Antiproliferative effects of antisense oligonucleotides directed to the RNA ofc-myconcogene

Abstract

Several groups have reported the use of antisense oligonucleotides to inhibit c-myc gene expression and study its biological role. However high concentrations of free oligonucieotides were generally needed. To lower their concentration and stabilize the antisense effect against c-myc, oligonucleotides were covalently linked to poly(L-lysine) and administered in ternary complexes formed with heparin (100 μg/ml). A sequence specific growth inhibition was observed at concentrations lower than 1μM, while oligonucieotide poly(L-lysine) conjugates alone were inefficient. Similar results occured with other polyanionic compounds. Inhibition of proliferation was correlated to a reduction of c-myc protein and to a transient decrease in c-myc mRNA level. However, implication of RNase H in this process could not be demonstrated.