SPECIFIC-INHIBITION OF INFLUENZA-VIRUS RNA-POLYMERASE AND NUCLEOPROTEIN GENE-EXPRESSION BY CIRCULAR DUMBBELL RNA DNA CHIMERIC OLIGONUCLEOTIDES CONTAINING ANTISENSE PHOSPHODIESTER OLIGONUCLEOTIDES/

We hale designed a new class of oligonucleotides, 'dumbbell RNA/DNA ch imeric oligonucleotides', consisting of a sense RNA sequence and its c omplementary antisense DNA sequence, with tno hairpin loop structures. The reaction of the nicked (NDRDON) and circular (CDRDON) dumbbell RN A/DNA chimeric oligonucleotides with RNase H gave the corresponding an tisense phosphodiester oligodeoxynucleotide together with the sense RN A cleavage products. The liberated antisense phosphodiester oligodeoxy nucleotide was bound to the target RNA, which gave RNA cleavage produ cts by treatment with RNase H, The circular dumbbell RNA/DNA chimeric oligonucleotide showed more nuclease resistance than the linear antise nse phosphodiester oligonucleotide (anti-ODN) and the nicked dumbbell RNA/DNA chimeric oligonucleotide, The CDRDON with four target sites (i nfluenza virus A RNA polymerases (PB1, PB2, PA) and nucleoprotein (NTP )) was synthesized and tested for inhibitory effects by a CAT-ELISA as say using the clone 76 cell line, The circular dumbbell DNA/RNA chimer ic oligonucleotide (CDRDON-PB2-as) containing an AUG initiation codon sequence as the target of PB2 shelved highly inhibitory effects. (C) 1 998 Federation of European Biochemical Societies.