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Titolo:
Gene therapy for hypertension: sense and antisense strategies
Autore:
Phillips, MI;
Indirizzi:
Univ Florida, Coll Med, Dept Physiol, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 Physiol, Gainesville, FL 32610 USA
Titolo Testata:
EXPERT OPINION ON BIOLOGICAL THERAPY
fascicolo: 4, volume: 1, anno: 2001,
pagine: 655 - 662
SICI:
1471-2598(200107)1:4<655:GTFHSA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH BLOOD-PRESSURE; RECEPTOR MESSENGER-RNA; DELIVERY ATTENUATES HYPERTENSION; PROLONGED REDUCTION; AT(1) RECEPTOR; RENAL INJURY; INHIBITION; RATS; OLIGODEOXYNUCLEOTIDES; ANGIOTENSINOGEN;
Keywords:
adeno-associated virus; angiotensin; antisense oligodeoxynucleotides; hypertension;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Phillips, MI Univ Florida, Coll Med, Dept Physiol, Box 100274, Gainesville, FL 32610 USA Univ Florida Box 100274 Gainesville FL USA 32610 FL 32610 USA
Citazione:
M.I. Phillips, "Gene therapy for hypertension: sense and antisense strategies", EXPERT OP B, 1(4), 2001, pp. 655-662

Abstract

Gene therapy for hypertension is needed for the next generation of antihypertensive drugs. Current drugs, although effective, have poor compliance, are expensive and short-lasting (hours or one day). Gene therapy offers a way to produce long-lasting anti hypertensive effects (weeks, months or years). We are currently using two strategies: antisense oligodeoxynucleotides (AS-ODN), andantisense DNA delivered in viral vectors, to inhibit genes associated with vasoconstrictive properties. It is not necessary to know all the genes involved in hypertension, since many years of experience with drugsshow which genes need to be controlled. AS-ODNs are short, single-strandedDNA that can be injected in naked form or in liposomes. AS-ODNs, targeted to AT(1) receptors (AT(1)R), angiotensinogen (AGT), angiotensin converting enzyme (ACE) and beta (1)-adrenergic receptors effectively reduce hypertension in rat models (SHR, 2K-1C and cold-induced) hypertension. The effects can last up to one month when delivered with liposomes. No side effects or toxic effects have been detected and repeated injections can be given. For the vector, adeno-associated virus (AAV) is used with a construct to includea CMV promoter, antisense DNA to AGT or AT1R and a reporter gene. Results in SHR demonstrate reduction and slowing of hypertension development with asingle dose administration. Left ventricular hypertrophy is also reduced by AAVAS-AGT treatment. Double transgenic mice (human renin plus human AGT) with high angiotensin II (Ang II) causing high blood pressure, treated withAAV-AT,R-AS, show a normalisation of blood pressure for over 6 months witha single injection of vector. We conclude that ODNs will probably be developed first because they can be treated like drugs for the treatment of hypertension with long-term effects. Viral vector delivery needs more engineering to be certain of its safety but one day may be used for a very prolongedcontrol of blood pressure.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 17:05:08