Gene therapy has been considered to be the promising and accomplishing approach to counter persistent HBV infection and primary hepatocellular carcinoma (HCC).Replication-defective adenoviruses were one of the most potent vectors for targeted gene delivery.However,clinical application to the best-studied human adenovirus type-5 (AdHu5) is limited by the high prevalence of pre-existing neutralizing antibodies (NAb) due to natural infection,while rare Ad serotypes such as chimpanzee adenovirus type-68 (AdC68) and human adenovirus type-26 (AdHu26) could circumvent pre-existing immunity and serve as substitutes for AdHu5.