Peptide fusion improves prime editing efficiency
Minja Velimirovic, Larissa C. Zanetti, Max W. Shen, James D. Fife, Lin Lin, Minsun Cha, Ersin Akıncı, Danielle Barnum, Tian Yu, Richard I. Sherwood
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.