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• W2137147170 endingPage "325" @default.
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• W2137147170 abstract "Human immunodeficiency virus type 1 (HIV-1) encodes two regulatory proteins, Tat and Rev, that bind to target RNA sequences. These are the trans-activation responsive (TAR) RNA and the Rev-responsive element (RRE), respectively. The Rev protein shifts RNA synthesis to viral transcripts by binding to the RRE within the env gene. In the present study we prepared a RNA-DNA chimera consisting of 29 or 31 nucleotides to inhibit the Rev regulatory function by means of the decoy approach. The chimera oligonucleotides (anti-Rev oligonucleotides [AROs]) contained an RNA bubble structure (13 oligonucleotides; the Rev-binding element in RRE) that bound Rev with a high affinity in an in vitro assay. The controls were RNA-DNA chimera oligonucleotides (negative control oligonucleotides [NCOs]) similar to ARO, but without the bubble structure, that bound with considerably less affinity to Rev. When the inhibitory effects of these decoys on HIV-1 replication were examined, we found that AROs, but no NCOs, reduced more than 90% of the HIV-1 production generated by productively infected human T-cell lines. The production of primary HIV-1 isolates in healthy donor-derived peripheral blood mononuclear cells was also similarly inhibited by AROs. In addition, the induction of viral mRNAs and antigens in latently HIV-1-infected ACH-2 cells by tumor necrosis factor alpha was specifically inhibited by AROs, but not by NCOs. No apparent cytotoxicity was caused by either decoy. Thus, the use of a Rev-binding element-based decoy, the RNA-DNA chimera oligonucleotide, may represent a safer approach to gene therapy for reducing the virus load in HIV-1-infected individuals." @default.
• W2137147170 created "2016-06-24" @default.
• W2137147170 creator A5016195460 @default.
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• W2137147170 creator A5075490359 @default.
• W2137147170 date "1997-02-01" @default.
• W2137147170 modified "2023-10-16" @default.
• W2137147170 title "Decoy approach using RNA-DNA chimera oligonucleotides to inhibit the regulatory function of human immunodeficiency virus type 1 Rev protein" @default.
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• W2137147170 doi "https://doi.org/10.1128/aac.41.2.319" @default.
• W2137147170 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/163708" @default.
• W2137147170 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9021186" @default.
• W2137147170 hasPublicationYear "1997" @default.
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