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Titolo:
Gene therapy for hypertension - The preclinical data
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:
HYPERTENSION
fascicolo: 3, volume: 38, anno: 2001,
parte:, 2 supplemento:, S
pagine: 543 - 548
SICI:
0194-911X(200109)38:3<543:GTFH-T>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH BLOOD-PRESSURE; DELIVERY ATTENUATES HYPERTENSION; RECEPTOR MESSENGER-RNA; VIRAL VECTOR DELIVERY; SALT-SENSITIVE RATS; IN-VIVO TRANSFER; ANTISENSE OLIGODEOXYNUCLEOTIDES; PROLONGED REDUCTION; RENAL INJURY; ANGIOTENSINOGEN GENE;
Keywords:
genes; drug therapy; kallkirein; renin angiotensin system; adrenergic receptor blockers; oligonucleotides; antisense; adeno-associated virus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
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 - The preclinical data", HYPERTENSIO, 38(3), 2001, pp. 543-548

Abstract

Despite several drugs for the treatment of hypertension, there are many patients with poorly controlled high blood pressure. This is partly because all of the available drugs are short-lasting (less than or equal to 24 hours), have side effects, and are not highly specific. Gene therapy offers a possibility of producing longer-lasting effects with precise specificity based on the genetic design. Preclinical studies on gene therapy for hypertension have taken 2 approaches. Chao et al have performed extensive studies on gene transfer to increase vasodilator proteins. They have transferred kallikrein, atrial natriuretic peptide, adrenomedullin, and endothelin NO synthase into different rat models. Their results show that blood pressure can belowered for 3 to 12 weeks with the expression of these genes. The antisense approach, which we began by targeting angiotensinogen and the angiotensintype 1 (AT(1)) receptor, has now been tested independently by several different groups in multiple models of hypertension. Other genes targeted include the beta (1)-adrenoceptor, thyrotropin-releasing hormone, angiotensin gene-activating elements, carboxypeptidase Y, c-fos, and CYP4A1 There have been 2 methods of delivering antisense: one is by oligodeoxynucleotides, and the other is with full-length DNA in viral vectors. All the studies show a decrease in blood pressure lasting several days to weeks or months. Oligos are safe and nontoxic and could be delivered orally or eventually by skin patches. Systemic delivery of recombinant adeno-associated virus with DNA antisense to AT, receptors in adult rodents decreases hypertension for up to 6 months. We conclude that there is sufficient preclinical data to give serious consideration to phase I trials for testing some of the antisense oligodeoxynucleotides, although testing the viral vectors needs much more work.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 02:18:02