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 degrees 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.
Murata
Masaharu
M
Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Fukuoka 812-8581, Japan. muratatcm@mbox.nc.kyushu-u.ac.jp
Kaku
Wataru
W
Anada
Takahisa
T
Sato
Yoshikuni
Y
Kano
Takeshi
T
Maeda
Mizuo
M
Katayama
Yoshiki
Y
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D007202:Indicators and Reagents; D007700:Kinetics; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000138:chemical synthesis* / Q000494:pharmacology*
D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D004247:DNA; D003851:Deoxyribonucleases