In vivo crispr editing of haematopoietic stem cells to model blood cancer progression

Abstract

JAK2V617F is the most common recurrent genetic abnormality found in myeloproliferative neoplasms (MPN). DNMT3A mutations are found in the methyltransferase domain and cluster around arginine 882 (e.g., R882H), particularly in advanced MPN, resulting in loss of DNA binding and reduced catalytic activity. We used CRISPR-Cas9 gene editing technology to edit Dnmt3a function in transgenic Jak2V617F murine HSPC.