Nonviral gene therapy

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). 

Tomlinson, E., and Rolland, A.P., Controllable gene therapy pharmaceutics of nonviral gene delivery systems, Journal of Controlled Release, 1995, 39, 357-372. 

Fewell JG, Matar MM, Rice JS, Brunhoeber E, Slobodkin G, Pence C, Worker M, Lewis DH, Anwer K (2009) Treatment of disseminated ovarian cancer using nonviral interleukin-12 gene therapy delivered intraperitoneally. J Gene Med 11 718-728... 

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. 

Feigner PL. Nonviral strategies for gene therapy. Scientific American June 103-106 (1997). 

Tecle M, Preuss M, Miller AD. Kinetic study of DNA condensation by cationic peptides used in nonviral gene therapy analogy of DNA condensation to protein folding. Biochemistry 2003 42 10343-10347. 

The investigators evaluated the safety of their nonviral somatic-cell gene therapy system, which they call transkaryotic implantation, in six patients with severe hemophilia. The procedure involved isolation of dermal fibroblasts from the patients upper arms. The fibroblasts were then transfected with a factor VIII genebearing plasmid. Cells that expressed factor VIII were cloned, propagated, and implanted into the patients abdomens. This technique can be considered as a less invasive form of ex vivo gene therapy. 

Gene Therapy An Overview of the Current Viral and Nonviral Vectors...333... 

The simplest nonviral gene transfer system in use for gene therapy is the injection of naked plasmid DNA (pDNA) into local tissues or the systemic circulation (88, 100). Naked DNA systems are composed of a bacterial plasmid that contains the cDNA of a reporter or therapeutic gene under the transcriptional control of various regulatory elements (101, 102). In recent years, work in several laboratories has shown that naked plasmid DNA (pDNA) can be delivered efficiently to cells in vivo either via electroporation, or by intravascular delivery, and has great prospects for basic research and gene therapy (101). Efficient transfection levels have also been obtained on direct application of naked DNA to the liver (103, 104), solid tumours (105), the epidermis (106), and hair follicles (106). 

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