PE3max

PE3max is an optimized prime editing system designed for high-efficiency genome editing in primary cells, including hematopoietic stem and progenitor cells (HSPCs). Prime editing is a search-and-replace technology that uses a fusion protein consisting of a catalytically impaired Cas9 endonuclease (nickase) and an engineered reverse transcriptase, guided by a prime editing guide RNA (pegRNA). The PE3 system specifically utilizes an additional sgRNA to nick the non-edited DNA strand, which stimulates DNA repair and significantly increases editing efficiency compared to the PE2 system. The max designation refers to architectural optimizations, such as human codon optimization and the addition of multiple nuclear localization signals (NLS), to enhance expression and nuclear import. PE3max has demonstrated potential in correcting pathogenic mutations, such as the HBB-E6V mutation causative of sickle cell disease, particularly when combined with strategies to modulate nucleotide metabolism.

Other names

prime editing system 3 max