A NOVEL-APPROACH FOR GENE MEDICINE - SYNTHETIC POLY-L-LYSINE SERINE COPOLYMER ENHANCES BIOACTIVITY OF ANTISENSE OLIGONUCLEOTIDES/

Antisense oligonucleotides have therapeutic potential as inhibitor of gene expression. Water soluble and nuclease resistant-polymers complex ed with the antisense oligodeoxynucleotide which specifically inhibits the production of interleukin-1 beta were prepared using poly-L-lysin e/L-serine and its polyethylene glycol 5000 conjugate and evaluated th eir activity in vitro and in vivo. These complexes biologically inhibi ted interleukin-1 beta production in a dose-dependent and sequence-spe cific manner at nanomolar levels in lipopolysaccride-stimulated human macrophage-like, U937 cells. Moreover, in vivo studies using mouse end otoxin shock model, it had a strong efficacy in a dose-dependent and s equence-specific manner. The mice (n=10), administered with the antise nse complex at 100 mg/kg, survived for more than 7 days. These carrier s may give a promise for developing nucleic acid drug in clinical use.