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While adenoviral (Ad) vectors have been widely used for efficacious in vivo gene delivery, their translational utilities are severely limited due to the short duration of transgene expression and solicitation of host immune response. Used as a promising polymeric vehicle for drug release and nucleic acid delivery, carboxymethyl chitosan (CMC) is biocompatible, biodegradable, anti\u2010microbial, inexpensive, and easy accessible. Here, by exploiting its biocompatibility, controlled release capability and anti\u2010inflammatory activity, we investigated whether CMC can overcome the shortcomings of Ad\u2010mediated gene delivery, hence improving the prospect of Ad applications in gene therapy. We demonstrated that in the presence of optimal concentrations of CMC, Ad\u2010mediated transgene expression lasted up to 50\u2009days after subcutaneous injection, and at least 7\u2009days after intrahepatic injection. Histologic evaluation and immunohistochemical analysis revealed that CMC effectively alleviated Ad\u2010induced host immune response. In our proof\u2010of\u2010principle experiment using the CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced experimental mouse model of chronic liver damage, we demonstrated that repeated intrahepatic administrations of Ad\u2010IL10 mixed with CMC effectively mitigated the development of hepatic fibrosis. Collectively, these results indicate that CMC can improve the prospect of Ad\u2010mediated gene therapy by diminishing the host immune response while allowing readministration and sustained transgene expression.\n                  <\/jats:p>","DOI":"10.1002\/btm2.10306","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T07:50:45Z","timestamp":1646293845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Carboxymethyl chitosan prolongs adenovirus\u2010mediated expression of\n                    <scp>IL<\/scp>\n                    \u201010 and ameliorates hepatic fibrosis in a mouse model"],"prefix":"10.1002","volume":"7","author":[{"given":"Yannian","family":"Gou","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory of Diagnostic Medicine, and Department of Clinical Biochemistry, School of Laboratory Medicine Chongqing Medical University  Chongqing 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