title: Mechanisms of the inhibition of reverse transcription by unmodified and modified antisense oligonucleotides.
abstract: We have demonstrated that the synthetic oligonucleotides, either unmodified or phosphorothioates, prevent cDNA synthesis by the AMV or HIV reverse transcriptases. The RNA was truncated at the antisense oligonucleotide-RNA duplex during the reverse transcription. Th blockage involves the degradation of the RNA fragment bound to the antisense oligonucleotide by the reverse transcriptase associated RNase H activity. However, in the case of phosphorothioate oligomer, the production of cDNA would be inhibited by a hybrid formed between the AMV RT and phosphorothioate oligomer than arrested elongation of the cDNA strands, whereas arrest of a growing cDNA strand by HIV RT can be blocked by an oligonucleotide complementary to a region downstream from the primer.
authors.affiliation: Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hatta
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D018076:DNA, Complementary / Q000096:biosynthesis; D005914:Globins / Q000235:genetics; D006678:HIV / Q000201:enzymology; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides; D005914:Globins