Figure 3.

Cancer therapies based on antisense oligonucleotide-mediated splicing modulation. (a) Treatment of cancer cells with an ASO masking the proximal 5' splice site effectively switches BCL-X splicing and induces apoptosis. (b) MDM4 protein is highly expressed in embryonic tissues and in cancers as a result of enhanced exon 6 inclusion, driven mainly by SRSF3. ASO-promoting skipping of exon 6 is a suitable approach to inhibit p53 degradation by MDM4 in cancer cells. (c) Example of the hypothetical application of ASO therapy to FAS. An ASO masking the PTBP1-binding site in FAS exon 6 could be rescue FAS exon 6 inclusion, thus enhancing FAS-mediated cell death of cancer cells