Gene delivery system nonviral vectors

Despite improvement in nonviral gene delivery systems, viral vectors continue to have higher efficiency in most experimental systems. Adenovirus, adeno-associated virus, retrovirus, lentivirus, herpes simplex viras, and others have been used both in the laboratory, and to a much lesser extent, in human trials. Of these potential vectors, studies of adenoviras in the pulmonary circulation are the only ones in the published literature. 

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... 

Nonviral vector systems are usually either composed of a plasmid based expression cassette alone ( naked DNA), or are prepared with a synthetic amphipathic DNA-complexing agent (84, 88). Gene delivery systems based on nonviral vectors mainly comprise cationic liposomes, DNA-polymer-protein complexes, and mechanic administration of naked DNA. An idealized/optimized multifunctional nonviral gene delivery system is depicted in Figure 13.4. 

Safinya CR, Koltover I (1999) Self assembled structures of lipid-DNA nonviral gene delivery systems from synchrotron X-ray diffraction. In Huang L, Hung M-C, Wagner E (eds) Nonviral vectors for gene therapy. Academic, San Diego... 

The prerequisites of successful HGT include therapeutically suitable genes (with a proven role in pathophysiology of the disease either by its lack, mutation, or overexpression), appropriate gene delivery systems (e.g., viral and nonviral vectors), proof of principle of efficacy and safety in appropriate preclinical models, and suitable manufacturing and analytical processes to provide well-defined HGT products for clinical investigations. 

Currently, transport of exogenous DNA to cells can be achieved using viral and nonviral vectors or as naked DNA. The simplest nonviral gene delivery system simply uses naked DNA. The overall level of expression is much lower with naked DNA than with either viral or liposomal vectors. Naked DNA is also unsuitable for systemic administration due to the presence of serum nucleases. 

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. 

Most of today s approved biotechnology products are produced in bacteria, yeast, or mammalian cells. Newer sources currently used to manufacture clinical trial materials include insect cells, transgenic animals, and gene therapy vectors. Other potential sources include transgenic plants and nonviral delivery systems... 

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