Silencing gene expression in cancer
Cancer is the second cause of mortality in the Western world. Although some progress in therapy has been made for certain types of cancer, overall prognosis is still poor and innovative treatments are urgently required. The 'Intracellular methylases delivery as therapeutic tool for carcinoma specific regulation of gene expression' (Imedgen) project developed a novel method for treating carcinoma by switching off expression of a carcinoma-associated gene, EpCAM. Partners achieved this by delivering a methylating enzyme, MSssI, which modifies DNA at a particular site (CpG), to the EpCAM gene's promoter region. CpG islands are GC-rich regions at or near the transcriptional start site of a promoter. When genes are expressed these regions are unmethylated. Study results verified the specificity of the system, clearly showing CpG methylation only adjacent to the binding site of the triplex forming oligonucleotide (TFO). Although the system needs to be validated in vitro and in vivo for its efficiency to silence EpCAM, the developed technology is a promising one. Dissemination efforts by the project partners attracted pharmaceutical interest for the approach, which is expected to have a broad spectrum of applications.
