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Progress and Prospects of Chitosan and Its Derivatives as Non-Viral Gene Vectors in Gene Therapy

[ Vol. 9 , Issue. 6 ]

Author(s):

Haijun Tong, Qin Shi, Julio C. Fernandes, Li Liu, Kerong Dai and Xiaoling Zhang   Pages 495 - 502 ( 8 )

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 nonviral 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.

Keywords:

Chemical modification, biological reconstruction, rate-limiting step, chitosan/siRNA complex

Affiliation:

Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM)&Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), 225 South Chongqing Road, Shanghai 200025, China.



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