ABSTRACT

This chapter focuses on the uptake and intracellular localization of various modified and unmodified oligodeoxynucleotide (ODN) in primary lymphocytes and myeloid cells. It describes that phosphorothioate ODNs have a much greater affinity for spleen cell membranes than phosphodiester ODNs. The chapter suggests that the possibility that the phosphorothioates might be useful as a gentle way to displace cell membrane-bound phosphodiester ODN. To combine the good RNase H activation and hybridization properties of O-ODNs with some of the nuclease resistance of S- and MP-ODNs, chimeric ODNs modified with several phosphorothioate or methylphosphonate linkages at just the 5' and 3' termini can be used. Leukemic hematopoietic cells are far more sensitive to c-myb antisense ODNs than are normal cells. The level of ODN association in normal cells from leukemic patients was similar to that of the same cell type in normal controls. In acute leukemia, ODN uptake by leukemic cells exceeds that by normal cells.