To develop a broadly applicable genome editing vector for OTCD, we constructed a new AAV8 donor vector that contains (i) an sgRNA driven by the U6 promoter to target intron 4 of the mOTC locus (25) and (ii) a fully functional minigene expressing codon-optimized human OTC (hOTCco) driven by a liver-specific thyroxine binding globulin (TBG) promoter (TBG.hOTCco.pA) flanked by 0.9-kb homology arms on each side (referred to as AAV8.targeted donor; Fig. 1). Here, OTC is linked to ornithine carbamoyltransferase deficiency.