RP1 Dual-AAV Gene Therapy Preserves Retinal Structure and Ameliorates Photoreceptor Degeneration in a Murine Model of Retinitis Pigmentosa.

ABSTRACT:

Purpose

This study aimed to develop and compare dual-adeno-associated virus (AAV) gene therapy utilizing protein trans-splicing versus mRNA trans-splicing to restore RP1 expression, and to evaluate their safety and efficacy in rescuing photoreceptor degeneration in a mouse model of RP1-associated retinitis pigmentosa (RP).

Methods

By screening various split sites within the RP1 sequence in combination with different inteins or adopting mRNA trans-splicing binding sequences, we generated several plasmid pairs capable of reconstituting RP1 in vitro. Next, we conducted dual-AAV gene therapy via subretinal injection in RP1-/- mice. We validated the RP1 protein reconstitution in vivo by Western blotting. To assess the safety and efficacy of dual-AAV systems in RP1-/- mice, retina

SUBMITTER: Liu F 

PROVIDER: S-EPMC12439500 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature