Gene therapy of focal cerebral ischemia using defective recombinant adeno-associated virus vectors.
This review presents our experience and results concerning cerebral stroke gene therapy with a rat model subjected to rAAV-vector delivered IL-1ra and GDNF. The methodology involving the production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus and the creation of a tri-vessel ligation model of focal ischemic cerebral stroke in rats are described in detail. Furthermore, a literature review of other viral vectors, murine models of focal cerebral ischemia and candidates for therapeutic transgenes used for cerebral stroke gene therapy are presented. Lastly, the potentials and limitations of stroke gene therapy are discussed adding an analysis of possibilities of future experiment designs.
Tsai
Tung-Han
TH
Department of Neurosurgery, Tri-Service General Hospital, Taipei, Taiwan.
Chen
Show-Li
SL
Xiao
Xiao
X
Chiang
Yung-Hsiao
YH
Tsao
Yeou-Ping
YP
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000502:physiology; D001929:Brain Edema / Q000235:genetics / Q000628:therapy; D002545:Brain Ischemia / Q000235:genetics* / Q000628:therapy*; D002118:Calcium / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D014162:Transfection; D019076:Transgenes
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D017382:Reactive Oxygen Species; D017472:Receptors, Interleukin-1; D002118:Calcium