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Titolo:
Novel mono- and di-DNA-enzymes targeted to cleave TAT or TAT-REV RNA inhibit HIV-1 gene expression
Autore:
Unwalla, H; Banerjea, AC;
Indirizzi:
Natl Inst Immunol, Virol Lab, New Delhi 110067, India Natl Inst Immunol New Delhi India 110067 ol Lab, New Delhi 110067, India
Titolo Testata:
ANTIVIRAL RESEARCH
fascicolo: 2, volume: 51, anno: 2001,
pagine: 127 - 139
SICI:
0166-3542(200108)51:2<127:NMADTT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
VIRUS TYPE-1 EXPRESSION; MESSENGER-RNA; IN-VITRO; RIBOZYME; CELLS; REPLICATION; INFECTIVITY; PROTEIN; ENV;
Keywords:
RNA cleaving DNA-enzyme; HIV-1 TAT; REV and ENV;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Banerjea, AC Natl Inst Immunol, Virol Lab, Aruna Asaf Ali Marg,JNU Campus,New Delhi 110067, India Natl Inst Immunol Aruna Asaf Ali Marg,JNU Campus New Delhi India 110067
Citazione:
H. Unwalla e A.C. Banerjea, "Novel mono- and di-DNA-enzymes targeted to cleave TAT or TAT-REV RNA inhibit HIV-1 gene expression", ANTIVIR RES, 51(2), 2001, pp. 127-139

Abstract

The regulatory proteins TAT and REV play a very important role in the transcription and replication of HIV-1. In order to seHIV-01lectively down regulate the expression of these genes we synthesized several mono- and one di-DNA-enzyme against the TAT or TAT-REV RNA. Several mono-DNA-enzymes possessing the 10-23 catalytic motif were assembled that were targeted to the predicted loop region of TAT or TAT/REV RNA. The cleavage efficiency of each mono-DNA-enzyme was variable and independent of the size of the predicted loop structure of the target RNA. DNA-enzyme targeted against the largest loopregion cleaved the substrate RNA poorly. Mono-DNA-enzyme-5944 that targetsonly the TAT region cleaved the substrate poorly but the DNA-enzyme-5970 that overlaps TAT and REV showed potent cleavage activity. The two DNA-enzymes, when placed in tandem, cleaved the target RNA at multiple sites that were specific for the two mono-DNA-enzymes. Only Dz-5970 retained the abilityto cleave the target RNA specifically at simulated physiological conditions. They were able to inhibit HIV-1 specific genes efficiently when introduced into a mammalian cell. The extent of inhibition correlated with their cleavage efficiency obtained at standard conditions of cleavage. Although DNA-enzyme-5970 showed the highest reduction (similar to 90%), other DNA-enzymes (mono-DNA-enzyme-5944 and the di-DNA-enzyme) also showed reduction to anextent of 60 and 80% respectively. The inhibitory effect of the DNA-enzymecould be overcome by providing HIV-1 TAT to the cells. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 22:57:32