Antiviral activity of steric-block oligonucleotides targeting the HIV-1 trans-activation response and packaging signal stem-loop RNAs.
Mixmer oligonucleotides consisting of residues of both 2'-O-methylnucleosides (OMe) and locked nucleic acids (LNA) were designed targeting two stem-loops in the 5'-UTR of HIV-1 RNA, the transactivation response region (TAR), which is the site of binding of the Tat protein, and the SL3 loop, which is the primary packaging element that binds the Gag polyprotein. These oligonucleotides were found to inhibit syncitia formation dose- and sequence-dependently when delivered to HeLa T4 LTR beta-Gal cells and subsequently infected with HIV-1.
Brown
Douglas
D
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ. UK.
Arzumanov
Andrey A
AA
Turner
John J
JJ
Stetsenko
Dmitry A
DA
Lever
Andrew M L
AM
Gait
Michael J
MJ
D020121:5' Untranslated Regions; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D004305:Dose-Response Relationship, Drug; D015683:Gene Products, gag / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry*; D020218:Response Elements; D015533:Transcriptional Activation; D001616:beta-Galactosidase / Q000378:metabolism
D020121:5' Untranslated Regions; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015683:Gene Products, gag; D009841:Oligonucleotides; D012313:RNA; D001616:beta-Galactosidase