Improved gene editing system delivered by a single virus to fix disease in mice

Effective gene knockout and base editing were achieved in mouse embryos using IscB-derived systems.

• IscBs, derived from Cas9 nuclease, are suitable for gene editing via single adeno-associated virus delivery.
• Natural IscBs show low activity in eukaryotic cells, prompting efforts to enhance their efficiency through protein engineering.
• An engineered variant of ωRNA, termed ωRNA-v2, was identified to improve gene editing efficiency.
• The engineered IscB-ωRNA system demonstrated robust capabilities for gene knockout and base editing in vivo.
• Single AAV delivery of IscB-derived base editors successfully corrected a disease in a mouse model of tyrosinemia.

Simplified