LIPOSOMAL DELIVERY OF OLIGODEOXYNUCLEOTIDES

We have previously demonstrated that liposome-incorporated methylphosp honate antisense oligodeoxynucleotides (oligos) specific for BCR-ABL c an selectively inhibit the expression of p210(Bcr-Abl) protein and the proliferation of chronic myelogenous leukemia cells in vitro. Here, w e show that liposome-entrapment of phosphodiester and phosphorothioate oligos specific for BCR-ABL can also selectively inhibit the prolifer ation of chronic myelogenous leukemia cells. We have studied the intra cellular localization of liposomes by fluorescent microscopy and found that liposomes are readily taken up by leukemic cells and are localiz ed in the cytoplasm, allowing increased access of oligos to target cel ls intracellularly. Liposomal oligos are not toxic to peripheral blood mononuclear cells nor to bone marrow progenitors isolated from normal hematological donors. These studies strongly suggest that liposomal d elivery of oligos may indeed circumvent the major limitations that pre clude the clinical development of antisense oligos.