INHIBITION OF LEUKEMIA-CELL PROLIFERATION BY FOLIC-ACID POLYLYSINE-MEDIATED INTRODUCTION OF C-MYB ANTISENSE OLIGODEOXYNUCLEOTIDES INTO HL-60 CELLS

The inhibitory effect of c-myb antisense oligodeoxynucleotides (ODNs) conjugated to folic acid (FA) on HL-60 cell proliferation was examined . Folic acid was covalently linked to a polylysine chain and purified by gel chromatography. Sterile FA-polylysine was complexed with c-myb sense and antisense. Exposure of HL-60 cells to the FA-polylysine-c-my b antisense ODN complex resulted in a down-regulation of c-myb express ion and a greater inhibition of proliferation than that obtained using free ODNs. Moreover, FA-polylysine conjugate alone or complexed to c- myb sense ODN was not toxic to cells. The antigenic properties and upt ake of the vitamin were not affected by the polylysine chain. These da ta suggest that this strategy is potentially useful for the selective delivery of anti-oncogene-targeted ODNs into cancer cells.