The sequencing of the human genome in 2003 signalled the dawn of an exciting new era for genetic medicine. Yet almost 15 years later it has become clear that our genes alone cannot predict our susceptibility to most complex diseases or fully explain fundamental aspects of human development and ageing.
Most vendors of epigenetic modification proteins and reagents have enhanced and broadened their offerings in recent years. Of particular note is the increasing range of proteins and binding assays that now support research on the Bromodomains and other reader proteins.
During the last few years, advances in the understanding of epigenetic processes have led to an explosion in interest in this area as a potential source of new targets for the discovery of medicines. In addition, development of chemical probes directed toward specific players in histone modification is showing promise as a way to help unravel the highly complex ways in which epigenetic systems impact gene expression.
Although it is still early days in terms of our understanding of epigenetics, the fast development of new tools and technologies to define genome-wide epigenetic variations in humans has the potential to enable effective new epigenetic therapies and diagnostic tests for a wide range of diseases beyond and including cancer.
Heightened awareness of the potential importance of epigenetic targets in many disease areas, and growing vendor interest in developing new assays to screen DNA methylation and histone modifications encouraged HTStec to undertake market research in this area in June 2010. The study concluded epigenetic screening was still very much in its infancy and there was a need for new and improved screening tools and assays. Assay specificity, producing active protein and the availability of good antibodies were all cited as key obstacles. Much attention is coming from oncology areas and interest is particularly high in the assaying histone deacetylases (HDAC & Sirtuins), histone methyltransferases (HKMT & HRMT), histone demethylases (HDM), DNA methyltransferases (DNMT) and histone acetyl transferases (HAT). Epigenetic target assays are increasingly being attempted utilising a wide range of different screening technologies. Some of the more generic approaches currently being developed and validated are suitable for all types of histone substrates, and have application across a diverse range of histone modifications. The breadth of assays becoming available will soon extend well beyond the HDAC & Sirtuins. These approaches now need to be translated into a set of robust readyto- use assay kits or tool-box reagents to open up the epigenetic field to HTS. An increasing number of vendors also now offer fee-for-service screening and profiling against epigenetic targets, such that outsourced compound testing against a panel of epigenetic assays is becoming a real possibility. In conclusion, the tools required to support epigenetic screening are fast emerging as our knowledge and experience with these targets increases, such that we can expect to see greater adoption or external use of these assays by Pharma and Biotech lead discovery programmes over the coming years.