Direct Genomics revives Helicos sequencing system for China’s hospitals

Direct Genomics, a Shenzhen, China-based sequencing company, is mounting a challenge to San Diego-based Illumina and other sequencing giants with a low-cost sequencer for clinical use. Last October, the company launched its GenoCare analyzer, a singlemolecule genome sequencer specifically for clinical applications. Since then, competition in the genomic sequencing spaces has continued to heat up. In January, at the JP Morgan Healthcare conference in San Francisco, Illumina launched the MiniSeq System, an integrated benchtop analyser designed for clinical diagnosis, which will begin shipping the this quarter. And Human Longevity, the San Diego-based company co-founded by J. Craig Venter unveiled its oncology program, a set of products still in development for whole germline, tumor genome and whole cancer exome analysis.

For now, Direct Genomics has set its sights on China. The company is taking advantage of patents licensed from Caltech, using a sequencing method first brought to market by Helicos Biosciences of Cambridge, Massachusetts. Helicos was founded in 2004 by Stephen Quake, who came up with the idea of single-molecule sequencing, though Helicos eventually went bankrupt in 2012. A postdoc in Quake’s laboratory, He Jiankui, now Direct Genomics CEO and a biophysicist and genomics researcher at South University of Science and Technology of China, returned to China and set up his company to build a sequencer geared towards diagnostics. Quake now leads the scientific advisory board for this new company.

Direct Genomics’ instrument is meant only for the clinical market. The GenoCare analyzer enables ‘direct’ reading of raw, unmodified DNA in single molecules. Whereas conventional sequencers require amplification of DNA with PCR and several other steps, the GenoCare analyzer is an amplification-free technology. It intensely focuses light on DNA molecules and prevents illumination of contaminants to allow detection of the tiny signal from a single strand of DNA. Though it cannot match Illumina or Thermo Fisher sequencing platforms on volume in whole-genome sequencing, the technology promises fast and cheap sequencing of critical areas of patient genomes so that doctors can tune in on particular mutations and tailor treatment to patients.I really like it. It takes advantage of sort oftraditional’ sequence by synthesis methods like 454 and Ion and Illumina, but gets to singlemolecule detection,” says Michael Weiner, a sequencing expert and biotech entrepreneur at the life sciences tools provider AxioMx, in Branford, Connecticut.

As whole human genome sequencing descends into the $1,000 range, Direct Genomics intends to offer $100 clinical sequencing—something that He says will bring it under China’s national insurance coverage.Once we drive down the cost, and make it $100, the 1.3 billion Chinese will be able to take clinical sequencing as routine test,” says He. “And the entire process from taking blood to report will be less than 20 hours.

The company has already started an ‘earlyaccess program’ in collaboration with three hospitals, all in Guangdong in southern China. The first targets of its pilot projects are a noninvasive prenatal test for Down’s syndrome and other trisomies (chromosome 21, 13 and 18 trisomies); cancer panel, including 50 cancer genes; and genetic disease panel, including 100 genetic diseases. Such tests can now cost $500 or more. In January, Direct Genomics signed up its first noninvasive prenatal testing customer, Harmonicare Medical of Hong Kong, a holding company for 30 mother and child hospitals.

Sequence providers, potential customers, are in wait-and-watch mode. Ruiqiang Li, CEO of the Beijing-based genomics services provider Novogene, which has one of the few Illumina HiSeq X Ten whole genome sequencing platforms in China, says that by avoiding PCR amplification, singlemolecule sequencing avoids bias, but a high error rate has proved a challenge. “It’s a very important step forward. But we see that Helicos failed, and PacBio and Oxford Nanopore have very high sequencing error rate,” says Li.However, we are interested, and hope to see the commercial launch of the instrument.”

Direct Genomics’ He says they are working to correct such problems. “We compensate the errors by sequencing the DNA over 1,000 times,” says He. Their error rate is then close to Illumina and Thermo Fisher sequencers, says He, referring to results ( 2015, doi:10.1101/029686) from sequencing cancer genes and hepatitis B virus, in which fivefold sequencing produced accuracy of 100%.

China’s sequencing providers are gearing up to launch a precision medicine program that is rumored to have a budget of RMB60 billion ($9.1 billion) over the next 15 years (Nature 528, 9–10, 2016). It is expected to be announced officially this spring, and major hospitals around the country are quickly assembling precision medicine centers.

He estimates that Chinese patients will be getting 20 million noninvasive prenatal diagnosis, 3 million cancer panels, 20 million genetic disease tests, 30 million cancer early diagnosis tests and 10 million hepatitis B virus tests annually. He hopes to sequence just under half with GenoCare.

Since its establishment in 2013, Direct Genomics has raised RMB120 million ($18.3 million) through three rounds of investment and government funding. Then, in a series C fundraising closed in December, a medical device company invested another RMB200 million ($30.4 million). He hopes to gain China Food and Drug Administration approval, through China’s green-light channel, in 2017.

Will narrowing the market to clinical use work? “It still isn’t a way to routinely or practically sequence the whole genome, so it’s only going to be for a limited market,” says Weiner.For resequencing, I’m not sure they are much cheaper than Illumina and the cost of their instrument and the way it’s performed means it isn’t quite as multiplexable.” But, Weiner says, “It could work where labor costs are reduced. It would be able to fill a niche in a rather large resequencing market.” He sees his company as a third-generation sequencing provider and hence not in direct competition with already established outfits. “Our threat comes from nanopore sequencing technology, such as [those from] Genia (a Roche company) and Oxford Nanopore.”

Sequence providers are happy to have more options. “In all, it’s a hot area,” says Li.Thermo/Life Tech, Illumina, PacBio, Qiagen all launched new sequencing instruments. We hope to see more technologies, so that users can choose the right one for specific clinical applications.”