In particular, acetylation of basic lysine residues in histones – the proteins that DNA binds to form the compact structure of chromatin and, thus, chromosomes – causes the DNA to “unwind” enough to allow gene expression, whereas histone deacetylation causes the chromatin to condense and prevents expression.
Cancer is caused by aberrant gene expression. GeneICE technology “turns off” genes that are over-expressed in cancer by mimicking the natural process of histone deacetylation. This involves a class of enzymes known as histone deacetylases (HDAC). GeneICE compounds consist of a combination of peptides; one binds selectively to the target gene (Bcl-2) and another that recruits the patient’s HDAC enzymes to the gene, silencing it by histone deacetylation. Mis-expression of Bcl-2 has been associated with most cancers and it is currently thought that Bcl-2 is over-expressed in up to 80% of breast cancers, 90% of prostate cancers and 80% of leukaemias. As such the potential market for GeneICE compounds will be significantly large.
The company’s first GeneICE candidate molecule is currently in development to treat prostate cancer that is no longer responding to hormone based treatments.