NAs [nucleoside analogs] have been well tolerated and have served as the standard of care for CHB [chronic HBV] for decades. To evaluate the efficacy of [the client's] anti-HBV gene-editing product in combination with an NA, AAV-HBV mice were treated with entecavir (ETV) via drinking water for 2 weeks (days 0–14) and were dosed with LNPs encapsulating SaCas9-encoding mRNA and the pair of the HBV-targeting gRNAs on days 0 and 14. No clinical signs of distress, pain, and overall health were observed following LNP administration. As expected, ETV treatment produced little change in HBsAg levels, whereas HBsAg reduction increased in a dose-dependent manner with LNP administration (Figures 7A and 7B). Up to 3 weeks after the start of the treatment (day 21), serum HBV DNA levels continued to decrease in all ETV-treated groups, relative to those receiving LNPs alone (Figures 7C and 7D). The intracellular concentration of ETV seemed to be high enough to block reverse transcription for up to 7 days after 2 weeks of ETV treatment. HBV DNA levels then rebounded in the ETV-only group but remained suppressed in mice receiving both ETV and LNPs. These results suggest that the combination therapy may control viral load more effectively than either monotherapy.