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Titolo:
SEQUENCE-SPECIFIC INHIBITION OF GENE-EXPRESSION BY A NOVEL ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE DIRECTED AGAINST A NONREGULATORYREGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GENOME
Autore:
ANAZODO MI; WAINBERG MA; FRIESEN AD; WRIGHT JA;
Indirizzi:
UNIV MANITOBA,MANITOBA INST CELL BIOL,100 OLIVIA ST WINNIPEG MB R3E 0V9 CANADA UNIV MANITOBA,MANITOBA INST CELL BIOL WINNIPEG MB R3E 0V9 CANADA UNIV MANITOBA,DEPT BIOCHEM & MOLEC BIOL WINNIPEG MB R3E 0V9 CANADA SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES MONTREAL PQ H3T 1E2 CANADA MCGILL UNIV,DEPT MED MONTREAL PQ H3T 1E2 CANADA MCGILL UNIV,MCGILL AIDS CTR MONTREAL PQ H3T 1E2 CANADA GENESYS PHARMA INC WINNIPEG MB R3P 1P4 CANADA
Titolo Testata:
Journal of virology
fascicolo: 3, volume: 69, anno: 1995,
pagine: 1794 - 1801
SICI:
0022-538X(1995)69:3<1794:SIOGBA>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIBODY-TARGETED LIPOSOMES; CHRONICALLY INFECTED-CELLS; LATE REPLACEMENT VECTOR; RIBONUCLEOTIDE REDUCTASE; NUCLEOTIDE-SEQUENCE; VIRAL-RNA; HTLV-III; OLIGONUCLEOTIDES; REPLICATION; DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
M.I. Anazodo et al., "SEQUENCE-SPECIFIC INHIBITION OF GENE-EXPRESSION BY A NOVEL ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE DIRECTED AGAINST A NONREGULATORYREGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GENOME", Journal of virology, 69(3), 1995, pp. 1794-1801

Abstract

Previous studies have demonstrated that oligodeoxynucleotide phosphorothioates complementary to human immunodeficiency virus type 1 (HIV-1)RNA are more nuclease resistant and are effective inhibitors of HIV-1replication than their unmodified counterpart. In this study, antisense oligodeoxynucleotide sequences were evaluated for therapeutic potential in the treatment of HIV infections. The use of HN-infected lymphocytes to test the efficacy of a drug is very complex, and therefore itis difficult to draw conclusions about the mechanism. We used a COS-like Monkey kidney cell line (CMT3) stably transfected with plasmids pCMVgagpol-rre-r (containing gag and pal genes) and pCMVrev (containing the rev gene of HIV-1), derived from cDNA clone BH10, as a model. A biologically active provirus that transcribes and translates their nucleotide sequences into viral proteins p24, p39/41, p55, and p160 was generated. Sequence-specific and dose-dependent inhibition of HIV-1 viralprotein synthesis and significant inhibition at the mRNA level were demonstrated by antisense construct GPI2A, directed against a nonregulatory region of the HIV-1 genome. Also, our studies demonstrated enhancement of the antisense effect through encapsulation in a cationic lipid preparation. The observed attenuation of HIV-1 mRNA levels suggests that, at least in part, the mechanism of action of GPI2A was at the transcript level. Further studies have also shown antiviral activity of this construct as determined by the reverse transcriptase assay using acutely and chronically infected cells of lymphoid origin (H9 cells). Toxicological studies involving cell growth characteristics, colony-forming ability, effects on cellular proteins, specific activities of labeled proteins, and DNA synthesis in cell culture showed no cytotoxic effects of GPI2A.

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Documento generato il 24/10/20 alle ore 11:40:56