Recombinant adeno-associated viral vectors for multipartite gene delivery and stargardt disease treatment
AssigneeAbeona Therapeutics Inc.
InventorsLinas PADEGIMAS, Brianna BARRETT
Life of this patent
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Abstract
Provided herein are recombinant AAV vectors, AAV vector genomes, AAV viral vectors, and capsid proteins for improved gene therapy, and methods for their manufacture and use in a multipartite (e.g., bipartite) delivery system. The vectors provide portions of transgene and direct their recombination in a cell to provide complete transgenes. Also provided are regulatory sequences (e.g., enhancer, promoter) that results in high level expression of the transgene (e.g., ABCA4), which are useful for gene therapy (e.g., Stargardt disease treatment).
Claims27
-34. (canceled)
An AAV vector genome comprising, in 5′ to 3′ orientation:
- (a) a 5′ AAV inverted terminal repeat;
- (b) (b-1) a Lox JTZ17 recombination site comprising or consisting of SEQ ID NO:
- 217, or a sequence having at most 1, at most 2, or at most 3 nucleotides mutations (deletion, insertion, and/or substitution) thereto;
- or (b-2) a Lox 66 recombination site comprising or consisting of SEQ ID NO:
- 179, or a sequence having at most 1, at most 2, or at most 3 nucleotides mutations (deletion, insertion, and/or substitution) thereto;
- (c) a splice acceptor (SA) site;
- (d) a 3′ portion of a transgene;
- (e) a poly-A site;
- and
- (f) a 3′ AAV inverted terminal repeat.
-48. (canceled)
(canceled)
-58. (canceled)
-73. (canceled)
A nucleic acid comprising a 5′ portion of an ABCA4 gene, wherein the 5′ portion of the ABCA4 gene comprises one or more of:
- (i) a nucleotide “G” at the position corresponding to nucleotide 813 of SEQ ID NO:
- 212;
- (ii) a nucleotide “A” at the position corresponding to nucleotide 1311 of SEQ ID NO:
- 212;
- (iii) a nucleotide “A” at the position corresponding to nucleotide 2274 of SEQ ID NO:
- 212;
- (iv) a nucleotide “C” at the position corresponding to nucleotide 2277 of SEQ ID NO:
- 212;
- (v) a nucleotide “T” at the position corresponding to nucleotide 2278 of SEQ ID NO:
- 212;
- and (vi) a nucleotide “T” at the position corresponding to nucleotide 2568 of SEQ ID NO:
- 212.
-78. (canceled)
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Dependencies are inferred from the claim text.