CATIONIC LIPIDE MEDIATED TRANSFER OF C-ABL AND BCR ANTISENSE OLIGONUCLEOTIDES TO IMMATURE NORMAL MYELOID CELLS - UPTAKE, BIOLOGICAL EFFECTSAND MODULATION OF GENE-EXPRESSION

Uptake and biochemical and biological effects of antisense oligodeoxyn ucleotides (ODN) specific for c-abl and bcr genes were studied in norm al immature myeloid cells. CD34-positive cells were purified by positi ve and negative selection and cultured in liquid culture for 7 days. T hese cells were then incubated with ODN, either alone or in combinatio n with cationic lipids. The uptake of ODNs was enhanced by the use of cationic lipids. In addition, very low concentrations of ODNs in combi nation with cationic lipids were capable of specifically inhibiting th e expression of the c-abl gene. In contrast, no effects were seen on t he expression of bcr. However, despite the effective blocking of c-abl e expression, no changes in cellular growth patterns were observed in liquid culture or in a colony-forming assay. We conclude that the use of cationic lipids might enhance the gene-regulatory effects of ODNs b y increasing their uptake into normal hematopoietic cells.