Engineered tRNAs suppress nonsense mutations in cells and in vivo.

ABSTRACT: Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases¹. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation^2-7. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs into  efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properti

SUBMITTER: Albers S 

PROVIDER: S-EPMC10284701 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature