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Novel stabilizing method for unmodified oligodeoxynucleotides (ODNs) has been investigated. Chemically modified ODNs, which carry complementary sequences of unmodified antisense ODN, can form a double-stranded complex with the ability to stabilize the unmodified oligomer. The modifications were made on phosphodiester back-bone (phosphorothioate, SO), thymine base (5-phenylethyl substitution), 5'-terminal(introduction of poly(ethylene glycol)). To determine the potential of this method, the in vitro stability in human plasma and in vivo retention in mouse after iv injection of the hemi-modified double-stranded ODNs were evaluated. Dissociation of unmodified antisensc ODN from the hemi modified double-strand and reconstitution of the double-strand with an unmodified sense ODN were also recognized

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Enzymatic stability and plasma concentration of double-stranded oligodeoxynucleotides(ODNs) composed of unmodified antisense ODN and chemicaly modified sense ODNs.