INHIBITORY PROPERTIES OF DOUBLE HELIX-FORMING CIRCULAR OLIGONUCLEOTIDES

Several circular oligonucleotides were synthesized and characterized b y electrospray ionization mass spectrometry. Experiments on terminatio n of primer extension catalysed by DNA polymerases, Klenow fragment an d Tth have demonstrated that a double helix forming circular 2'-deoxyr ibooligomer containing a 25mer sequence complementary to the target si ngle-stranded DNA along with a 34mer random mismatching stretch appear s to be a potent inhibitor of replication in vitro. Studies on inhibit ion of luciferase gene expression in a cell-free transcription-transla tion system have shown that a duplex forming circular 2'-deoxyriboolig onucleotide containing a 25mer sequence complementary to the target mR NA and a 14mer random mismatching stretch can serve as an effective an tisense compound as a standard linear complementary oligomer, Features of double helix forming circular oligonucleotides composed of 2'-deox yribonucleosides seem to be useful for the design of new antigene and antisense agents.