Prime editing writes new DNA sequences without cutting both strands
Researchers described a genome editing method called prime editing in Nature. It pairs a catalytically impaired Cas9 endonuclease with an engineered reverse transcriptase and a prime editing guide RNA, which specifies the target site and encodes the edit. The system writes new genetic information directly into DNA, without double-strand breaks or donor DNA templates. The team performed more than 175 edits in human cells, including targeted insertions, deletions, and all 12 types of point mutation. They corrected the primary genetic causes of sickle cell disease and Tay-Sachs disease, installed a protective mutation in PRNP, and inserted tags and epitopes into target loci. Four human cell lines and primary post-mitotic mouse cortical neurons supported prime editing, though efficiency varied. Compared with homology-directed repair, prime editing showed higher or similar efficiency with fewer byproducts, and it produced much lower off-target editing than Cas9 nuclease at known Cas9 off-target sites.
The researchers estimate prime editing could in principle correct up to 89% of known genetic variants linked to human disease, well beyond what earlier editing methods could reach.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].