Chemical modification of chitosan as a gene carrier in vitro and in vivo

Currently, the success of gene therapy is mainly limited due to the lack of effective vector systems. Although viral vectors are highly efficient in transfecting cells, undesirable complications limit their therapeutic applications. Chitosan has been investigated as a non-viral vector offering several advantages, such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, the low transfection efficiency and low cell specificity of chitosan as a DNA carrier need to be overcome before undertaking clinical trials. The objective of this review is to summarize the use of chitosan and chitosan derivatives in gene therapy, and particularly the role of several factors for the enhancement of transfection efficiency and cell specificity in vitro, such as the degree of deacetylation and molecular weight of chitosan, pH, serum, charge ratio of chitosan to DNA and cell type on transfection efficiency, chemical modification. The administration of the chitosan derivative formulations in vivo is also included, and, the role of chitosan as a carrier of controlled release of DNA and small interfering RNA is described.