Cas12a RNP-based JAK2 V617F gene editing therapy

Cas12a RNP-based JAK2 V617F gene editing therapy is an experimental CRISPR-based ex vivo cell therapy being developed by researchers at the University of Oxford for the treatment of myeloproliferative neoplasms (MPNs). The therapy utilizes Cas12a Ultra ribonucleoproteins (RNPs) delivered via electroporation into patient-derived CD34+ hematopoietic stem cells. By exploiting a de novo protospacer adjacent motif (PAM) created specifically by the V617F G>T point mutation, the Cas12a nuclease selectively targets and inactivates the oncogenic JAK2 allele while sparing the wild-type version. This allele-selective approach aims to reduce the variant allele frequency (VAF) and eliminate the malignant clone while maintaining healthy hematopoiesis. Preclinical studies have demonstrated that this therapy can revert aberrant transcriptional phenotypes and improve survival and disease hallmarks in animal models, supporting its development as a potential autologous transplant-based treatment.

Other names

Cas12a ribonucleoprotein-based therapyCas-12a ribonucleoprotein-based therapyCas 12a ribonucleoprotein-based therapyJAK2 V617F CRISPR therapyJAK-2 V617F CRISPR therapyJAK 2 V617F CRISPR therapyCas12a-RNP edited CD34+ cells