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ST. LOUIS—With a boost from technology developed at King's College London, Sigma Life Science, the biological products and services research business of Sigma-Aldrich, is developing and commercializing a test that facilitates the simple, accurate identification and validation of microRNA (miRNA) targets.
The test is intended to ease research bottlenecks commonly experienced in the identification of targets of miRNA, gene-expression regulators in eukaryotic cells. Aberrant expression of miRNAs are known to play a role in many disease states—making them important targets for clinical research in oncology, wound healing and infectious disease—but the specific targets of most miRNAs are unknown.
"Because of the promiscuous nature of microRNA/target binding, a number of targets can be identified for an individual microRNA," says a spokesman for King's College London Business, the university's innovation arm. "These would further be investigated for their involvement in disease pathogenesis and possible drug targets."
But according to King's College London and Sigma Life Science, the identification of miRNA targets is laborious and inefficient, relying on computer algorithms and subsequent validation by in-vitro assays.
"One of the problems that people face when studying miRNA and other non-coding RNAs is figuring out what genes they are regulating," says Steven Suchyta, market segment manager for Sigma Life Science's emerging technologies division. "miRNAs are not very specific. One miRNA can target hundreds or thousands of different genes. To investigate this, people are trying to use computer algorithms, but these are unreliable because the rules are so undefined, and you can't validate the results. We knew we needed to find a better way of functionally figuring out what gene an miRNA is regulating."
To overcome these challenges, scientists in the university's Division of Cancer Studies developed a technology that enables the straightforward identification of target genes that are strongly regulated by a given miRNA, helping to elucidate important gene regulation events in vivo.
In the early phases of their working relationship, King's College London was able to produce both 3' UTR libraries which Sigma could use to transfect into new cells lines and test for miRNA expression as well as cell lines already transfected with the 3' library proprietary to the university.
"This enabled evaluations by Sigma of the technologies' performance characteristics, the scope to assemble the King's College's technology into a format amenable for routine use by research labs and the ability to take the King's technology and evolve it into a format that was amenable for larger-scale production in a cost-effective manner," the college's spokesman says.
Through an exclusive license deal, Sigma Life Science will commercially develop the product as the Mission Target ID Library Workflow for use by laboratory researchers. The agreement, the financial terms of which were not disclosed, is in line with Sigma Life Sciences' "commitment to releasing innovative products that help with miRNA research and providing tools for the miRNA and non-coding RNA workflow," says Suchyta.
There are four transfection steps that researchers will find easier to navigate, he explains: Zeocin selection, miRNA transfection, Ganciclovir selection and PCR and sequencing.
According to King's College's spokesman, Sigma Life Science's commercial development experience was invaluable in the development of this process.
"Sigma's experience in seeing life science technologies taken to market meant they possessed an experience and vision which accurately understood the market demands for research tools that could be based on the King's College's technology," says the spokesman. "This experience also brought with it an understanding of what user format of research tool could be constructed using the King's College's technology as its foundation. Their experience in development of such user-formats ensured they would establish efficiently how to ensure performance characteristics for the tool would be achieved to the level required by users, and importantly, the efficient development steps that would be required to evolve the King's College's technology into a high-performance format that was still amenable to large-scale production and supply in a cost-effective manner."
Ultimately, says Dr. Joop Gaken, a lead researcher in King's College's role in the project, the new test has serious implications for oncology research.
"The role of miRNAs in cancer is well established, and several miRNAs clearly function as either oncogenes or tumor suppressor genes, although the target genes are unknown in the majority of cases," Gaken says.