Synthetic vectors

Formation of a complex between DNA and polycationic compounds appears to be the initial and quite possibly a critical parameter for nonviral gene delivery. Several synthetic vector systems, which are generally cationic in nature, including poly(lysines), cationic liposomes or various types of block copolymers and recently dendrimers, have been shown to self-assemble with plasmid DNA [13-15] [16]. Specific physicochemical properties manifested by these DNA complexes depend on the type of cationic agent used however, interesting patterns for such interactions are beginning to evolve [17, 18]. Under certain conditions, the interaction of DNA with polyvalent cations results in... 

Peptides have many desirable properties as components of synthetic vectors. Peptide synthetic chemistry is well established, with the convenience of automated synthesis resulting in a well-defined, high-purity product of low toxicity and immunogenicity for in vivo use. Furthermore, even short peptides of 7 to 30 amino acids can accommodate enormous structural diversity, functionality, and combinations of properties. 

Parkes R, Meng QH, Siapati KE, et al. High efficiency transfection of porcine vascular cells in vitro with a synthetic vector system. J Gene Med 2002 4(3) 292-299. 

Uduehi A, Mailhos C, Truman H, et al. Enhancement of integrin-mediated transfection of haematopoietic cells with a synthetic vector system. Biotechnol Appl Biochem 2003 38(Pt 3) 201-209. 

Polymer-based biomaterials are becoming increasingly important, whether they are used as medical supplies (pipes, catheters, bags), prostheses, or dental materials, or in a pharmaceutical context as drug conjugates [4, 7, 158-160], protein conjugates [6, 158, 159, 161], synthetic vectors [12, 14, 18, 162, 163], or as immuno-adjuvants [164, 165]. 

Alio, J.-C., Midoux, P., Merten, M., Souil, E., Lipecka, J., Figarella, C. et al. (2000) Efficient gene transfer into human normal and cystic fibrosis tracheal gland serous cells with synthetic vectors. Am. J. Res. Cell Mol. Biol., 22, 166-175. 

Read ML, Logan A, Seymour LW (2005) Barriers to gene delivery using synthetic vectors. Adv Genet 53PA 19 16... 

Table 21.3 shows the clinical studies that have been conducted worldwide, with their different applications, showing that therapies intended for monogenic disease treatment are the second most assessed group, after therapies for tumor treatment. The most used vectors in gene therapy clinical studies are viral vectors (68%), and among those, retroviruses and adenoviruses are the viruses of choice. Synthetic vectors were used in 25% of the studies performed, and about 16% correspond to the use of naked plasmid DNA (Table 21.4). 

Nonviral Vectors. The existing synthetic vectors (naked DNA, cationic liposomes, etc.) are far from being perfect delivery systems. Although they are less pathogenic and may have reduced toxicity compared with some existing viral vectors, depending on the dose injected, liposomes may aggregate in the blood and can cause severe toxic reactions [6]. 

Biological Targeting. Biological vector targeting uses modification of viral coat proteins (for viral vectors) or surface properties of synthetic vectors (e.g., liposomes). 

It is essential to study the biodistribution of components involved in gene transfer (virus, synthetic vector, or nucleic acid) to identify all in vivo barriers. This study indicates what proportion of the administered dose actually reaches the target, as well as any unexpected localizations (according to the quantity at each site) or blocking sites, which is of particular interest because it allows prediction of the... 

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