Developed prime editing enabling all 12 base-to-base conversions plus insertions/deletions without DSBs or donor DNA. Fused reverse transcriptase to Cas9 nickase with prime editing guide RNA (pegRNA).
Search-and-replace genome editing without double-strand breaks or donor DNA
Base editors installed only transitions, and HDR needed DNA breaks plus donor DNA. Prime editing fuses a Cas9 nickase to reverse transcriptase, guided by a pegRNA, to rewrite DNA directly. PE3 corrected the sickle-cell HBB mutation at 58% efficiency.