ABE8e-NRCH

ABE8e-NRCH is an adenine base editor (ABE) designed for the treatment of sickle cell disease (SCD). It consists of an evolved adenine deaminase (ABE8e) fused to a Cas9 variant (NRCH) that possesses an expanded protospacer adjacent motif (PAM) recognition capability, allowing it to target the specific A-to-G mutation site in the HBB gene. The editor converts the pathogenic HBB S allele into the non-pathogenic HBB Makassar (HBB M) variant. This approach aims to provide a curative treatment by permanently correcting the genetic defect in hematopoietic stem and progenitor cells (HSPCs). Research has demonstrated high editing efficiency in both human CD34+ cells and non-human primate models, with potential for both ex vivo and in utero in vivo applications.