dabe8e

dABE8e is a nickase-deficient adenine base editor (ABE) derived from the ABE8e system. It is engineered to perform precise adenine-to-guanine (A-to-G) transitions in genomic DNA without inducing the double-strand breaks or significant insertions/deletions (InDels) typically associated with standard CRISPR-Cas9 or nickase-active base editors. In the context of hemoglobinopathies, dABE8e is utilized to edit transcription factor binding sites within the HBG1 and HBG2 promoters (such as the -175 TAL1 site or -123/-124 KLF1 site) to induce fetal hemoglobin (HbF) production. By using a nickase-deficient architecture, dABE8e minimizes large deletions and unintended genomic modifications, making it a potentially safer tool for the treatment of sickle cell disease and β-thalassemia.