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**19** 

**Chitosan-DNA/siRNA** 

 *Université de Montréal* 

*Paulista- Brazil* 

*1Canada 2Brazil 3China* 

**Nanoparticles for Gene Therapy** 

Mohamed Benderdour1 and Julio C. Fernandes1

Qin Shi1, Marcio J. Tiera2, Xiaoling Zhang3, Kerong Dai3,

*1Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal* 

*3The 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)* 

*2Departamento de Quimica e Ciencias Ambientais, UNESP-Universidade Estadual* 

Human diseases can be treated by the transfer of therapeutic genes (transgene) into specific cells or tissues of patients to correct or supplement defective, causative genes. Gene therapy offers a solution to controlled and specific delivery of genetic materials (DNA and RNA) to targeted cells. The success of gene therapy depends on the ability to deliver these therapeutic materials to targeted site. Viral vectors (e.g. adenovirus) are very effective in term of transfection efficiency, but they have limitations *in vivo*, particularly by their safety concern and non tissue-specific transfection. Non-viral gene transfer systems are limited by their lower gene transfer efficiency, low tissue specificity and transient gene expression. Chitosan is a polysaccharide usually obtained from deacetylation of chitin, which may be extracted from various sources, particularly from exoskeletons of arthropods such as crustaceans. The goal of this chapter is to introduce the readers to chitosan as a DNA/small interfering RNA (siRNA) delivery vector, as well as different variable strategies to improve cellular transfection and its potential clinical application. the first section is to present of chapter (section 1). The second section presents the discussion about barriers to DNA/siRNA delivery *in vitro* and *in vivo*. It is important to have a clear overview of obstacles to the *in vivo* treatment with DNA/siRNAs. Different *in vivo* administration routes will encounter different physiological barriers, and complications may be furthered by different cells in organs and tissues (section 2). The third section provides the readers with an understanding of the key steps of cellular internalization of DNA/siRNA non-viral vectors. Internalization of non-viral vector-based DNA/siRNA delivery system into cells typically occurs through endocytosis (section 3). the fourth section describes chitosan as a vector for gene therapy (section 4) followed by chitosan structure and physicochemical

**1. Introduction** 

