Figure 5.

LNP-mediated delivery of base editor and HBV-targeting gRNAs leads to sustained reduction of viral markers in HBV minicircle mouse model

(A) Experimental scheme. (B) Seven weeks after the injection (day 0), mice injected with BE4/(g37 + g40) showed > 2log10 mean serum HBsAg reduction; 4/5 mice injected with HBV-specific LNPs showed HBsAg reduction below the limit of detection. (C) HBV replication is reduced in ETV-treated mice and then rebounds when the treatment is discontinued at day 14 (positive control). Base editing treated mice showed up to 3log10 sustained reduction in serum HBV DNA with no rebound observed. (D) Two weeks after the beginning of treatment, all mice treated with BE4/(g37 + g40) showed HBeAg below the limit of detection. (E) Total HBV DNA levels were assessed on the DNA purified from mice liver at the end of the experiment. (F) Editing was assessed on the DNA purified from mice liver by NGS. The data are represented as mean ± SEM, n = 4 or 5 mice per group.