IN-VITRO INHIBITION OF THE PIM-1 PROTOONCOGENE BY CHIMERIC OLIGODEOXYRIBONUCLEOTIDES COMPOSED OF ALPHA-ANOMERIC AND BETA-ANOMERIC FRAGMENTS

We show that oligodeoxyribonucleotides (oligos) composed of alpha- and beta-anomeric sections can be used as antisense compounds. An octamer has been chosen as an effector domain to form a substrate for RNaseH. This octamer is complementary to the translation start site of the pi m-1 protooncogene mRNA. Chimeric alpha-beta oligos and their beta-anal ogs have a similar binding affinity for their target. These oligos als o direct efficient RNaseH-mediated cleavage of target mRNA. Among all alpha-beta oligos studied, one with an alpha-fragment bound by its 3'- end to the 3'-end of the beta-octamer is the most resistant to nucleol ytic digestion in biological media. The alpha-beta oligos have been fo und to inhibit in vitro translation of pim-1 RNA with specificity.