Scientists developed PERT (prime editing-mediated readthrough of premature termination codons), which converts normal cellular tRNAs into suppressor tRNAs that can read through premature stop codons. The technique screened 418 human tRNAs to identify optimal candidates, then used prime editing to permanently modify a single genomic locus without requiring gene overexpression. Testing in cell models of Batten disease, Tay-Sachs, and cystic fibrosis showed efficient protein rescue, while mouse studies of Hurler syndrome demonstrated substantial disease pathology reversal.
This represents a potential paradigm shift for treating genetic diseases caused by nonsense mutations, which account for roughly 11% of all genetic disorders. Unlike traditional approaches requiring lifelong drug administration or risky gene overexpression, PERT creates a permanent cellular modification with a single treatment. The disease-agnostic nature means one therapeutic platform could theoretically treat thousands of different genetic conditions sharing the same underlying mechanism. However, the approach faces significant hurdles including delivery to relevant tissues, potential off-target effects, and the challenge of achieving sufficient suppressor tRNA levels across different cell types. The safety profile appears promising with no detected readthrough of natural stop codons, though long-term effects remain unknown.
