Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides.
We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by tat protein, the functional protein of the transactivator gene. We selected the target sequence localized near the 5' end of the tat mRNA. The following conclusions can be drawn from the data presented here: a) Antisense oligonucleotides modified by conjugation of cholesterol at the 3' end have a severalfold higher inhibitory response, b) inhibitory response is dependent on the mode of introducing oligonucleotides, and c) the inhibition by antisense oligonucleotides is sequence specific and directed towards the targeted region. This approach could be useful for targeting functional regions of regulatory gene products and designing gene-targeted inhibitors of virus replication.
Demirhan
I
I
Laboratory of Molecular Biology, Frankfurt University School of Medicine, FRG.
Hasselmayer
O
O
Hofmann
D
D
Chandra
A
A
Svinarchuk
F P
FP
Vlassov
V V
VV
Engels
J
J
Chandra
P
P
D000818:Animals; D001483:Base Sequence; D002415:Cats / Q000235:genetics; D002460:Cell Line; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D018390:Gene Targeting; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016376:Oligonucleotides, Antisense; D054322:tat Gene Products, Human Immunodeficiency Virus