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Prime Editing Tool PERT Debuts as Broad, One-Time Strategy for Nonsense Mutations

The method equips cells with a permanent readthrough tRNA, pointing to a one-time therapy paradigm.

Overview

  • Scientists report PERT in Nature, using prime editing to convert a redundant human tRNA into a leucine suppressor that enables readthrough of premature stop codons.
  • In human cell models of Batten disease, Tay–Sachs disease, and Niemann–Pick C1, the approach restored enzyme activity to roughly 20–70% of normal.
  • In a Hurler syndrome mouse model, tissues showed about 6% average enzyme restoration with reported ranges of 0.3–10%, accompanied by improved pathology.
  • Across reported assays, investigators detected no off-target edits, no measurable disruptions to typical RNA or protein synthesis, and no cellular toxicity.
  • Nonsense variants account for about 24% of pathogenic mutations, yet current work installs only a leucine suppressor and broader coverage may require up to 19 engineered tRNAs, with further optimization and animal testing underway toward a future trial.