Peptide fusion improves prime editing efficiency.

Velimirovic, Minja; Zanetti, Larissa C; Shen, Max W; Fife, James D; Lin, Lin; Cha, Minsun; Akinci, Ersin; Barnum, Danielle et al. · Nat Commun · 2022

basic_science · Level V

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Abstract

Prime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, the Peptide Self-Editing sequencing assay (PepSEq), to measure how fusion of 12,000 85-amino acid peptides influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites. Top prime-enhancing peptides function by increasing translation efficiency and serve as broadly useful tools to improve prime editing efficiency.

Medical subject headings