Inhibition of HIV-1 replication by oligonucleotide analogues directed to the packaging signal and trans-activating response region.
HIV possesses a remarkable capacity for mutational escape from therapeutics that target the viral proteins and enzymes. Inhibitory strategies aimed at highly conserved nucleic acid sequences within the genome are an attractive alternative. However, it has proven difficult to achieve an effective level of therapeutic at the appropriate site within the cell. Oligonucleotide delivery is a rapidly advancing field. We have investigated oligonucleotide analogues as steric-block therapeutics against two highly conserved regions of the HIV-1 genome. In the study we show that 2'0-methyl/locked nucleic acid oligonucleotides against the packaging signal and trans-activating response regions of HIV can inhibit replication of the virus.
University of Cambridge, Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.
Douglas E
DE
Brown
Andrey
A
Arzumanov
Sana
S
Syed
Michael J
MJ
Gait
Andrew M L
AM
Lever
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005456:Fluorescent Dyes / Q000737:chemistry; D015658:HIV Infections / Q000235:genetics / Q000628:therapy* / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence; D009841:Oligonucleotides / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication / Q000235:genetics*
D005456:Fluorescent Dyes; D009841:Oligonucleotides; D012194:RNA-Directed DNA Polymerase