Nature biotechnology

Designed pegRNAs increase the accuracy of prime editing

Updated

Abstract

Engineered pegRNAs (epegRNAs) improve prime editing efficiency by 3-4 times in various human cell types.

  • Prime editing allows for precise modifications in DNA, including point mutations and small insertions or deletions.
  • Degradation of specific regions of the pegRNA can diminish the effectiveness of prime editing.
  • Incorporating structured RNA motifs at the 3' end of pegRNAs enhances their stability and editing efficiency.
  • The modified pegRNAs maintain a low risk of off-target effects during DNA editing.
  • Optimized structural motifs and a new computational tool (pegLIT) were developed to improve pegRNA design.
  • epegRNAs facilitate the installation or correction of mutations associated with diseases.

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Funding

Competing interests

Competing Interests. The authors are co-inventors on patents filed by the Broad Institute on prime editing. D.R.L. is a consultant and co-founder of Prime Medicine, Beam Therapeutics, and Pairwise Plants, companies that use genome editing. A.V.A. is currently an employee of Prime Medicine.
PubMed

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