License to drive

ST. LOUIS—With a boost from technology developed at King'sCollege London, Sigma Life Science, the biological products and servicesresearch business of Sigma-Aldrich, is developing and commercializing a testthat facilitates the simple, accurate identification and validation of microRNA(miRNA) targets.

The test is intended to ease research bottlenecks commonlyexperienced in the identification of targets of miRNA, gene-expressionregulators in eukaryotic cells. Aberrant expression of miRNAs are known to playa role in many disease states—making them important targets for clinicalresearch in oncology, wound healing and infectious disease—but the specifictargets of most miRNAs are unknown.

"Because of the promiscuous nature of microRNA/targetbinding, a number of targets can be identified for an individual microRNA,"says a spokesman for King's CollegeLondon Business, the university's innovation arm. "These would further beinvestigated for their involvement in disease pathogenesis and possible drugtargets."

But according to King's College London and Sigma LifeScience, 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 miRNAand other non-coding RNAs is figuring out what genes they are regulating," saysSteven Suchyta, market segment manager for Sigma Life Science's emergingtechnologies division. "miRNAs are not very specific. One miRNA can targethundreds or thousands of different genes. To investigate this, people aretrying to use computer algorithms, but these are unreliable because the rulesare so undefined, and you can't validate the results. We knew we needed to finda better way of functionally figuring out what gene an miRNA is regulating."

To overcome these challenges, scientists in the university'sDivision of Cancer Studies developed a technology that enables thestraightforward identification of target genes that are strongly regulated by agiven 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 whichSigma could use to transfect into new cells lines and test for miRNA expressionas well as cell lines already transfected with the 3' library proprietary tothe university.

"This enabled evaluations by Sigma of the technologies'performance characteristics, the scope to assemble the King's College's technology into aformat amenable for routine use by research labs and the ability to take theKing's technology and evolve it into a format that was amenable forlarger-scale production in a cost-effective manner," the college's spokesman says.

Through an exclusive license deal, Sigma Life Science willcommercially develop the product as the Mission Target ID Library Workflow foruse by laboratory researchers. The agreement, the financial terms of which werenot disclosed, is in line with Sigma Life Sciences' "commitment to releasinginnovative products that help with miRNA research and providing tools for themiRNA and non-coding RNA workflow," says Suchyta.

There are four transfection steps that researchers will findeasier 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 commercialdevelopment experience was invaluable in the development of this process.

"Sigma's experience in seeing life science technologiestaken to market meant they possessed an experience and vision which accuratelyunderstood the market demands for research tools that could be based on theKing's College's technology," says the spokesman. "This experience also brought with it anunderstanding of what user format of research tool could be constructed usingthe King's College's technology as its foundation. Their experience in development ofsuch user-formats ensured they would establish efficiently how to ensureperformance characteristics for the tool would be achieved to the levelrequired by users, and importantly, the efficient development steps that wouldbe required to evolve the King's College's technology into a high-performance format thatwas still amenable to large-scale production and supply in a cost-effectivemanner."

Ultimately, says Dr. Joop Gaken, a lead researcher in King'sCollege's role in the project, the new test has serious implications foroncology research.

"The role of miRNAs in cancer is well established, andseveral miRNAs clearly function as either oncogenes or tumor suppressor genes,although the target genes are unknown in the majority of cases," Gaken says.