In vitro and in vivo pharmacologic activities of antisense oligonucleotides.
The use of antisense oligonucleotide as pharmacologic agents is a derivative of the central dogma of molecular biology and knowledge of the physical and chemical properties that govern the structure of nucleic acids. Oligonucleotides have been reported to inhibit the growth of a large number of viruses in cell culture, as well as the expression of numerous oncogenes, a variety of normal genes and transfected reporter genes controlled by several regulatory elements. The therapeutic activity of antisense compounds in animal disease models have also been reported. This review provides some general conclusions and trends regarding the pharmacologic action of antisense oligonucleotides, that can be formulated from studies previously reported in the literature. In addition, data is highlighted for two specific examples in which antisense oligonucleotides have demonstrated activity against herpes viruses and intracellular adhesion molecule RNA targets.
Mirabelli
C K
CK
ISIS Pharmaceuticals, Inc., Carlsbad, CA 92008.
Bennett
C F
CF
Anderson
K
K
Crooke
S T
ST
D000818:Animals; D015815:Cell Adhesion Molecules / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects
D015815:Cell Adhesion Molecules; D016376:Oligonucleotides, Antisense