Split intein-mediated protein trans-splicing to express large dystrophins.

ABSTRACT: Gene replacement using adeno-associated virus (AAV) vectors is a promising therapeutic approach for many diseases^1,2. However, this therapeutic modality is challenged by the packaging capacity of AAVs (approximately 4.7 kilobases)³, limiting its application for disorders involving large coding sequences, such as Duchenne muscular dystrophy, with a 14 kilobase messenger RNA. Here we developed a new method for expressing large dystrophins by utilizing the protein trans-splicing mechanism mediated by split inteins. We identified several split intein pairs that efficiently join two or three fragments to generate a large midi-dystrophin or the full-length protein. We show that delivery of two or three AAVs into dystrophic mice results in robust expression of large dystroph

SUBMITTER: Tasfaout H 

PROVIDER: S-EPMC11335042 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature