First demonstration of SaCas9 for single-AAV in vivo genome editing. Achieved >40% indel frequency in mouse liver targeting Pcsk9. Established SaCas9 as viable alternative to SpCas9 for gene therapy.
In vivo genome editing using Staphylococcus aureus Cas9
SpCas9's size limited AAV packaging for in vivo editing, and alternatives like St1Cas9 had drawbacks. This paper found S. aureus Cas9 (SaCas9), over 1 kb shorter than SpCas9, matching its efficiency. AAV8-delivered SaCas9 targeting Pcsk9 cut serum Pcsk9 by 95% in mice.