A Novel AAV Capsid-Mediated RS1 Gene Therapy Restored Retinal Function to Wild-Type Levels in Rs1R213W Mouse Model.

ABSTRACT:

Purpose

X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by retinoschisin 1 (RS1) gene variants, potentially leading to severe visual impairment and blindness. This study aimed to develop a novel adeno-associated virus (AAV) serotype and evaluate its therapeutic potential in an XLRS mouse model.

Methods

A novel RS1 mouse model was established using the CRISPR-Cas9 gene editing system and underwent phenotypic characterization. AAV.IVT18-scRS/CMV-RS1, comprising a rationally designed novel capsid (AAV.IVT18) and an optimized RS1 gene expression cassette, was then constructed and delivered via intravitreal injection into mutant and wild-type (WT) mice at 3 to 4 weeks of age. Retinal structure, function, and inflammation levels were evaluated after treatment.

SUBMITTER: Wei X 

PROVIDER: S-EPMC12007669 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature