Gene therapy via inducible nitric oxide synthase: a tool for the treatment of a diverse range of pathological conditions.
Nitric oxide (NO(.)) is a reactive nitrogen radical produced by the NO synthase (NOS) enzymes; it affects a plethora of downstream physiological and pathological processes. The past two decades have seen an explosion in the understanding of the role of NO(.) biology, highlighting various protective and damaging modes of action. Much of the controversy surrounding the role of NO(.) relates to the differing concentrations generated by the three isoforms of NOS. Both calcium-dependent isoforms of the enzyme (endothelial and neuronal NOS) generate low-nanomolar/picomolar concentrations of NO(.). By contrast, the calcium-independent isoform (inducible NOS (iNOS)) generates high concentrations of NO(.), 2-3 orders of magnitude greater. This review summarizes the current literature in relation to iNOS gene therapy for the therapeutic benefit of various pathological conditions, including various states of vascular disease, wound healing, erectile dysfunction, renal dysfunction and oncology. The available data provide convincing evidence that manipulation of endogenous NO(.) using iNOS gene therapy can provide the basis for future clinical trials.
McCarthy
Helen O
HO
School of Pharmacy, McClay Research Centre, Queen's University, Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK. h.mccarthy@qub.ac.uk
Coulter
Jonathan A
JA
Robson
Tracy
T
Hirst
David G
DG
D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D007172:Erectile Dysfunction / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007674:Kidney Diseases / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D014945:Wound Healing / Q000235:genetics
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II