Specific inhibition of influenza virus RNA polymerase and nucleoprotein gene expression by circular dumbbell RNA/DNA chimeric oligonucleotides containing antisense phosphodiester oligonucleotides

FEBS Letters
T AbeH Takaku

Abstract

We have designed a new class of oligonucleotides, 'dumbbell RNA/DNA chimeric oligonucleotides', consisting of a sense RNA sequence and its complementary antisense DNA sequence, with two hairpin loop structures. The reaction of the nicked (NDRDON) and circular (CDRDON) dumbbell RNA/ DNA chimeric oligonucleotides with RNase H gave the corresponding antisense phosphodiester oligodeoxynucleotide together with the sense RNA cleavage products. The liberated antisense phosphodiester oligodeoxynucleotide was bound to the target RNA, which gave RNA cleavage products by treatment with RNase H. The circular dumbbell RNA/DNA chimeric oligonucleotide showed more nuclease resistance than the linear antisense phosphodiester oligonucleotide (anti-ODN) and the nicked dumbbell RNA/DNA chimeric oligonucleotide. The CDRDON with four target sites (influenza virus A RNA polymerases (PB1, PB2, PA) and nucleoprotein (NP)) was synthesized and tested for inhibitory effects by a CAT-ELISA assay using the clone 76 cell line. The circular dumbbell DNA/ RNA chimeric oligonucleotide (CDRDON-PB2-as) containing an AUG initiation codon sequence as the target of PB2 showed highly inhibitory effects.

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Citations

Apr 6, 2004·Current Opinion in Pharmacology·Ryuichi MorishitaToshio Ogihara
Feb 5, 2000·Bioorganic & Medicinal Chemistry·Z JiangS Agrawal
Sep 30, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Takashi MiyakeRyuichi Morishita
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Jan 22, 2010·Molekuliarnaia biologiia·M Iu Skoblov
Apr 9, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·T AbeH Takaku
Aug 3, 2013·Marine Biotechnology·Sajad AhangerRakesh K Mishra
Mar 27, 2007·Clinical and Experimental Nephrology·Naruya TomitaRyuichi Morishita
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Aug 21, 2003·Biochemical and Biophysical Research Communications·Kwan-Kyu ParkYoung-Chae Chang
Jun 27, 2007·Bioorganic & Medicinal Chemistry Letters·Xinming LiTianhu Li
May 21, 2008·Bioorganic & Medicinal Chemistry Letters·Yifan WangTianhu Li

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