Genomeweb: Genomill Health Positioning Geno1 Technology to Improve Liquid Biopsy Sequencing

 NEW YORK – After closing an investment round last month for an undisclosed sum, Finnish firm Genomill Health is aiming to broaden adoption of its Geno1 technology, a barcoding-based method that it believes can enhance sequencing accuracy and lower costs and turnaround time for applications with high sensitivity and efficiency demands like liquid biopsy. 

The concepts behind Geno1 were developed as part of research initiated at the Massachusetts Institute of Technology and then continued at ETH Zurich by the company’s chief technology officer Manu Tamminen. 

Although Genomill is now focused on advancing the technology for liquid biopsy applications (and potentially other analogous areas like NIPT), Tamminen’s initial work was focused on infectious disease, including a project funded by the Bill & Melinda Gates Foundation. 

“[That project] had to do with the quantification of antibiotic resistance genes from a large number of samples. There are thousands and thousands of antibiotic resistance genes and somehow we would have to quantify them all in a big number of samples,” Tamminen explained. 

“It’s a molecular quantification problem and something which is completely intractable by common means like qPCR for instance, because of scalability issues. So, we developed this very lean, simplified, minimalistic lab workflow coupling molecular detection with next-generation sequencing and unique molecular identifiers to enumerate those individual molecules.” 

This was a starting point for an interest in liquid biopsies, he added “because [I could see that] we are dealing with very similar [challenges].” 

Although sequencing has become progressively more accurate and less costly, precisely detecting and quantifying mutations in circulating DNA is currently still laborious and expensive, Kalle Koskinen, the firm’s CEO argued. 

“We know the … market is basically struggling with three main hurdles, I would argue: it’s the price, it’s the precision, but it’s also the pace.” he said. With Geno1, Genomill believes it can address all three. 

As described in a European patent application, Tamminen’s approach, developed initially for his antibiotic resistance gene sequencing efforts, involves a multiplexed ligation method, which “aims to combine the simplicity and parallel potential of … barcoding-MLPA with the accuracy and sensitivity of qPCR.” 

In brief, the method expands on legacy methods, like multiplex ligation-dependent probe assays, to provide a “very simplified lab workflow for quantification of scarce targets,” Tamminen said. 

As in traditional MLPA, the approach involves designing probes that bind side by side to the targets one wants to detect or quantify and then ligating them together. In addition, the probes have overhangs, which have “universal parts that you can then use for PCR amplification or some other kind of amplification.” 

In the traditional MLPA, “you would just separate those in a gel so that different lengths correspond to different molecular targets,” he added. “But what we figured out was that you could actually add random ends to the overhangs and thus get molecular barcodes because each ligation event is unique. You get a unique molecular identifier from the pool of those random ends for each molecule. And then you can use the other overhang for, for instance, patient-specific sample barcoding.” 

The concepts at work have all “been there before,” Tamminen admitted. “For instance, the probe ligation or extension plus ligation, that’s part of MLPA. And you get unique molecular identifiers, for instance, in RNA-seq … and then you have things like sample barcodes as a standard part of the Illumina sample prep workflow.” 

But combining all of these technologies in a liquid biopsy workflow is ’’”new, he added. 

Genomill actually began as a clinical genomic services company, offering local access to NIPT, liquid biopsy, and other tests, like Color’s hereditary cancer risk panel. But after being pushed out of local markets by a larger player in recent years, the company happened upon Tamminen’s work, and refocused on its development. 

Although neither Tamminen nor the company have published anything yet on Geno1 (a report from the Gates foundation pathogen resistance gene testing effort is in the works) Koskinen said that the firm has conducted internal calculations, estimating that the method might be able to lower NGS liquid biopsy production costs by as much as 80 percent, and accuracy by something in the realm of 30 percent. 

In terms of turnaround time, “once you have already isolated the DNA, then it comes to a couple of hours [for] our technology in comparison with several days with other technologies,” he added. 

After announcing its investment round last month — in which Finnish investment firms Voima Ventures and Outpatient Care Research Foundation participated — Koskinen said that the company is now focused on expanding usership of Geno1, which is currently being piloted by “one of the bigger players in Switzerland.” 

The company hopes to eventually license the technology to liquid biopsy test developers and pharma companies using liquid biopsy in drug and companion diagnostic development. 

The methodology itself is platform agnostic in terms of sequencing. 

Perhaps encouragingly for the firm, other molecular quantification and counting methods that propose to lower the costs of sequencing seem to have been making strides in adoption recently, for example Singular Biotechnology’s multiplex ligation-dependent probe amplification approach, which prompted a recent acquisition of the firm by Invitae. 

Tamminen said that the firm got the first review of its patent application for Geno1 back from the European Patent office about a year and half ago, which “looked very positive.” 

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