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 S I nuclease. In particular, PNIPAAm-modified antisense ODN at the 3,5'-ends of the ODN provided complete resistance against nuclease at 37 degreesC, 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. (C) 2003 Elsevier Ltd. All rights reserved.