Novel DNA/Polymer conjugate for intelligent antisense reagent with improved nuclease resistance

Antisense technology provides an effective strategy to inhibit synthesis of the gene product. We prepared a novel antisense reagent comprised of oligodeoxynucleotides (ODN) and a thermo responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm). The conjugate inhibited gene expression in a dose-dependent manner. The ODN–PNIPAAm conjugate demonstrated excellent resistance to S1 nuclease. In particular, PNIPAAm-modified antisense ODN at the 3′,5′-ends of the ODN provided complete resistance against nuclease at 37 °C, which is above the phase transition temperature of the PNIPAAm side chain. These characteristics of the conjugate suggest it may have potential for use in a new gene delivery system as part of an antisense strategy.