Expression of full-length dystrophin reverses muscular dystrophy defects in young and old mdx4cv mice.

ABSTRACT: Gene replacement therapies mediated by adeno-associated viral (AAV) vectors represent a promising approach for treating genetic diseases. However, their modest packaging capacity (~4.7 kb) remains an important constraint and significantly limits their application for genetic disorders involving large genes. A prominent example is Duchenne muscular dystrophy (DMD), whose protein product dystrophin is generated from a 11.2 kb segment of the DMD mRNA. Here, we explored methods that enable efficient expression of full-length dystrophin via triple AAV codelivery. This method exploits the protein trans-splicing mechanism mediated by split inteins. We identified a combination of efficient and specific split intein pairs that enabled the reconstitution of full-length dystrophin from 3 dystrophin f

SUBMITTER: Tasfaout H 

PROVIDER: S-EPMC12321383 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature