Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors
Key Finding
Developed compact adenine base editors (SaABE8e, SaKKH-ABE8e, Nme2ABE8e, CjABE8e, SauriABE8e) that fit in single AAV vectors and outperform dual-AAV split-intein systems. Single-AAV delivery achieved 2.5-fold higher editing efficiency than dual-AAV at matched doses, with 66% liver, 33% heart, and 22% muscle editing. Demonstrated therapeutic efficacy with 93% knockdown of PCSK9/Pcsk9/Angptl3 and substantial reductions in plasma cholesterol and triglycerides. Three size-minimized ABE8e variants collectively enable targeting of ~82% of genomic adenines.