAACT

GTAATAAGTCTGCCGCTGAGCGGTATAATCTGCTA

CTATATGAATTGGACATACGTCTTTTATTTTTTCG

GAACAATAGGGATTTTCTGGTTTCTCTTGTGGATA

TGGCTGGTTAGCGATACCCCGCAGAAGCACAAACG

CATAAGTCACTATGAAAAAGAGTACATCTTGTCTT

CACTTCGCAATCAACTGTCTTCTCAAAAGAGCGTG

CCTTGGGTACCGATATTGAAGAGCCTGCCTCTCTG

GGCAATCGTAGTAGCGCACTTTTCATATAATTGGA

CCTTTTACACACTGTTGACTCTTCTCCCAACGTAT

ATGAAGGAAATTCTCCGATTTAACGTGCAAGAAAA

TGGATTCTTGTCATCACTTCCTTACTTGGGTTCAT

GGCTCTGCATGATTTTGTCTGGTCAGGCGGCCGAT

AATCTGCGCGCCAAATGGAACTTTTCTACCTTGTG

TGTAAGACGAATCTTTTCCTTGATCGGCATGATAG

GCCCCGCTGTGTTTTTGGTAGCAGCCGGCTTCATT

GGGTGCGATTACTCACTGGCTGTCGCGTTTCTCAC

AATTTCTACCACACTTGGCGGTTTTTGTAGCTCTG

GCTTCAGCATAAACCATCTCGACATAGCACCTTCC

TACGCGGGTATACTGTTGGGTATCACAAATACCTT

TGCCACAATCCCAGGTATGGTCGGCCCAGTTATAG

CCAAATCTCTGACTCCTGACAATACTGTAGGAGAA

TGGCAAACAGTATTCTATATCGCCGCTGCTATCAA

TGTTTTCGGGGCAATTTTCTTCACGTTGTTCGCGA

AGGGGGAAGTCCAAAACTGGGCTCTTAATGACCAT

CATGGGCACAGGCACGACTACAAGGATGATGATGA

TAAGTA

custom-character

The CLN6 protein sequence is:

(SEQ ID NO: 76)

MEATRRRQHLGATGGPGAQLGASFLQARHGSVSADEAARTAPFHLDLWF

YFTLQNWVLDFGRPIAMLVFPLEWFPLNKPSVGDYFHMAYNVITPFLLL

KLIERSPRTLPRSITYVSIIIFIMGASIHLVGDSVNHRLLFSGYQHHLS

VRENPIIKNLKPETLIDSFELLYYYDEYLGHCMWYIPFFLILFMYFSGC

FTASKAESLIPGPALLLVAPSGLYYWYLVTEGQIFILFIFTFFAMLALV

LHQKRKRLFLDSNGLFLFSSFALTLLLVALWVAWLWNDPVLRKKYPGVI

YVPEPWAFYTLHVSSRHDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN6 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN6-DNA

(SEQ ID NO: 77)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

AAAGGCAGATGTGTTTGTATTTAAGAGATTGGAGG

ATTAAATGAGCTAGAGAGGCTCCCTCCACACGGCC

TCATCCTCTGATGGCTGGAAGCCCACCTCTGAGTG

TTATTAAATCGATGATGACATCATGGGCACTGCAT

GCCCCTCCCTCTGGAGCCCAGCAGGCTTGCAAAGC

CTGCAGAGGATAAGAAATTGGGGTCAGAGCGGGAA

GCCTCAATCCTTCTTCTCTGGTGTATACCGAGATC

GATGTGTAGATCAGATTCACCAGAATTAAATCTGG

GGCCCCGTCTGAGTGCTGTCCTTGGCTGACCCTTG

GGCACAGTACTTCAGCTCAGGGCCTAGGTTTTTCT

CTGCTACAAAACAGAGACAATCACCTGTTCTCCTT

ACGACCTGGTGTGTGTGGATCAAATGAAACAAGGA

AAGCTTTAAAGCAAATGTGTTCTTCAGGGGACCAG

GGGCGGAGGGGGGGGATTGAGGTGTGGCCTGTGGG

CTGCTAGAGCCCAGGATGGGGCTGATGGAAAATGA

CTCCCAGGCAGGCAGTCCTAGCCTCCCACAGCCAA

GAAAGGACATGCAGGTTCTGACCAAAGGGGAAAGA

AATAAATCCAATAAACATCTCCCAAGAAGAAAGAC

AGGAAAGAAAATAGAATGGAAATAGGCATAGCTCA

GACCCCTCATGGTCTGGGAAGCAGACCAAGGATAC

TGGGCAGGGGAATGGCACATTGCATTTGCATCTGA

GGCACATCCCTTCCAAGAGGCACATCCCTTCTGCA

GCGGCTTGAGGGCTGGGTGAGAGGAGACAGGACTG

GAGACCTGCACATGTCGTGTGCGCCTGGTGTAGCA

CGGGGGTGGTGGGGAGAATGGGAGTTGGTTGCAGT

TGTTCTAGTTAGCGGCCTGGGCTGCTGACAGTGAC

CGTGGGGAGGAGAGAGTTTGTGACATTGACAGTGG

TGTGGAAGGTAACCTTTCTGTGGAGGGAAACCTCA

GGTCTCGAGACGGGCTATTGTAAATAACTTAGTCC

ACCAGTGCTGGGCTCTCTGCTAAGAGTTTCATATA

GTCATCACAACTCCAATGTAGTAGATGCAATAGGC

ATCTTCTTGTTACAGATGAGTAAACTGAAGCTGTG

AGGGGTTGAGCCATTTGCCCGCATCACAGCTAGTT

CAAAGTGGTACCACTAATGAAGTCCTGGCAATCTG

CCCTGCAGGCTGTTCTCAGGTTTGACCTTTGGTTC

TGTTTTTCACTTGAGGATGCTGTCCCCTTAGGTTC

TGTCTGTCTTGTATGCTCCGGTGACTCACGAGCCT

GTCCACTGGGTTCCCAGGTCTCGCCTCAGCTTCAG

ACCACCGGTCCAACAGCCTTCCTGACCCACCTCAA

GCTTAATGCGTTCAAAGATGAATCTTTATTTACAC

GAAATCTGCTCTAGCCCACTTCCCGGGGGGTGCCT

CCACTATCCACCCAGGGGCAGAATCCGGCCACTGC

CTGAACTCTTCTCCCCTCACCCCCCACATCCAGAG

TCCCAGTCACCATACCTCTCACACGACTCTAGATG

TCACCAACTCGCTCCTTCCCACTGTCACCGCCAGC

CCCTCACTAGAACATCTGCAACCCACGTGCTGCAC

CACGCGGGTGCTACACGTGCAGGTCTCCAGTCCTG

CCTCCTCTCCTCCACCCGTAAGAACAAGGGAAATC

CCACAGAACCCTCTGCCCCGGGGAGCATTTAAATC

AGCTTAGTCTATCTCCAGGTCGCTACCCCGCCCCA

GCCCAACACCCAGGCCTCAGTCACCCTAGACAGAG

ATTCCCGTACCCAGGCAGGCAAGGGACCCTAACAC

ATCCCAGCCCGCTGGTGGTCACGCGCGCAGCCCGG

ACAGGCCAGCAGCCCCCGCCCCGCGAGGACGCCAC

ACTCGCAGCGCCCGGCCCTCCCCTAGCGGAGCCCG

CCCCGTCTCCCTCCGCCCCGCCTCCCTCCGCTCCG

CTCCGCTCCGCTCCGCCCCGCCCCGGGTCCGCAGC

CCCG

custom-character

ATGGAAGCCACTAGAAGAAGACAACACTTGGGAGC

GACAGGTGGACCCGGTGCGCAGTTGGGAGCCTCCT

TTCTTCAAGCTAGGCATGGTAGCGTAAGTGCTGAC

GAAGCCGCACGCACTGCACCTTTCCACTTGGATTT

GTGGTTTTATTTCACCCTCCAGAATTGGGTTCTGG

ATTTCGGGCGACCCATCGCAATGCTGGTGTTCCCG

CTTGAGTGGTTCCCCCTTAATAAACCCAGCGTGGG

AGACTATTTTCACATGGCATACAACGTGATAACCC

CTTTCTTGCTCCTTAAACTCATAGAGCGCAGCCCC

AGAACGCTTCCCAGAAGCATAACGTATGTGTCCAT

TATTATCTTCATAATGGGTGCCTCAATACACCTTG

TCGGAGATAGCGTAAATCACCGACTCCTCTTTTCA

GGATACCAACACCACCTGAGTGTTAGGGAAAACCC

GATTATTAAGAACCTCAAACCTGAGACCCTTATTG

ATTCTTTCGAGCTGCTGTACTATTACGACGAATAC

TTGGGTCATTGTATGTGGTATATTCCATTCTTTCT

CATTCTCTTCATGTATTTTTCTGGGTGCTTTACGG

CAAGCAAGGCGGAGAGCCTTATCCCAGGCCCCGCG

CTCCTTCTTGTTGCCCCAAGCGGTCTCTATTATTG

GTATCTGGTAACCGAGGGGCAAATATTTATACTTT

TTATTTTCACCTTCTTTGCCATGCTCGCCTTGGTT

TTGCACCAGAAGAGGAAGAGATTGTTCCTCGATAG

CAACGGACTTTTTCTGTTCTCTTCCTTCGCGCTTA

CCCTTCTCTTGGTAGCCTTGTGGGTCGCCTGGCTG

TGGAATGACCCAGTTTTGCGGAAAAAGTATCCCGG

TGTGATCTACGTGCCTGAACCTTGGGCATTCTACA

CTCTTCATGTGTCCTCTAGACACGATTATAAGGAT

GATGATGACAAATA

custom-character

The CLN8 protein sequence is:

(SEQ ID NO: 78)

MNPASDGGTSESIFDLDYASWGIRSTLMVAGFVFYLGVFVVCHQLSSSLN

ATYRSLVAREKVFWDLAATRAVFGVQSTAAGLWALLGDPVLHADKARGQQ

NWCWFHITTATGFFCFENVAVHLSNLIFRTFDLFLVIHHLFAFLGFLGCL

VNLQAGHYLAMTTLLLEMSTPFTCVSWMLLKAGWSESLFWKLNQWLMIHM

FHCRMVLTYHMWWVCFWHWDGLVSSLYLPHLTLFLVGLALLTLIINPYWT

HKKTQQLLNPVDWNFAQPEAKSRPEGNGQLLRKKRPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN8 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN8-DNA

(SEQ ID NO: 79)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

TGAAATCGTATGGATCAAAGCTGTCCTCTTGGCCT

GAGCCGGTTGCTGAGTGCGGGCCACAAGATCAGAT

GAGCCAGTTTATCCATCTGGATGGTCCCAGCTAAT

TCAGCAAGTGCAAGGTCTGCAAAATATCTCAAGCA

CTGTTGTTAGGTTTTTCAATAGTGATGTTATCCCC

AGGAGCAATTTAGGGAGGGTCAGAATCTTGTAATC

TCCAGCTGCATGAATTCTAAACCATAATTTCTAAT

CTTGTGGCTAATTTGTTAGTCCTACAAAGGCAGTC

TAGTCTCCAGACAAGAAAAGGATTTGTTTCGGGAA

ACCATAAACTAAGTTTCTTCCAAAGTTAGTTTGGC

CTACACCCAGGAATGAACAAGGACAGTTTGGAGGT

TAAAAGTAGGATGGAGTTGGTTAGGTCAGATCTCT

CACTGTCTCAGTTATAATTTTGCAATGGTGGTTTC

ACTGGTTTTAAGATGGAGTTTATTTTATTTTATTT

TTATTTTTTTGAGACAGAGTTTCATTCTTGTTGCC

CAGGCTAGAGTGCCATGGCGTGATCTCAGCTCACT

GCAACCTCTGCCTCCTGGGTTCAAGCAATTCTGCT

TCAGCCTCCTGAGTAGCTGAGATTACAGGTGCCCA

CCACCACACCCGGCTAATTTTTTTCTCCCAAACTG

CTGGGATTACAGGCTTGAGCCACCGCGCCCGCCAA

GATGGGTTGTTGATTTTAAAACGATGTCACCCTGG

CTCTCCTAGGTTCCTGTTCCCCTAACATCATGAAG

GCTGCTGGCAGTTCTCTGGCCTCCAGGGAGGCCTC

CACACACATTTACCCATGTTCTTAGACAATCCTAG

GGACTCAAGGCTTCAACAAACCTAAATGAGCCAGC

AGAAAAATAAACTTGAACATGAATGTCAACGTTTT

CCCACATGTACTAAAGGGTTATAATAATTTTGAAA

TGTTTATTTCAAAGAGCGTTGGTAATTTAAACGTC

CTATTTAATCCCCAAAACAGTCCTGAGGGGGAGAT

AAGGCAGTTATCTTCATAGTACAGGAAAGGAAAAA

AGCGAGGGTCCAAGGCCGACTATACCCTCAGCTCC

ATTAGCCCCCGAGGCCTCCCTGACAGGCGGGGCGG

ACAATCCCAGTGCAGATGCTCTGTATCGATCGCAT

GCTATCGGTTCTTTCAAGGAACGTGTATTGATCAT

CAATTAAGTGGTGAGTACTCCTCTAGATGTCGATT

CTAAAGAGGGAACAAAACACATTAGACAGAAGAAA

CATAAGTAACTCGAATAACAACCTTAGAGAGAAGA

AACATAAGTAACTCGAATAACAACCTTAGCAAACT

GCGGAAACTCCTACAGACAAAAACTCAGGTGTGGG

CGCAGAAGGGCCGGGGATGCGCTCGGTCAAGACTT

GAAGGTCCGGGGCTTGGGCCCTGTGTCCTCACCGA

GCCCCGGGGAGGCTCCGGCTCCGTCCACACCCGGA

GCGCGACTCAGCCGCGGCCGGGGCTCTTCTGGAGA

ACGGCGCGGTCAGGCTCTGCCGCAGCTTTCAGGTC

CCCTCGGCCCCGTCCGGGTGCAGCGCAACCAGGCT

GCCCGCGGAGCCCCACCGCCCCCATGCCGCCGCCC

GCCATGGTTCAGCCCGGCCCCGCCCCTCCCGCCGG

CCGTGGTTCAGCGCGTCCACCCCGCCGCCCCACAG

CGCCCGCCGCGCCGCGCCCCGCCCCCCGCCGCGCC

CCGCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCC

CGCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCC

GCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCG

CCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCGC

CCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCGCC

CCCCGCCGCGCCCCGCCCCCCGCGCCGCGCCCCGC

CCCCCGCCGCGCCCCTCCCGCGCCCGCCGCCCCGC

CCCTCCCGCGCCCGCCGCCGTCGTAGCGCCTAGGC

GGGGCCTCTCGTAGCGACGCCCCCAGGGGGGCAGA

ACGCGTGCGCACGCGCGTGCGAACGCGCGTGCGCG

GGCGGTGTTTGAGGCCGGC

custom-character

ATGAATCCCGCGAGTGATGGCGGCACTTCAGAGAG

TATCTTTGACTTGGACTATGCATCATGGGGGATAC

GCTCAACTCTTATGGTTGCAGGGTTCGTATTTTAT

CTGGGGGTTTTTGTTGTCTGTCACCAACTTTCCAG

CAGTCTCAACGCCACTTATAGATCCCTTGTGGCTA

GGGAGAAAGTCTTTTGGGACTTGGCCGCAACCCGA

GCCGTTTTTGGTGTCCAGTCCACGGCGGCTGGACT

GTGGGCCCTCCTTGGTGATCCTGTTCTGCACGCTG

ATAAAGCCAGAGGCCAACAGAACTGGTGTTGGTTC

CATATAACTACGGCGACTGGCTTCTTTTGTTTTGA

AAACGTAGCCGTACACCTGTCCAATTTGATCTTCA

GAACATTCGACCTCTTTCTGGTAATCCACCATCTT

TTCGCCTTTCTCGGCTTTCTTGGATGTCTTGTCAA

TCTCCAAGCCGGTCACTACCTCGCAATGACTACTT

TGTTGCTCGAAATGTCAACCCCATTTACTTGCGTA

TCATGGATGCTGCTGAAAGCGGGATGGAGTGAATC

ACTTTTTTGGAAGTTGAATCAGTGGTTGATGATTC

ATATGTTTCACTGTCGAATGGTACTGACATATCAT

ATGTGGTGGGTCTGTTTCTGGCACTGGGACGGGCT

GGTATCTTCACTTTATCTCCCTCACCTGACCCTTT

TCCTCGTAGGCTTGGCGCTGCTCACACTGATCATT

AATCCTTACTGGACCCACAAGAAAACGCAGCAACT

GCTGAACCCTGTGGATTGGAACTTCGCACAGCCCG

AGGCCAAGTCACGGCCTGAAGGCAACGGTCAACTG

TTGAGGAAGAAGAGACCGGACTATAAGGATGATGA

CGACAAATA

custom-character

The GM2A protein sequence is:

(SEQ ID NO: 80)

MQSLMQAPLLIALGLLLAAPAQAHLKKPSQLSSFSWDNCDEGKDPAVIRS

LTLEPDPIIVPGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCT

DYIGSCTFEHFCDVLDMLIPTGEPCPEPLRTYGLPCHCPFKEGTYSLPKS

EFVVPDLELPSWLTTGNYRIESVLSSSGKRLGCIKIAASLKGIDYKDDDD

K

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GM2A and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GM2A-DNA

(SEQ ID NO: 81)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

CCCAGATACAGAATCTTCTTGGGTCCAAATACCCC

CTAGAGGTTTCCCATTGGCCACTTGGTGCTCACCT

CATGTAAATGAAGTGGTGGCCCGCAATCAGTCTGA

CTGGTTAATCAGAGGCCGAAGTGAAGTTACAAAGG

TCATGCTCCTGTGCAAACATCTGATTGGTTGTGGA

AAGCAACCAATCAGGCTGAAGTGAAGTTACAAAGT

TGCACTTCTATGCAATTTTAACATATAAACTGAAA

TGTAGCATAGAAATCGAAATGTACTTTCAATTTCC

CATCTGCTGCACAGAAAAGGTGGGGGGTTGTAAAG

AGAGTAGCCTCTGGTCCTCTTGTTACTTAGGTGTG

GAAAGTTAGGGTTTTCCTTTCGATTTAGTTCTAGG

AAGTCAGCGTGAAATGGCCTTAGGTTCCCTGCCTG

CAGACTCTATTCTCCTACCTCAGTTGGGCTAGGTG

AAAGGGAAGAGTTGATCAGAATGGGAGGATCATTA

TGTAAAGTATGGAGCTTAGTTAATAATAGTGTACC

AATGTCATGCCCTCAGATTTAAAAAAAATTTTTTA

ATTTTTTATTCTTTTGCCACCTCCTTGTCGCTGGC

AGTGCCCCCCAGTTATGCACAAGCACAAGCTCTGG

GTCTGCAGTCTGAACCCCCGGCCAGGCCACGGGTG

TCTTATCAACAATAGAGGAAACGAACAGAACTTTG

TAGTATTTTTGCAACTTTTCTGTAAACCAAAATAA

AAAGTTTACTTTAAAAAAGATGATCAGGTGAGTTT

TAAATTCTACACATGCATTCATGTACTCAACAGAT

TGTCTATTATGCATCAGGCACTGGGTATAAATGAG

TGCCTGCATCATGATGCCACCCCTTGTGTAGTTTA

CAATCCTGTGGTAAATTGGCGGTATTGGTAACAAC

ATCCCTGTTTTTTCTAAAAGCAAATCTCCAACTAG

TATATTAACCTGACAAAATCTTGGCTGATGGGGTG

TCTAAAAAGAAGTCTTGCTCTATTCCTTCCTAGCT

GTGCGACCTTGGCAGAGCTAACCTCACTGTGTATC

AGTTTCCTCAGTGCTAAAATTGGGGAAGAAAAAAA

AAAAGCATTCCCTTGTGCGTCCTTAGCATGCTTTC

AAGCAGTTACTAAATGTTAGTTTTTATAACGGTTA

TAATTATTAAAAAGATACGGATTCGTGAAGTCAAG

AGATCAAGACCGTCCTGGACAACACGGTGAAACCC

CGTTTCTACTAAAAACACAAAAATTAGCTGGGCGT

GTGGCGCGTGCCTGTAGTCCCAGCTAGTCGAGAGG

CTGAGGCGGAAGAATCGCTTGAACCTGGGAGGCAG

AGGTTGCAGTGAGCCGAGATCGCGCCACTGCACTC

CAGCTCGGGCGACAGAGCGAGAGTCCGTCTCAAAG

CAAAAAAAAAAAAAAAAAAGACACACATATGGGGA

AGCGTAACATGGCAGAGAGTCTGACATTTTTGTCC

GGAAGGACTTGGGGATGAAAACACTGAATCCGCGG

TTTCCCAAAGGTCCTTCCAAAGGTGACGGCCCCGG

CACGAGTTCACAAACCACAGCTCCGCCCCATCCCC

TGCCCGGCCCCGCCCTTCCCAGGAGCTCTGCTCCG

CCCCGCCCCCGACTCCGCTCGGCCCCTCCTCGCGC

CACGCCCCCGCCCCTCCCGCGCGCGCAGCTCCGCC

CCGCCCTCGTGATCCCGCCCCAACCTCGTGCTAAG

CTCCCTTCCGTTCCAGCCGCCTTCAGCCCCGCCGC

GCTCAGTTCCGCCCCTTTCTCTTCCAACTCCGCCT

ACGCCCCAGAGAGGGAAGGCCTTGACACCTACGCT

AGAGAGACAGGCTCCAATGAAAAGAGCGAGGGGGC

GGAGCCGGGAGGAATCGGTCCAATTCTCGGCCGGG

AAGTCTCTGGCCGGGACGGGGCAGGGCGAACCTGC

CAGTGACTGGACTCAGCTTCTTTGCGTAACCAATA

CTGGAAGGCATTTAAAGGCACCTCTGCCGCCACAG

ACCT

custom-character

ATGCAGTCTCTCATGCAAGCTCCTCTCTTGATCGC

CCTTGGTCTGCTTTTGGCTGCCCCAGCACAAGCTC

ACCTGAAAAAACCTTCCCAACTTAGCTCCTTTTCC

TGGGATAATTGCGATGAAGGAAAGGACCCGGCTGT

AATCCGAAGTTTGACACTCGAACCTGACCCCATCA

TCGTCCCGGGCAATGTCACGCTTTCAGTAATGGGT

AGCACGAGCGTTCCGCTCTCTAGCCCATTGAAAGT

AGACCTCGTGTTGGAAAAAGAAGTAGCCGGGTTGT

GGATAAAAATTCCATGCACGGATTATATTGGCTCA

TGTACCTTTGAACACTTTTGCGATGTTTTGGACAT

GTTGATCCCCACAGGCGAGCCATGTCCAGAGCCCC

TTAGGACGTATGGGCTTCCGTGTCACTGCCCATTC

AAGGAAGGTACATATAGCCTGCCGAAGTCAGAATT

TGTCGTCCCTGATCTCGAATTGCCTAGTTGGCTGA

CAACCGGCAACTATCGAATTGAATCTGTACTTTCT

TCAAGCGGTAAACGGCTCGGCTGTATCAAAATAGC

CGCCTCCCTGAAGGGGATAGACTACAAGGACGACG

ACGATAAATA

custom-character

The HYAL1 protein sequence is:

(SEQ ID NO: 82)

MAAHLLPICALFLTLLDMAQGFRGPLLPNRPFTTVWNANTQWCLERHGVD

VDVSVFDVVANPGQTFRGPDMTIFYSSQLGTYPYYTPTGEPVFGGLPQNA

SLIAHLARTFQDILAAIPAPDFSGLAVIDWEAWRPRWAFNWDTKDIYRQR

SRALVQAQHPDWPAPQVEAVAQDQFQGAARAWMAGTLQLGRALRPRGLWG

FYGFPDCYNYDFLSPNYTGQCPSGIRAQNDQLGWLWGQSRALYPSIYMPA

VLEGTGKSQMYVQHRVAEAFRVAVAAGDPNLPVLPYVQIFYDTTNHFLPL

DELEHSLGESAAQGAAGVVLWVSWENTRTKESCQAIKEYMDTTLGPFILN

VTSGALLCSQALCSGHGRCVRRTSHPKALLLLNPASFSIQLTPGGGPLSL

RGALSLEDQAQMAVEFKCRCYPGWQAPWCERKSMWDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HYAL1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HYAL1-DNA

(SEQ ID NO: 83)

GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA

GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA

CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT

GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC

AATAATGACGTATGTTCCCATAGTAACGCCAATAG

GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA

CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA

TCATATGCCAAGTACGCCCCCTATTGACGTCAATG

ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC

ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT

CTACGTATTAGTCATCGCTATTACCATG

GGACTTGCTGGTGACACAGCCTCAGGAAGTCCTGA

GGACATGTGCCCAGGGCGGTTGGGGCACAGCTTGG

TTTTATAGATTTTAGGGAGACATGAGACATTAATC

AATATGTAAGAAGTACATTAGTTCCAGAAAGAAAG

GTGGAGACTGCTCAAATCAAGGCTCCCAGGCTCAA

AGCACTGGGGGCTTCCAGGTCACAGATAGGTGAGA

GACAGATGGTTGCATTCTTTTGAGTTTCTGGTAAG

TCTTTCCAAAGGAGGCAATCAGAATATGCATCTAT

CTCTGTGAGCAAAAGGATGACTTGAATAGAATGGG

AGGCAGATTTGTCCTGAGCAGTTCCCAGCTTGAAG

AGGCCCAAGATACTTTCCTTTCACATTTACCCCAT

TTTCTTTTTCAAAATCTTTTGGAGAAAGCATTTTG

CAAGAAAATGAGTATCTGGTCTCAGGTTTCATCTG

ATCTCTCATTGCTAGATAAGTAGGTCCGGAAAGCT

CATTTTTAGCAGGTTGTAAAGTCTCATGCAGTGTG

AAGAGAAAATAGGGAGAAGGAAGGAAGAGAAAAAA

AAAACAGCAAAAGAACAATCCCAGCCCTGGCGGGG

TGGCTCATGCCTGTAATCCCAACAATTTGGGAGGC

TGAGGCGGGTGGATCACCTGCGGTTGGGAGTTCGA

GAACAGCCTGACCAACATGGAGAAACTCTGTCTCT

ACTGAAAATACAAAAAACTAGCCAGGCATGGTGGC

TCATGCCTGTAATCCCAGCTACTCAGGAGGCTGAG

ACAGGAGAATCACTTGAACCCAGGAGGCGGAGGTT

GCAGCAACCTGACATTGCGCCATTGCACTCCAGCC

TGGGCAACAAGAGTGAAACTCCATCTCAAAAAAAA

AAAAAAAAAAAATCCTGGGAAAATATAGGCCACAT

TACTCTGAAGTCCATACATTGGTAGGCAGGTATGA

AAGTGGCTTATGTATGTACATAAACAGGTTACTGT

TACTTTCTTCTGAAGTGTAAGTTGTCTGACTTTAG

TTGACACGCTTTTAAGAAACCACAGCTAGGGCCGG

GCGCAGTGACTAACGCCTGTAATCCCAGCACTTCG

AAGAGGCCGAGGCGGCCGGATCACAAGGTCAGGGT

TCGAGACCAGCCTGGTCAATATGGTGAAACCCTGT

CTCTACTAAAAATACAAAAATTAGCCAGGCATGGT

AGCAAGCGCCTGTAGTCCCAGCTACTCGGGAGGCT

GAGGCAGGAGAATTGCTTGAACCTGGGAGGCATAA

GTTGCAGTGAGCTGAGATCGCGCCACTGCACTCCA

GCCTGGGTGACAGAGCGAGACTCCATCTCAAAAAA

AAAAAAAAAAGAAACCACAGTGGCCGATTGCAGTG

GCTCCCCCTCCCCCTCCCCCTCCCCTCCCCCTCCC

CCTCCCCCTCTCCCTCCACGGTCTCCCTCTGATGC

CGAGCGGAAGCTGGACTGTACTGCTGCCATCTCGG

CTCACTGCAACCTCCCTGCCTGATTCTCCTGCCTC

AGCCTGCCGAGTGCCTGCGATTGCAGGCACGCGCC

GCCACGCCTGACTGGTTTTCGTATTTTTTGGGTGG

AGACGGGGTTTCGCTGTGTTGGCCGGGCTGGTCTC

CAGCTCCTAACCGTGAGTGATCTGCCAGCCTCGGC

CTCCCGAGGTGCTGGGATTGCAGACGGAGTCTCTC

AATGGTGCCCAGGCTGGAGTGCAGTGGCGTGATCT

CGGCTCGCTACAACATCCACCTCCCAGCAGCCTGC

CTTGGCCTCCCAAAGTGCCGAGATTGCAGCCTCTG

CCCGGCCGCCACCCCGTCTGGGAAGTGAGGAGCGT

CTCTGCCTGGCCGCCCATCGTCTGGGATGTGAGGA

GCCCCTCTGCCTGGCTGCCCAGTCTGGAAAGTGAG

GAGCGTCTCTGCCCAGCCGCCATCCCATCTAGGAA

GTGAGCAGCGCCTCTTCCCGGCCGCCATCCCATCT

AGGAAGTGCGGAGCCTCTCTGCCCGGCCACCCATC

GTCT

custom-character

ATGGCAGCGCATCTCCTCCCGATATGTGCACTTTT

TCTGACTCTTCTTGATATGGCACAAGGATTTCGGG

GTCCGCTCTTGCCTAATCGACCTTTTACAACAGTA

TGGAATGCTAACACACAGTGGTGCCTTGAAAGGCA

CGGTGTCGACGTTGACGTCTCCGTCTTCGACGTAG

TAGCCAATCCAGGCCAAACCTTCAGGGGGCCAGAT

CATGACTATCTTCTATAGTTCTCAACTGGGGACTA

TCCCTACTACACCCCCACGGGTGAACCTGTATTCG

GCGGGTTGCCACAGAATGCTAGCCTTATCGCGCAC

CTGGCCAGGACGTTTCAAGACATACTCGCCGCCAT

TCCAGCACCCGACTTCTCTGGTCTGGCTGTGATCG

ATTGGGAGGCCTGGCGACCTAGGTGGGCTTTCAAC

TGGGATACCAAGGACATCTATAGGCAGCGGAGCCG

AGCATTGGTGCAAGCCCAGCATCCGGATTGGCCAG

CGCCTCAGGTGGAAGCGGTAGCGCAGGATCAATTC

CAGGGCGCCGCGAGAGCTTGGATGGCCGGGACATT

GCAACTTGGGAGAGCCTTGAGGCCTCGCGGCCTGT

GGGGTTTTTATGGATTCCCAGATTGCTACAACTAT

GATTTTCTCTCTCCAAATTACACAGGCCAATGTCC

AAGCGGCATACGCGCACAGAACGATCAGCTTGGCT

GGCTCTGGGGACAATCTCGAGCCTTGTACCCTAGC

ATCTATATGCCAGCTGTCTTGGAGGGCACCGGAAA

ATCTCAGATGTACGTGCAACATAGGGTTGCAGAGG

CCTTCCGGGTTGCCGTCGCAGCCGGAGATCCGAAT

CTGCCTGTTCTTCCCTATGTACAGATCTTTTATGA

TACCACAAATCACTTTTTGCCGTTGGACGAGCTTG

AACATAGTTTGGGTGAAAGTGCGGCCCAAGGTGCG

GCGGGAGTAGTTCTTTGGGTTTCCTGGGAAAATAC

ACGGACTAAAGAGTCATGTCAGGCCATAAAGGAGT

ACATGGATACCACACTGGGCCCTTTCATTTTGAAT

GTTACGAGTGGCGCGTTGCTTTGTAGTCAGGCACT

GTGCAGCGGACACGGCAGGTGTGTGCGGCGGACGT

CACATCCAAAGGCCCTGCTGCTGCTGAACCCGGCG

TCATTTTCAATTCAACTTACTCCCGGTGGGGGGCC

CCTCTCACTTAGGGGCGCGCTCTCCCTGGAAGACC

AGGCCCAGATGGCAGTAGAGTTTAAGTGCAGATGT

TACCCAGGGTGGCAGGCGCCTTGGTGCGAGCGCAA

ATCCATGTGGGATTACAAAGATGATGATGATAAGT

A

custom-character

In certain embodiment, any of the GOI described herein are codon optimized for manufacturing, optimal expression in a host cell, such as in a human cell. Further Codon optimization of GOI can be done based on codon optimization table publically available, such as the Codon and Codon Pair Usage Tables (CoCoPUTs) maintained at the George Washington University (GWU). The CoCoPUTs is derived from all available GenBank and RefSeq data source.

In certain embodiment, the GOI's are codon optimized for expression in neuronal tissues or specific cell types in neuronal tissues, such as neurons, depending on the target cell type the GOI's are to be expressed. This can be done using TissueCoCoPUTs, which are human tissue-specific codon and codon pair usage tables derived from human genomic codon usage information and tissue-specific transcriptomic data. The TissueCoCoPUTs maintained by the GWU website represent 52 human tissues. Transcriptomic data are derived from the Genotype Tissue Expression (GTEx) Portal.

3. Delivery Methods

In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by intravenous injection or direct intraparenchymal injection or direct intracranial injection. Such delivery means effectively bypass the BBB, and are common means for the administration of gene therapeutics to the brain. In certain embodiments, the neuronal target cells intended to receive gene therapy through intraparenchymal injection are clustered in a focal location, and are this particularly suitable for focal delivery of the viral vector.

In certain embodiments, the viral vector (such as AAV) of the invention is delivered locally or compartmentally, such as direct intraocular injection, or injection in the cochlea.

In certain embodiments, the viral vectors of the invention are delivered to neuronal target cells by intravenous injection.

In certain embodiments, the neuronal target cells intended to receive gene therapy through intravenous injection are globally located in the CNS, or in multiple CNS regions. Such global delivery across the BBB is achieved by using selected AAV serotypes (such as AAV9) that have been shown to deliver genes across the BBB after intravenous injection.

In certain embodiments, the viral vector (such as AAV) of the invention is delivered to achieve widespread delivery for diseases of extensive pathology including glioblastoma multiforme (GBM), lysosomal storage diseases (LSDs), Alzheimer's disease, Parkinson's disease and Canavan's disease. In certain embodiments, the viral vectors are delivered intracerebroventricularly, intrathecally, intranasally, or systemicaly (e.g., intravenous and intra-arterial injections).

The systemic delivery route for gene delivery vehicles is very promising, and has the potential to be a conduit to the entire CNS (every cell in the brain is a maximum distance of 40 μm from an endothelial cell), provided that the issue of BBB blockage and the filtration systems of the spleen and liver are adequately dealt with.

In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by intravascular, intrathecal, and/or cerebrospinal fluid (CSF) administration. Many AAV capsids, such as AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10, have remarkable CNS tropism after vascular (Foust et al., Nat Biotechnol. 27:59-65, 2009; Gray et al., Gene Ther. 20:450-459, 2013; Zhang et al., Mol Ther. 19:1440-1448, 2011; Bevan et al., Mol Ther. 19:1971-1980, 2011; Yang et al., Mol Ther. 22:1299-1309, 2014; Duque et al., Mol Ther. 17:1187-1196, 2009), and CSF administration (Samaranch et al., Hum Gene Ther. 24:526-532, 2013; Gray, supra; Samaranch et al., Hum Gene Ther. 23:382-389, 2012).

In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by direct intracranial injection. A large range of AAV capsids, including pseudotypes rAAV2/1, rAAV2/2, and rAAV2/5, hu.32, hu.37, pi.2, hu.11, rh.8, hu.48R3, bb2, cy5, rh20, rh39, rh43, AAV7, AAV8, and AAV9, have been demonstrated for their CNS gene transfer properties by direct intracranial injection (Burger et al., Mol Ther. 10:302-317, 2004; Cearley et al., Mol Ther. 16:1710-1718, 2008; Cearley and Wolfe, Mol Ther. 13:528-537, 2006; Lawlor et al., Mol Ther. 17:1692-1702, 2009). Vectors based on distinct AAV serotypes or pseudotypes can be chosen for specific applications in the nervous system, depending on their preferential or global tropism within the different regions of the brain and target neuronal tissues.

In certain embodiments, the viral vector is AAV9. The vast majority (>90%) of cells in the CNS transduced by intravenously injected AAV9 using strong promoters like CBA are astrocytes and neurons. The distribution of vector is widespread with transduced cells detected in all areas of the brain from the olfactory bulb to cerebellum.

In certain embodiments, delivery of the viral vectors of the invention across the BBB is further enhanced by a variety of techniques including: intra-nasal administration and/or intracranial NSC transplantation that bypasses the BBB; transiently permeating the BBB using osmotic manipulation; magnetic resonance imaging guided focused ultrasound (MRIgFUS) to selectively open the BBB and allow therapeutics to pass into the parenchyma; convection enhanced delivery (Debinski and Tatter, Curr Opin Mol Ther. 12:647-653, 2010); introduction into a fluid space, e.g., vasculature, brain ventricles or intrathecal space in the spinal cord, such that cells lining the space produce the deficient protein (Chen et al., Nat Med. 15:1215-1218, 2009); injection into regions of the brain that serve as a nexus of interconnections with retrograde transport of vectors, such as the thalamus, e.g., for AAV (McCurdy et al., Sci Transl Med. 6:231ra48, 2014); and/or by taking advantage of the “bystander effect” whereby proteins released from the producer cells can be taken up by the deficient cells (McCurdy; Chen, Supra).

In certain embodiments, the viral vector (such as AAV) of the invention comprises a targeting peptide that bind selectively to the brain endothelial cells or a brain endothelial cell receptor (such as the low-density lipoprotein (LDL) and other related receptors that can be targeted by Apolipoprotein E-derived peptides) to target the viral vector to the brain vasculature.

4. Viral Production

In certain embodiments, the packaging cell line is a HEK293 cell line, a HeLa cell, or an A549 cell.

In general, the subject rAAV vector can be produced using any of many art-recognized approach. In certain embodiments, the rAAV vector is produced based on the helper-virus-free transient transfection method with all cis and trans components (e.g., vector plasmid and packaging plasmids, along with helper genes isolated from adenovirus) in host cells such as 293 cells. In certain embodiments, the rAAV vector is produced using recombinant herpes simplex virus (rHSV)-based AAV production system, which utilizes rHSV vectors to bring the AAV vector and the Rep and Cap genes into the cells. In certain embodiments, the rAAV vector is produced based on baculovirus system which requires simultaneous infection of insect cells with several baculovirus vectors to deliver the rAAV vector cassette and the Rep and Cap genes. In certain embodiments, the rAAV vector is produced based on the AAV producer cell lines derived from HeLa or A549, which stably harbored AAV Rep/cap genes. The AAV vector cassette can either be stably integrated in the host genome or be introduced by an adenovirus that contained the cassette.

AAV NATIVE-NEURO PLATFORM AND USE FOR NEURONAL DISEASE GENE THERAPY

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