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Somagenics Looks to Partner microRNA-detection Tech as Therapeutics Efforts Continue

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In an bid to tap a growing interest in using microRNAs as biomarkers of disease or tissue injury, Somagenics has developed a platform for detecting the small, non-coding RNAs in circulation.

Somagenics hopes the platform, called miR-Direct, will attract the attention of an industry partner interested in commercializing it. Meanwhile, the company is continuing to press ahead with its efforts in RNAi therapeutics with a focus on wound healing after pulling back on its hepatitis C program in the wake of advances made by other drugmakers.

The miR-Direct technology is based on an miRNA detection approach known as miR-ID that Somagenics developed several years ago. As described in a 2011 publication, miR-ID involves the “circularization of the miRNA by a ligase; reverse transcription of the circularized miRNA, producing tandem repeats of a DNA sequence complementary to the miRNA; and qPCR amplification of segments of this multimeric cDNA using 5'-overlapping primers and a non-specific dye.”

Although Somagenics had initially been optimizing miR-ID for use in formalin-fixed, paraffin-embedded tissue samples, the company recognized a desire for using circulating miRNAs as clinical biomarkers and therefore began building out a means for using its miRNA detection technology with miRNAs obtained in plasma or serum, Somagenics CEO Brian Johnston told Gene Silencing News.

Unlike the majority of competing technologies for this application, miR-Direct does not require purification of RNA — a variable that produces "uneven results and lost sensitivity," he explained.

The method, which Johnston described last week at the Cambridge Healthtech Institute microRNA as Biomarkers and Diagnostics meeting in Boston, begins with treating plasma or serum with a mixture of reagents that releases target miRNAs from the complexes in which they are contained. This process also protects the miRNAs from nuclease degradation.

Somagenics then introduces a spike in miRNA control, typically using C. elegans RNA that can be easily distinguished from human RNA, so that RNA recovery can be assessed, Johnston said.

The miRNAs are then captured using biotinilated probes, which themselves are captured on streptavidin-coated magnetic beads that can be pulled to the side of the tube. The remaining solution is removed and the beads washed. Lastly, the miRNAs are released from the capture probes in a process that simultaneously circularizes them, leading into the miR-ID process.

At last week's meeting, Johnston presented data from the 2010 paper showing that miR-ID performed on par with TaqMan — currently the preferred technology for miRNA detection — and that it could discriminate miRNA isoforms.

He also showed data demonstrating that miR-Direct can offer increased sensitivity with greater volumes of input plasma without enriching for blood-born enzyme inhibitors, offering the potential to detect low-abundance miRNAs as well as identify smaller changes in abundance.

He noted that Somagenics had also tested whether miR-Direct could work with RT-PCR methods other than miR-ID but said that these results proved "unreliable," likely due to an uncontrolled level of rehybridization to the beads — something that cannot happen with circularized RNA.

With these data in hand, Johnston said he is in the process of looking for a partner that can help bring miR-Direct to the market as part of a broader research tools portfolio that would include the necessary probes and primers.

After commercialization for research applications, he noted that Somagenics would be interested in eventually exploring the diagnostic use of miR-Direct. He added that the company is also looking to extend the use of the technology to RNA fragments including mRNA.

"There is a recognition that assaying mRNAs as potential biomarkers from historical or recently made FFPE blocks is a problem because the process of forming these blocks causes extensive degradation of RNA," he said. "We've adapted the miR-ID method to analyze these fragments of larger RNAs."

Although miR-Direct may be its nearest-term commercial opportunity, Somagenics continues to move forward with its RNAi drug programs, which center on proprietary oligos called short shRNAs, or sshRNAs, that are essentially hairpin molecules shorter than standard shRNAs that do not require Dicer to trigger an RNAi effect.

HCV had long been the company's lead pipeline indication, but the firm decided to not move a candidate into human testing given the high efficacy and oral delivery of newly approved non-RNAi therapies.

As of now, Somagenics considers its work in HCV — which includes three publications in the past 12 months — as proof of concept for the sshRNA technology for other liver diseases that the company might partner on, Johnston said.

As for its next in-house candidate, he said that Somagenics is focusing on wound healing, and that the company is awaiting word on a National Institutes of Health grant application it filed for the funding needed to conduct studies in animal models of diabetic wounds.

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