Viral carriers

No matter what their composition, such synthetic gene delivery systems also meet various biological barriers to efficient cellular gene delivery. Viral vector-based systems are far less prone to such problems, as the viral carrier has evolved in nature to overcome such obstacles. Obstacles relate to ... 

The main invasive pathogens are bacteria and viruses and recombinant live carriers using bacterial and viruses have been described. Viral carriers rely on the established and efficient methods for invading and infecting eukaryotic cells and their in vivo replicative process improves the induction of type I and type II immune responses. 

Gene therapy using viral carriers would appear to be at a crossroad at the present time, although other options for gene delivery to cells require exploration and evaluation. The optimism of a generation ago is being replaced by cautious exploration. 

Compared to viral vectors, the potential advantages of synthetic carriers (also called non-viral vectors) are apparent. Being synthetic, they could be made safe, non-immunogenic, easy to prepare and cost-effective. DNA delivered by these carriers may not be able to replicate or recombine into infectious forms. Among many reported non-viral carriers, including cationic polymers (Behr et al., 1989 Kukowska-Latallo et al., 1996 Wu and Wu, 1988) and cationic lipids (Feigner, 1990 Lee and Huang, 1997), the most frequently used form is cationic liposomes. 

Karmali PP, Chaudhuri A (2007) Cationic liposomes as non-viral carriers of gene medicines resolved issues, open questions, and future promises. Med Res Rev 27 696-722... 

As previously discussed, the protection of pDNA against degrading enzymes is a critical parameter for a non-viral carrier. Such ability is needed for the polyplex to protect the nucleic acid for an extended period of time in the blood while the polyplex circulates and distributes. Research conducted in 1999 by Richardson and coworkers [101] to study the ability of chitosan to protect against DNase degradation revealed that incubation of polyplexes prepared at NIP ratio of 3/1 in the presence of DNase I (8 U, 1 h incubation) protected pDNA from degradation. Other studies of chitosans as gene delivery vehicles confirm that the NIP ratio has to be at least 3/1 to 5/1 in order to provide a sufficient protective effect against DNases. 

Synthetic pathways that supposedly avoid the pitfalls of viral delivery systems (see below) have been explored. Both Kaneda and coworkers (Chapter 9) and Sorgi and coworkers (Chapter 8) have been successful in designing viruslike liposomal delivery systems that provide some of the advantages of viral carriers—in other words, cell surface recognition and fusion with target cells (or intracellular compartments, i.e., endosomes, respectively)—without the detrimental immune response that viral systems generate. The efficiency of these systems is still orders of magnitude less than that of viral carriers however, cytotoxic... 

Brown MD, Schatzlein AG, Uchegbu IF (2001), Gene delivery with synthetic (non-viral) carriers, Int. J. Pharm. 229 1-21. 

Luten J, Van Nostrum C, De Smedt S, Hennink W (2008) Biodegradable polymers as non-viral carriers for plasmid DNA delivery. I Control Release 126 97-110... 

The nonviral gene transfection systems introduced in recent years bear significant advantages over the viral systems that will not be discussed here. For reviews of viral carrier systems, those by Sandrin et al. [33] and Schweizer et al. [34] are recommended (see also Part I, Chapter 6). One fact in favor of nonviral carriers is that many such systems are aheady well established in classical areas of pharmaceutical technology. Their production methods have already been optimized and safety as-... 

Nanoparticles fabricated from PGA have also shown some tremendous promise as viral carriers for tumor vaccines. Earlier studies have shown that they can deliver antigens at significantly higher amounts to antigen-presenting cells as controls. Enhanced downstream effect and increased immune response were observed in antigen-specific cytotoxic T lymphocytes [264-266]. Similar nanoparticles have been synthesized with PGA in the backbone [267]. The surface charge and the hydrophilicity of the PGA are some of the characteristics that have been exploited in such... 

Other Cationic Polymer-Based Non-viral Carriers... 

Chan, P., Kurisawa, M., Chung, J. E., and Yang, Y. Y. 2007. Synthesis and characterization of chitosan-g-poly(ethylene glycol)-folate as a non-viral carrier for tumor-targeted gene delivery. Biomateriab 28 540-549. 

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