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DNAe Plans to Target Infectious Disease Market with Genotyping, Sequencing Combo Platform

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NEW YORK (GenomeWeb) – London-based DNA Electronics is developing a point-of-care diagnostic platform that can amplify, genotype via real-time PCR, and do targeted semiconductor sequencing all on one chip. Initially, DNAe will target the infectious disease market and plans to bring its platform and its first product — a bloodstream infection test — through US Food and Drug Administration clearance, Clinical Sequencing News has learned.

The company recently underwent a number of changes, including transitioning its technology to combine amplification, genotyping, and sequencing; narrowing the scope of its sequencing from chips that can sequence megabases to chips that sequence just a handful of genes; and hiring a management team to take it through commercialization. Recent management hires include Steve Allen as chief operating officer and Nick McCook as chief business officer.

Last year, the company secured an undisclosed amount of funding from the Genting Group and its founders and this year it opened a second office in Washington, DC. The company currently has a staff of 62, including 46 scientists and engineers.

DNAe holds patents on pH-based semiconductor sequencing and it licenses the technology nonexclusively to Thermo Fisher's Ion Torrent. Previously, DNAe was also collaborating with Roche to develop a semiconductor sequencing platform that would compete with the Ion Torrent, but that collaboration ended when Roche shut down those R&D efforts last year.

After the deal with Roche ended, the company decided to refocus its efforts on targeted sequencing, since it still owned intellectual property in the area that it had not licensed, CEO Chris Toumazou told CSN. Specifically, DNAe decided to tackle infectious diseases — an area that could benefit from faster, more sensitive diagnostics.

"That is one application where you really need to go from blood to result in two to three hours as opposed to 48 hours," Toumazou said.

Current molecular approaches to infectious disease testing include mass spectrometry, which "is great for working out what the pathogens are" but first require blood to be cultured; and multiplex PCR tests that "can't really detect more than a handful of pathogens simultaneously," DNAe Chief Operating Officer Steve Allen told CSN. Next-generation sequencing has the advantage of taking an unbiased approach to pathogen detection but is limited by its "sheer scale, cost, and run times," Allen said.

"By being able to combine PCR and genotyping, and then going on to sequence in a targeted way," Allen said, "you can very quickly get the bacterial species, the bacterial strain, and the antimicrobial genes for 30 to 40 bugs simultaneously."

The company is designing the chip to directly analyze whole blood samples and provide a result in two to three hours. The platform will first perform sample prep including enriching bacteria, lysing cells, and purifying DNA, followed by on-chip amplification to identify the bacteria, genotyping to figure out the specific strain, and sequencing to identify any antimicrobial resistance genes.

Last year, DNAe described its on-chip amplification technique in a study published in Nature Methods. In that study, the team tested two different methods of amplification — PCR and isothermal amplification. For both, the researchers relied on monitoring pH signatures to confirm that amplification took place.

Toumazou said that the basics of that publication are the same as what will be incorporated into the final product, except that previously, the team was targeting a chip that would be able to sequence panels of 20 megabases to 100 megabases, but is now aiming for even lower throughput. Sequencing will include "unique sequences in pathogen genomes" that will serve as identifiers, as well as antimicrobial resistance genes.

Already, DNAe has designed a genotyping platform that performs on-chip amplification and RT-PCR for genotyping, which it sells to GeneU, a cosmetic firm that personalizes anti-aging skin care products. That product is a bit smaller than a USB stick.

The new chip, which will include sequencing capabilities, will be slightly larger than that and will work with a small portable instrument that will process several milliliters of blood.

The system will be programmable and configurable, Toumazou said. The offering is almost like a "mini-computer," he said, so the user can program it for amplification, genotyping, or sequencing, as desired, and all steps will be performed on the chip.

Allen said that DNAe plans to bring the platform, initially with a bloodstream infection test, through FDA clearance, and said that the company has "clear guidance from FDA about how to go about clinical trials" through the agency's recent guidelines on multiplexed, DNA-based microbiology diagnostics.

He added that the company will be in product development for another 15 months, and would begin the clinical trial in 2016, which he anticipated would last around six months.

One challenge of doing a clinical trial with a multi-analyte test is that "potentially some of the pathogens may be at very low levels, so you need many samples to get proper statistical significance," he said.

He said the company plans to include 1,500 clinical samples in its trial, and will follow the FDA guidance for highly multiplexedin vitro diagnostic assays that allow rare analytes to be spiked into clinical samples to get an accurate estimate of the test's sensitivity.

Prior to obtaining FDA approval, "there's the potential of using the product in the research environment," he added.

The company is aiming for panels that cost in the range of $100 to $200, although it has not yet set a price for the platform itself.

Aside from bloodstream infections, the company plans to develop a portfolio of products in infectious disease and oncology, Allen said.