Elevated messenger RNA levels after antisense oligodeoxynucleotide treatment in vitro and in vivo.
Antisense oligodeoxynucleotides are being increasingly employed in various fields of biological research. Not only has the antisense mediated inhibition of gene expression become a valuable experimental tool, the synthetic oligodeoxynucleotides are also considered to be potential therapeutic drugs. Despite the huge body of literature regarding antisense treatment, there is little information on the mode of action. Currently, the main view is that antisense oligodeoxynucleotides bind to the target mRNA and thus trigger RNase H-directed cleavage of the newly formed RNA-DNA duplex molecules. Here we present data from in vitro and in vivo experiments showing that antisense oligodeoxynucleotide treatment does not necessarily lead to a reduction of the corresponding mRNA levels. In fact, mRNA levels can be clearly elevated. These results favor the view that antisense oligodeoxynucleotides, presumably in a large number of neurobiological applications, function via hybrid arrested translation rather than RNase H-driven mRNA cleavage.
Probst
J C
JC
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
Skutella
T
T
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006133:Growth Substances / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D016914:Ribonuclease H / Q000378:metabolism; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D017931:DNA Primers; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense; D010455:Peptides; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014446:Tyrosine 3-Monooxygenase; D016914:Ribonuclease H