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**1. Introduction** 

**4** 

**Bioreducible Cationic Polymers** 

*The Institute for Advanced Materials and Nanobiomedicine* 

Gene therapy holds substantial promise for the treatment of a broad class of overwhelming human diseases such as cancer and AIDS (Verma & Somia, 1997). An essential procedure in gene therapy program involves the delivery of encoded plasmid genes into the patient's somatic cells so as to express therapeutic proteins. An ideal strategy for successful gene delivery depends on safe and efficient gene delivery vectors (El-Aneed, 2004). Generally, gene delivery vectors are classified into two categories: viral vectors and non-viral vectors. Viral vectors are derived from natural viruses such as adenovirus and retrovirus with eliminated pathogenicity. Because of their unique capability in cell infection, viral vectors are most popular for gene delivery *in vitro* and *in vivo*. Unfortunately, clinical practice of viral vectors is seriously hampered by a few inherent issues including random insertion into the host genomes, immunogenicity, gene-carrying capacity limitation, and small-scale production (C.E. Thomas et al., 2003). In the past decades, these safety concerns on viral vectors have led to accelerated advancement in non-viral vectors (S. Li & Huang, 2000). Non-viral vectors such as lipids and polymers take more advantages over conventional viral vectors, including low immunogenicity after repeated administration, easy manufacture, large-scale production and low cost. However, current non-viral systems typically fail to give rise to as efficient gene transfection as powerful viral vectors (Pack et al., 2005). Thus, the availability of highly potent non-viral gene delivery vectors still remains a big challenge. Among different non-viral vectors, cationic polymers have received much attention because they can be prepared by different polymerization methods and easily modified to introduce different bio-functional groups (Luo & Saltzman, 2000). In the past two decades, a few traditional cationic polymers such as chitosan, polyethylenimine (pEI), poly(L-lysine) (pLL), polyamidoamine (PAMAM) dendrimer (Figure 1) have been studied widely as non-viral vectors for gene delivery (de Smedt et al., 2000). These cationic polymers can self-assemble with negatively-charged genes to form polymer/gene complexes (polyplexes) and induce detectable gene transfection efficiency *in vitro*. However, these first-generation polymeric gene vectors are not yet applied further for clinical practice, mainly due to low transfection efficiency and/or high cytotoxicity (Anwer et al., 2003; Merdan et al., 2002). In the past few years, extra- and intracellular gene delivery barriers have been identified that may seriously

**for Gene Transfection** 

*Tongji University School of Medicine* 

Chao Lin and Bo Lou

*Tongji University, Shanghai* 

*P.R. China* 

