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Carboxymethyl chitosan prolongs adenovirus‐mediated expression of IL ‐10 and ameliorates hepatic fibrosis in a mouse model

2022; Wiley; Volume: 7; Issue: 3 Linguagem: Inglês

10.1002/btm2.10306

2380-6761

Yannian Gou, Yaguang Weng, Qian Chen, Jinghong Wu, Hao Wang, Jiamin Zhong, Yang Bi, Daigui Cao, Piao Zhao, Xiangyu Dong, Meichun Guo, William Wagstaff, Bryce Hendren‐Santiago, Connie Chen, Andrew Youssef, Rex C. Haydon, Hue H. Luu, Russell R. Reid, Le Shen, Tong‐Chuan He, Jiaming Fan,

Pancreatic function and diabetes

Effective and safe liver-directed gene therapy has great promise in treating a broad range of liver diseases. 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-microbial, inexpensive, and easy accessible. Here, by exploiting its biocompatibility, controlled release capability and anti-inflammatory activity, we investigated whether CMC can overcome the shortcomings of Ad-mediated gene delivery, hence improving the prospect of Ad applications in gene therapy. We demonstrated that in the presence of optimal concentrations of CMC, Ad-mediated transgene expression lasted up to 50 days after subcutaneous injection, and at least 7 days after intrahepatic injection. Histologic evaluation and immunohistochemical analysis revealed that CMC effectively alleviated Ad-induced host immune response. In our proof-of-principle experiment using the CCl