Antisense oligonucleotides strategy in the treatment of hypertension.
Many kinds of drugs are used for the treatment of hypertension, but they are all short-acting (< or = 24 h) and patient compliance is poor. Gene therapy offers the advantage of producing long-term effects with high specificity, which should increase efficacy and reduce side effects. An antisense oligodeoxynucleotide (AS ODN) is a single-stranded oligonucleotide containing a gene-specific sequence of nucleotides, which is used to inhibit translation of mRNA. The application of AS ODNs for the treatment of hypertension began with targeting the renin-angiotensin system. Other genes, such as that coding for the beta1-adrenoceptor, have recently been targeted with AS ODNs in an attempt to reduce blood pressure. Strategies for the application of antisense technologies can be classified in two ways: the direct application of AS ODNs, and the production of AS by AS-cDNA inserted into viral vectors. Promising preclinical results from basic research have made feasible the possibility for antisense gene therapy of hypertension in the future.
Kagiyama
S
S
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610-0274, USA.
Kagiyama
T
T
Phillips
M I
MI
D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016234:Kallikrein-Kinin System / Q000235:genetics / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D013873:Thionucleotides / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D018406:Virus Physiological Phenomena
D016376:Oligonucleotides, Antisense; D018342:Receptors, Adrenergic, beta-1; D013873:Thionucleotides