title: Progress and prospects of chitosan and its derivatives as non-viral gene vectors in gene therapy.
abstract: Although cell transfection by viral vectors is highly efficient, undesirable side effects including immunogenicity, toxicity and carcinogenesis have to be taken into consideration before their clinical applications. In contrast, most non-viral vectors, such as chitosan, are advantageous due to their biocompatibility, biodegradability, low toxicity and immunogenicity. However, the tranfection efficiency of chitosan as gene vector is rather low because of its low stability and low buffering capacity. Recent technological progress in chemical modification of chitosan has led to improvements of its transfection efficiency without disturbing its biocompatibility and biodegradability. These advances have led to a better understanding of the relationship between the physicochemical characteristics of a non-viral vector and its transfection efficiency. In this review, we summarize the obstacles encountered during the transfection process of chitosan and its derivatives, and then focus on strategies to overcome these obstacles. An accurate method for determining the rate-limiting step and intracellular unpacking kinetics of chitosan and its derivatives is also presented. Lastly, gene-silencing chitosan/small interfering RNA (chitosan/siRNA) complexes and prospects of feasible methods for enhancing the transfection efficiency of chitosan and its derivatives are discussed.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tong
authors.forename: Shi
authors.initials: S
authors.lastname: Qin
authors.forename: Julio C
authors.initials: JC
authors.lastname: Fernandes
authors.forename: Liu
authors.initials: L
authors.lastname: Li
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001672:Biocompatible Materials; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007700:Kinetics; D034741:RNA, Small Interfering
chemical_list: D001672:Biocompatible Materials; D034741:RNA, Small Interfering; D004247:DNA; D048271:Chitosan