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Start-Up Creating a Simpler, Stable Liquid Biopsy

Blood vials

(Ahmad Ardity, Pixabay)

3 June 2020. A new company spun off from University of Oxford is developing a stable and sensitive blood test to detect multiple types of cancer in their early stages. Base Genomics in Oxford, U.K. is also raising £9 million ($US 11 million) in its seed funding round.

Base Genomics, officially launching today, applies epigenetics, the study of inherited changes in gene expression from outside the basic DNA sequence, to cancer diagnostics. An emerging form of cancer detection tests blood samples for fragments of tumors that break off from the tumor, known as circulating tumor cells. These liquid biopsies with blood draws are much easier to perform than tissue biopsies requiring surgery, and can be done more frequently to track progress of the cancer and molecular changes in the tumor.

A more recent upgrade in liquid biopsies is adding DNA methylation, an epigenetic process to detect and analyze circulating tumor cells. DNA methylation is a test for changes in the DNA chemistry, looking for modifications expressed in two specific compounds derived from cytosine, one of the base nucleic acids in DNA. Measuring various levels of these two chemicals in DNA can serve as indicators of specific types of cancer, making it possible for liquid biopsies to track changes in the tumor’s chemistry, and provide more precise targets for therapies.

DNA methylation, however, has its limitations. A notable drawback in these methods up to now is the need to pre-treat DNA samples with bisulfites. These compounds are harsh chemicals that can damage the DNA, a critical problem when working with small quantities of circulating DNA in blood samples. The damage to DNA also results in imbalances in genomes leading to analytical errors and higher sequencing costs.

Researchers from Ludwig Institute for Cancer Research, affiliated with Oxford, devised a process called TET-assisted pyridine borane sequencing or TAPS that they say avoids bisulfites and their difficulties. TET stands for ten eleven translocation, a class of human enzymes that oxidize the two cytosine-derived compounds assessed in DNA methylation. In a February 2019 paper published in Nature Biotechnology, a Ludwig Institute team and others describe the process and lab tests showing TAPS does not harm DNA, yet still detects changes in DNA with high sensitivity and specificity.

Two of the paper’s authors from Ludwig Institute were Yibin Liu and Chunxiao Song, co-founders of Base Genomics, with Oliver Waterhouse, a former entrepreneur in residence at Oxford. Base Genomics is developing a DNA methylation-based blood test for early cancer detection and tracking of the disease in patients. The company says their process delivers higher quality results, with greater efficiency, and lower sequencing costs. Waterhouse is serving as Base Genomics’ CEO, while Liu is the company’s lead chemist and Song serves as an adviser.

Base Genomics recruited Oxford cancer specialist and molecular diagnostics researcher Anna Schuh, as its chief medical officer. “In order to realize the potential of liquid biopsies for clinically meaningful diagnosis and monitoring,” says Schuh in a company statement, “sensitive detection and precise quantification of circulating tumor DNA is paramount. Current approaches are not fit for purpose to achieve this, but Base Genomics has developed a game-changing technology which has the potential to make the sensitivity of liquid biopsies a problem of the past.”

The seed financing round is led by Oxford Sciences Innovation, an affiliate of the university that invests in new technologies from university labs and advises entrepreneurial scientists in company formation and commercializing their discoveries.

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