Fig. 6.

Off-target analysis and vector toxicity show little long-term consequences of gene knock-in. a Computationally derived top off-target candidate sites (Syn3, Ano6, Nft3, and chr5: 46645544) were submitted to targeted Illumina deep sequencing for evidence of NHEJ activity based upon indel formation following imperfect DNA repair. Amount of virus administered had no effect on the presence of indel formation at the selected candidate off-target sites. Each dot represents data from one individual mouse. b Mice were submitted in a blinded manner to gross pathology examination with an emphasis on liver toxicity markers (ALT/AST transaminases) and whole blood cell counts levels, 7 months after receiving hAAT-encoding vectors. Each dot represents data from one mouse. Error bars are s.d. of the mean. hAAT donor is Ad5-EF1α-hAAT and GFP sham is Ad5-CMV-EGFP. WBC white blood count, RBC red blood count, HGB hemoglobin, MCH mean cell hemoglobin