Sequencing the epigenetic code of DNA

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Research in the Department of Chemistry on a method for sequencing ‘epigenetic’ DNA modifications led to the spin-out company Cambridge Epigenetix, which is pioneering the development and application of novel epigenetics-based diagnostics and therapeutics.

Epigenetic modifications are ‘marks’ on the DNA that are inherited through generations and play a role in physiological and pathological conditions. The two most common epigenetic modifications are 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). However, the study of their role was hindered by the lack of any quantitatively accurate approaches for characterising them.

Shankar Balasubramanian had already developed the world’s most powerful next generation sequencing technology, Solexa Sequencing, which has revolutionised the field of genomics, when he teamed up with Wolf Reik (Babraham Institute, Cambridge) to develop sequencing techniques that could accurately detect epigenetic modifications.

Exploratory research carried out by Balasubramanian led to the development of oxidative bisulfite sequencing (OxBS-seq), which allowed for the first time the detection of both 5mC and 5hmC to single-base resolution at a crucial period when the significance of epigenetics in health and disease was becoming apparent.

The discovery led to the spin-out company, Cambridge Epigenetix, which has made the technology commercially available worldwide. In 2019, Cambridge Epigenetix launched a discovery and development programme for an epigenetic test to detect colorectal and other cancers from a simple liquid biopsy to analyse circulating free DNA in the blood stream. As of early 2020, the company had raised £40 million in pre-revenue funding and currently employs around 35 staff in the UK.