Production of large-sized quasidystrophins using overlapping AAV vectors

Patent metadata

Field	Value
Publication number	US-12466864-B2
Application number	US-202017593285-A
Country	US
Kind code	B2
Filing date	Mar 25, 2020
Priority date	Mar 25, 2019
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

The present invention concerns a quasidystrophin (QD) having the structure CH1CH2H1R1R2R3H2R8R9 in its N-terminal part and advantageously further comprising the R16 and R17 rod domains, as well as the dual AAV vector system which allows producing it.

First claim

The invention claimed is:

1 . A dual AAV vector system comprising two AAV vectors, wherein
a first AAV vector comprises, between 5′ and 3′ AAV ITRs, a first nucleic acid sequence that encodes a N-terminal part of a quasidystrophin, and a second AAV vector comprises, between 5′ and 3′ AAV ITRs, a second nucleic acid sequence that encodes a C-terminal part of a quasidystrophin, wherein the first and second nucleic acid sequences comprise an overlapping region that permits the production by recombination of the quasidystrophin, wherein the quasidystrophin is encoded by a sequence according to SEQ ID NO: 22.

2 . The dual AAV vector system according to claim 1 , wherein the first nucleic acid sequence has the sequence SEQ ID NO: 6 or SEQ ID NO: 23 and the second nucleic acid sequence has the sequence SEQ ID NO: 7.

3 . The dual AAV vector system according to claim 1 , wherein the first nucleic acid sequence has the sequence SEQ ID NO: 8 and the second nucleic acid sequence has the sequence SEQ ID NO: 9.

4 . A cell transduced with the dual AAV vector system according to claim 1 .

5 . The cell of claim 4 , wherein the cell is a muscle cell.

6 . A composition comprising, in a pharmaceutically acceptable carrier, the dual AAV vector system according to claim 1 .

7 . The composition according to claim 6 , wherein the dual AAV vector system is present in a cell into which it has been transduced.

8 . An AAV vector which is the first AAV vector or the second AAV vector of the dual AAV vector system according to claim 1 .

9 . A method of treating muscular dystrophy in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a recombinant AAV comprising the polynucleotide sequence of claim 1 .

10 . The method of claim 9 , wherein the muscular dystrophy is Duchenne muscular dystrophy (DMD).

Assignees

• Genethon
• Inst Nat Sante Rech Med
• Univ Devry Val Dessonne

Inventors

• Richard Isabelle
• Lostal William

Classifications

• C12N2750/14171

  Demonstrated in vivo effect · CPC title

• C12N2750/14145

  Special targeting system for viral vectors · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C12N15/86

  Viral vectors · CPC title

• C12N5/0652

  Cells of skeletal and connective tissues; Mesenchyme · CPC title