Abstract Prime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, PepSEq, to measure how fusion of 12,000 85-amino acid peptides derived from human DNA repair-related proteins 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.

Peptide fusion improves prime editing efficiency