Disease Modeling Of Severe Congenital Neutropenia Using Crispr/Cas9 Gene Correction Or Knockout Of Elane In Patients Derived Induced Pluripotent Stem Cells

Severe congenital neutropenia (CN) is a monogenic bone marrow failure syndrome with the frequency of 1:200,000 and is characterized by an absolute neutrophil count below 500 cells per microliter. Patients with CN suffer from severe life-threatening bacterial infections starting early after birth due to the absent or very low numbers of neutrophils in peripheral blood. While CN is a heterogeneous disease caused by many different gene mutations, autosomal-dominant ELANE mutations are the most common cause of CN. Although the majority of CN patients respond to daily treatment with granulocyte colony-stimulating factor (G-CSF), approximately 15 % do not respond at doses up to 20 μg/kg/day and approximately 20 % of G-CSF treated patients develop myelodysplasia (MDS) or acute myeloid leukemia (AML).