Prime editing-installed suppressor tRNAs for disease-agnostic genome editing.

ABSTRACT: Precise genome-editing technologies such as base editing^1,2 and prime editing³ can correct most pathogenic gene variants, but their widespread clinical application is impeded by the need to develop new therapeutic agents for each mutation. For diseases that are caused by premature stop codons, suppressor tRNAs (sup-tRNAs) offer a more general strategy. Existing approaches to use sup-tRNAs therapeutically, however, require lifelong administration^4,5 or show modest potency, necessitating potentially toxic overexpression. Here we present prime editing-mediated readthrough of premature termination codons (PERT), a strategy to rescue nonsense mutations in a disease-agnostic manner by using prime editing to permanently convert a dispensable endogenous tRNA into a

SUBMITTER: Pierce SE 

PROVIDER: S-EPMC12675287 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature