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 and prevent translation of the mRNA. Most human follicular B cell lymphomas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulation of the BCL-2 protein expression, endowing cells with survival advantage. The capacity of oligonucleotides to modulate gene expression specifically has been exploited to down regulate the overexpression of BCL-2 protein in the SU-DHL-4 human follicular B cell lymphoma line by targeting the hybrid transcript with ODN encompassing the unique nucleotide sequence in the fusion region.