cas12a ribonucleoproteins

Cas12a ribonucleoproteins (RNPs) represent an allele-selective genome editing strategy designed for the precise inactivation of oncogenic driver mutations, specifically the JAK2V617F mutation found in myeloproliferative neoplasms (MPNs). This approach exploits the fact that the G>T point mutation in JAK2V617F creates a *de novo* target site for the Cas12a nuclease. By electroporating Cas12a RNPs into CD34+ cells from MPN patients, the strategy achieves high inactivation rates of V617F alleles (97%) with minimal targeting of wild-type alleles (<3%). The editing reverts aberrant transcriptional phenotypes in heterozygous cells and leads to loss of viability in homozygous mutant cells, while maintaining the colony-forming ability and multilineage differentiation potential of edited CD34+ cells. *In vivo* xenotransplantation models demonstrated increased overall survival and reversal of disease phenotypes, providing a proof of concept for its therapeutic potential.

Other names

Cas12a RNPsCas-12a RNPsCas 12a RNPs