sgRNA amount is a limiting factor in adenine base editing using RNA LNPs

tissue analysis, and sequencing. Increasing the guide RNA dose to 4 mg/kg enhanced editing efficiency up to 3.3-fold in multiple tissues compared to the standard 1 mg/kg dose, with the liver exhibiting the highest on-target editing rates at 63%. Bystander editing increased significantly with higher guide RNA doses, particularly in highly edited tissues like the liver, where bystander edits showed a dose-dependent increase. These findings demonstrate the importance of careful guide RNA dose optimization to balance editing efficiency and tissue specificity with bystander effects in the therapeutic applications of ABE8e.