Non-viral DNA vectors

ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY 

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Kneuer, C., Sameti, M., Bakowsky, U., Schiestel, T., Schirra, H., Schmidt, H., and Lehr, C.M., Surface modified silica-nanoparticles can enhance transfection in vitro a novel class of non-viral DNA vectors, Bioconjugate Chemistry, 2000, 11, 926-932. 

Another possible method of endosome escape is the proton-sponge hypothesis [74]. Non viral DNA vectors that are able to accept protons at physiological pHs, such as polyethylenimine (PEI), act as a buffering agent within endosomes. As a result, more protons are pumped into the endosome, accompanied by an influx of chloride ions (to maintain the appropriate membrane potential) and water (due to osmotic pressure), which may lead to endosome rupture. 

Ward C M (2000). Folate-targeted non-viral DNA vectors for cancer gene therapy. Curr. Opin. Mol. Ther. 2 182-187. 

J. Wu, D. Yamanoucfai, B. Liu, C.C. Chu, Biodegradable aiginine-based poly(edia ester amide)s as a non-viral DNA delivCTy vector and their structuie-dunction study, J. Mater. Chem. 22 (2012) 18983-18991. 

Wu J, Yamanouchi D, Liu B, Chu C. Biodegradable arginine-based poly(ether ester amide)s as a non-viral DNA delivery vector and their structure-function study. J Mater Chem 2012 22(36) 18983-91. 

Fig. 1.11 Applications of LDHs as (A) non-viral vector in gene therapy for transfection of DNA to the cell nucleus, and (B) as matrix for enzymes immobilization in the development of biosensors.

Theoretically, this appears to be a htting solution to gene problems. However, there are problems, such as immune and inflammation responses, toxicity, and means to target the intended cells. Non viral vectors may overcome the problems with viral delivery agents. Lipids, in the form of liposomes and other lipid complexes, are being studied. Injection of DNA directly into a patient s muscle cells is another avenue being researched. 

Hebert E. Improvement of exogenous DNA nuclear importation by nuclear localization signal-bearing vectors a promising way for non-viral gene therapy Biol Cell 2003 2 95(2) 59-68. 

Fischer, D., Bieber, T., Li, Y., Elsasser, H-P, Kissel, T. (1999). A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine effect of molecular weight on transfection efficiency and cytotoxicity. Pharm. Res., 16, 1273-12791. 

Read, M.L., Etrych, T., Ulbrich, K., Seymour, L.W. (1999). Characterisation of the binding interaction between poly(L-lysine) and DNA using the fluorescamine assay in the preparation of non-viral gene delivery vectors. FEBS Lett., 461(1-2), 96-100. 

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. 

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