SYNTHETIC ANTISENSE OLIGONUCLEOTIDES - PRINCIPLES AND ANTILEUKEMIC ACTIVITY

Inhibition of gene expression by antisense oligonucleotides relies on the ability of an ODN to bind a complementary messenger RNA sequence a nd prevent translation of the mRNA. Most human follicular B cell lymph omas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulatio n of the BCL-2 protein expression, endowing cells with survival advant age. The capacity of oligonucleotides to modulate gene expression spec ifically has been exploited to down regulate the overexpression of BCL -2 protein in the SU-DHL-4 human follicular B cell lymphoma line by ta rgeting the hybrid transcript with ODN encompassing the unique nucleot ide sequence in the fusion region.