AAV-delivered engineered suppressor tRNA rescues visual function in mice with an inherited retinal disease.

ABSTRACT: Nonsense mutations change a sense codon into a premature termination codon (PTC) in mRNA and account for approximately 18.5% of human inherited retinal diseases (IRDs)-related mutation. Nonsense suppression therapies by small molecular drugs or suppressor tRNAs (sup-tRNAs) can introduce an amino acid at PTC, thereby promoting the production of full-length proteins. While sup-tRNA-based therapies have shown promising results in cell culture models, challenges remain for in vivo delivery, particularly regarding efficacy, stability, and safety. In this study, we engineer the body sequence of sup-tRNA^Arg to enhance readthrough efficiency at clinically relevant PTCs in the RPE65 and ABCA4 genes. By using the self-complementary adeno-associated virus (scAAV), we achieve restoration of

SUBMITTER: Ren C 

PROVIDER: S-EPMC12712100 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature