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Startup Cambridge Epigenetix to Commercialize oxBS Technology


This article was originally published May 17.

Startup firm Cambridge Epigenetix plans to commercialize an epigenetic sequencing technique, with the launch of its first product — called TrueMethyl — expected in August.

The company is a spinout from Shankar Balasubramanian's laboratory at the University of Cambridge. The TrueMethyl kit it is developing utilizes a targeted sequencing approach for quantifying two epigenetic modifications: 5-methylcytosine and 5-hydroxymethylcytosine.

Cambridge Epigenetix was founded in the summer of 2012 and consists of five employees, three of whom are full time. The company plans to focus on epigenetic products that will enable analysis across any sequencing platform or arrays, Jason Mellad, the business development manager, told In Sequence.

The firm's initial product, the TrueMethyl kit is based on a technique called oxidative bisulfite sequencing, or oxBS-seq, which was developed last year by researchers in Balasubramanian's lab (IS 3/1/2012).

The advantage of the technique is that it can measure both methylated cytosine and hydroxymethylated cytosine, said Mellad, whereas conventional bisulfite sequencing cannot distinguish between the two.

Conventional bisulfite sequencing converts unmodified cytosine bases to uracil, leaving methylated and hydroxymethylated cytosines unchanged.

By contrast, oxBS-seq involves two steps to both directly measure methylated cytosines and to infer hydroxymethylated cytosines. In one, it leaves methylated cytosine unchanged, but converts hydroxymethylated cytosine and unmodified cytosine into uracil, enabling the direct detection of 5mC. The second step involves traditional bisulfite sequencing to detect both 5mC and 5hmC. By comparing the two, hydroxymethylation can be deduced.

Since the initial publication of oxBS-seq in Science, researchers have improved the method of DNA purification because the firm discovered that to obtain the best results, DNA had to be of very high quality going into the workflow, Mellad said.

Additionally, the oxidant has been modified. Since publication, the oxidant has "gone through several iterations and we have some key know-how and patent filings covering the improved oxidant, which is much more efficient," Mellad said.

The TrueMethyl kit, which will be broadly available in August, will be available as a six-sample kit for $1,000, a 24-sample kit for $3,000, or a 48-sample kit for $5,000. However, the company will also work with researchers wanting to do more than 48 samples, Mellad said. Each kit includes all the reagents necessary to go from DNA to process the samples for any downstream application, whether sequencing or arrays.

Mellad said initial customers will likely be from academic research labs doing "basic work in epigenetics." Such customers are "looking for a kit that's easy for them to get into their workflow."

Additionally, he said that the company has been approached by several pharmaceutical and biotechnology companies. Sequencing service companies have also expressed interest in working out a deal by which the service providers could license the technology from Cambridge Epigenetix, but Mellad said the company has not yet decided whether to go that route.

Mellad said that the market for epigenetic products and services is growing. "In the past it was niche," he said, "but, that was mainly because of the cost and the tools that were available."

Now, however, "we're increasingly seeing the market growing for people who are for the first time getting into epigenetics research," he added.

Cambridge Epigenetix is not the only one to tap into the growing market. Zymo Research and NXT-Dx are also developing products and services for epigenetics sequencing.

Irvine, Calif.-based Zymo is focusing on methylation sequencing services, offering three different targeted sequencing services that home in on 10 percent, 30 percent, or the whole methylome (IS 3/12/2013).

Belgium-based NXT-Dx, which is based on technology developed by the University of Ghent, is also focusing on the services market, offering genome-wide methylated DNA binding domain, or MBD, sequencing, as well as targeted bisulfite sequencing (IS 9/11/2012).

Additionally, because Cambridge Epigenetix is focused on developing kits, as opposed to services, it will compete with existing techniques.

However, Mellad said that oxBS-seq has an advantage over many of these techniques. "Standard bisulfite sequencing has the limitation in that it doesn't distinguish between the different methylome marks of cytosine," he said. Meantime, other technologies are antibody-based enrichment techniques that have "limitations because of antibody specificity," he said.

He declined to comment on Pacific Biosciences' technology, which makes use of the kinetics of its system to directly measure epigenetic marks without performing a separate experiment (IS 7/3/2012). PacBio users can download software that flags base-modification events.

Currently, the company has 14 customers in its beta trial of the TrueMethyl kit, which it plans to launch broadly in August. Beyond the initial TrueMethyl kit, Mellad said that the company is looking to expand the use of oxBS-seq to be able to evaluate other nucleic acids, like RNA, as well as to develop high-throughput methods of the technique.

Additionally, it is looking to improve on antibody-based approaches for studying epigenetics, such as chromatin immunoprecipitation (ChIP) and methyl-DNA immunoprecipitation (MeDIP). "We're looking at potentially coming up with our own chemical version of that," he said.

Another longer-term goal is to find a way to "link epigenetic data across the board to genomics, proteomics, and transcriptomics," he said. "We believe that you can't look in isolation at one modification. It's all about how things link together."