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Somagenics Awarded NIH Grant to Develop Targeted microRNA Detection Tech


NEW YORK (GenomeWeb) – Bolstering its efforts to develop a suite of technologies for microRNA detection, Somagenics this month received a two-year grant from the National Institutes of Health to advance a next-generation sequencing (NGS) approach for the targeted quantification of miRNAs in circulation.

Somagenics is also pressing ahead with a number of complementary tools including a read-suppression technology for which the firm is in negotiations with potential commercialization partners, according to CEO Brian Johnston.

Though it has ongoing projects in the RNAi therapeutics field, Somagenics has long been interested in miRNA detection for biomarker applications. Efforts in this space include miR-ID and miR-Direct, which use novel RT-qPCR techniques to detect the small non-coding RNAs in histology specimens or blood, respectively.

Work on these technologies continues, Johnston said. However, "the field is gradually moving from being based primarily on RT-PCR to being based more on sequencing," which is increasingly viewed as "the best tool for discovering candidate biomarkers."

RT-qPCR, he added, remains a top option for validating biomarkers, as well as using them diagnostically.

In response to the growing interest in NGS, Somagenics is developing a platform called miR-Seq, which involves targeted sequencing of rare extracellular miRNAs ordinarily represented by low numbers of reads and therefore are hard to detect.

Sequence libraries are constructed by ligating adapters to small fragments of RNA or DNA, Johnston explained. "If the ligation is not efficient, for example ,if the piece of RNA folds back on itself and makes the end not very available to ligation, that RNA will be underrepresented or not represented to any significant extent. If you're trying to search for biomarkers, it's possible the ideal biomarker will be the one that is not being ligated and therefore is not represented in your library."

By building libraries using novel enzymatic steps that "simplify and increase the sensitivity of ligation reactions," Somagenics hopes to overcome this issue, he said, though he declined to provide specific details about the technology for intellectual property reasons.

As a proof of concept and with the NIH funding, worth $350,000 in the first year, Somagenics aims to use miR-Seq to reliably quantify 119 extracellular miRNAs that have been reported to be abundant in plasma, then use the method to discover and validate miRNAs in plasma that can be used as biomarkers for Parkinson's disease to create a diagnostic assay for the condition.

Meanwhile, Somagenics is continuing work on a targeted miRNA sequencing technology that uses a selection-by-hybridization approach to limit NGS only to sequences of interest.

"We can look at a class of sequences that all have some sequence feature in common and ignore everything else," Johnston said. "That has the advantage …[of being] cheaper because you are not wasting all your reads on irrelevant sequences … [while being] more sensitive because what you are looking at has been presented in a higher amount.

The exact details of this project are also being kept under wraps for now, he said.

But perhaps Somagenics' nearest-term opportunity in the miRNA detection space is a method designed to eliminate highly abundant and extraneous molecules from sequencing reads, Johnston said.

In miRNA biomarker discovery experiments, for example, a few miRNAs may account for as much as 90 percent of total miRNAs in a particular cell type, he said. "Consequently, to look at the other 10 percent you have to sequence 10 times more of a sample," which is correspondingly more expensive.

Like existing products do for ribosomal RNA, Somagenics' method suppresses non-target miRNAs in NGS reads — although it does so in a different manner, Johnston added.

While miR-Seq, miR-Direct, and Somagenics' other projects are steadily moving ahead, "the read-suppression technology is ready to go," he said. "We're in discussions with a couple of potential commercialization partners to get that and the other techniques to the market."