Targeting of the renin-angiotensin system by antisense gene therapy: a possible strategy for the long-term control of hypertension.
Traditional pharmacological agents have been successfully used for the treatment of hypertension for a number of decades. However, this therapeutic regimen has reached a conceptual plateau and a cure for the disease is far from appearing on the horizon. With this in mind, and recent advances in state of the art gene delivery system coupled with the anticipated completion of the human genome project, it is timely to think about the possibility of treating and/or curing hypertension using genetic means. In this review, we discuss the role of renin-angiotensin system (RAS) in hypertension; the current gene delivery/gene transfer systems and the RAS as a target for gene therapy to treat hypertension; the successful use of retroviral vectors to deliver antisense to the AT1 receptor (AT1-AS) to prevent the development of hypertension and cardiovascular pathophysiology; the potential use of the viral vectors for the reversal of hypertension; and the future of antisense gene therapy and potential advantages and limitations of this regimen in the treatment and/or control of hypertension.
Raizada
M K
MK
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610-0274, USA. mraizada@phys.med.ufl.edu
Francis
S C
SC
Wang
H
H
Gelband
C H
CH
Reaves
P Y
PY
Katovich
M J
MJ
D000818:Animals; D018390:Gene Targeting; D006801:Humans; D006973:Hypertension / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000235:genetics*; D013997:Time Factors
D016376:Oligonucleotides, Antisense