Nonviral vector

Direct application Viral vectors Nonviral vectors Naked nucleic acids... 

Presently, 1,260 gene-therapy trials are underway worldwide (Tables 1 and 2). For details see http // www.wiley.co.uk/genetherapy/clinical/. Almost three fourths of all trials are based on viral vectors. The vast majority of nonviral gene-therapy trials use naked/ plasmid DNA (18% of all gene-therapy trials). 

Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, Yamasaki Y, Koyama H, Kataoka K (2008) PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. J Am Chem Soc 130 6001-6009... 

Choy, J.H., Kwak, S.Y., Jeong, Y.J. and Park, J.S. (2000) Inorganic layered double hydroxides as nonviral vectors. Angewandte Chemie-Intemational Edition, 39, 4042-4045. 

Finsinger D, Remy JS, Erbacher P, Koch C, Plank C (2000) Protective copolymers for nonviral gene vectors synthesis, vector characterization and application in gene delivery. Gene Ther 7 1183-1192... 

Ohlfest, J.R., Freese, A.B., and Largaespada, D.A. 2005. Nonviral vectors for cancer gene therapy prospects for integrating vectors and combination therapies. Current Gene Therapy 5(6), 629-641. 

Organically modified silica nanoparticles a nonviral vector for in vivo gene delivery and expression in the brain, Proc. Natl. Acad. Sci. USA, 2005, 102, 11539. 

If the vector is changed, a full safety evaluation may be required. However, if the changes are minor compared to the structure of a fully evaluated vector, it is appropriate for safety to be addressed by bridging studies. For example, if there is only a minor change on one of the condensation peptides of a nonviral, selfassembling vector, then some simple bridging work, rather than a full evaluation, may be appropriate. 

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... 

Sequential hydroformylation/reductive amination of dendritic perallylated polyglycerols with various amines in a one-pot procedure to give dendritic polyamines in high yields (73-99%). Furthermore, the use of protected amines provides reactive core-shell-type architectures after deprotection. These soluble but membrane filterable multifunctional dendritic polyamines are of high interest as reagents in synthesis or as supports in homogeneous catalysis as well as nonviral vectors for DNA-transfection (Scheme 18) [65]. 

Liposome-Polycation-DNA A Nonviral Gene Vector Turned into a Potent Vaccine Carrier... 

Genes can be introduced by the application of naked DNA alone however, better efficiency is achieved when the DNA is incorporated into a delivery vector. These delivery vectors consist of viral, those utilizing modified virus particles for DNA delivery, and nonviral, for which various chemicals are used to aid DNA packaging and delivery. Viral vectors confer significantly better transfection efficiency than nonviral vectors however, recently the toxicity and oncogenic side effects of viral vectors have become a major concern (6). Nonviral vectors do not have such serious side effects but lack the efficiency (7). 

Hart SL, Arancibia-Carcamo CV, Wolfert MA, et al. Lipid-mediated enhancement of transfection by a nonviral integrin-targeting vector. Hum Gene Ther... 

Keller M, Harbottle RP, Perouzel E, et al. Nuclear localisation sequence tern-plated nonviral gene delivery vectors investigation of intracellular trafficking events of LMD and LD vector systems. Chembiochem 2003 4(4) 286-298. 

It should be emphasized at this point that the use of physicochemical methods is so far the only way to demonstrate the import of transgene DNA into the mitochondrial matrix in living mammalian cells. The unavailability of a mitochondria-specific reporter plasmid designed for mitochondrial expression severely hampers current efforts toward the development of effective mitochondrial expression vectors. Although any new nonviral transfection system (i.e., cationic lipids, polymers, and others) aimed at the nuclear-cytosolic expression of proteins can be systematically tested and subsequently improved by utilizing anyone of many commercially available reporter gene systems, such a methodical approach to develop mitochondrial transfection systems is currently impossible. 

These are an example of a nonviral vector that can accept large DNA inserts. Because the liposome lacks peptides, it does not provoke an immune response. The primary disadvantage is that, unlike viruses, the integration rate of liposome-contained DNA is very low. 

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