Therapeutic adenine base editing of human hematopoietic stem cells

In this paper, we confirmed for the first time that ABE8e-sgRNA RNP complex can achieve efficient multiplex editing in both healthy and beta-thalassemia human HSPCs. After strict detection by deep sequencing, no harmful off-target editing was found. Comparing mRNA and RNP delivery methods, we found that RNP delivery significantly reduced gRNA-dependent DNA off-targeting without compromising editing efficiency. Notably, we successfully repaired two causative mutations in situ using ABE8e-SpRY, providing support for the use of ABE to treat other genetic diseases. Stored here are deep sequencing files for editing efficiency tests at both on-target and off-target sites after editing.