Mirus Bio said this week that it has won a two-year, $900,000 grant from the National Institute of General Medical Sciences to improve its microRNA labeling technology for clinical research.
The grant will also support the company’s exploration of whether the labeling technology, called Label IT, can be used for diagnostic applications.
While Mirus has been marketing Label IT miRNA kits for microarray studies since late 2005, the technology has been limited to basic research.
“What we want to do is move into the world of real clinical samples,” Rich Schifreen, vice president of research products at Mirus, told RNAi News this week. But “we think there is a lot of work to do to translate where we are now into a practical method for looking at clinical specimens.”
According to Mirus, the Label IT technology comprises “a reactive alkylating agent with strong nucleic acid-binding capability facilitated [by] electrostatic interactions. Labeling via covalent modification … of RNA, including miRNA, or DNA can take place on reactive heteroatoms on any nucleotide of the nucleic acid polymer.”
In earlier NIH-funded work, Mirus compared Label IT to enzymatic miRNA-labeling technologies and found that direct chemical labeling of the small microRNA species “worked really well,” but that the profiles generated by different enzymatic labeling methods were “distinctly different,” Mary-Anne Watt, a Mirus researcher and principal investigator on the NIGMS grant, said.
“We looked a little further into those discrepancies and noticed that enzymatic labeling based on poly A polymerase … missed some microRNA-based species that were present in the sample,” she said.
“When one method sees something and another method doesn’t, there is a question [of whether] one [method] is missing it or the other method is seeing something that isn’t there,” Schifreen added. “We went through an exhaustive process … to look at these same samples and same microRNAs to verify that the Label IT method was detecting all the microRNAs present that were being missed by enzymatic labeling.”
The grant announced this week will help Mirus follow up on those previous experiments in order to optimize Label IT as a chemical labeling method for microarray-based miRNA expression profiling analysis, according to Watt.
With the NIGMS funding, Mirus will “follow up on those [earlier] observations to look at the predominance of the false negatives in microRNA expression profiling using enzymatic methods,” she said. This will be done on “a much more global scale across the microRNAs in a particular species and sample, and [involving] much more statistical analysis.”
The grant project also seeks to move the research “into more of a clinical avenue” by optimizing the Label IT technology for direct labeling of microRNA samples from clinical specimens, especially those available only in limited amounts, she said.
“The initial work we did was with biopsy materials from animals, and these are large samples, they’re fresh samples,” Schifreen explained. “When dealing with samples that would be obtainable for clinical research … we’re talking smaller samples and perhaps [ones] that have been preserved in some way.”
Importantly, the new grant work will examine whether the Label IT technology has the potential for use in a diagnostic setting.
“Our hope is that, as part of this grant, we will identify some diagnostically useful and important biomarkers that we can go on to develop as diagnostic tests,” Schifreen said.
Assisting Mirus in this effort is Gregory Tsongalis, director of molecular pathology at the Dartmouth Hitchcock Medical Center, who will provide Mirus with samples for analysis and act as a consultant.
“What we want to do is move into the world of real clinical samples. [But] we think there is a lot of work to do to translate where we are now into a practical method for looking at clinical specimens.”
“We’re looking for [Tsongalis] to give us guidance — not only giving us samples, but selecting the right samples, selecting the right assay strategies, and ultimately being able to help us do an early validation of utility,” Schifreen said. “He can focus us toward doing this work with the kind of samples that will provide useful clinical discovery.”
Even if the Label IT technology proves robust enough for diagnostic applications, it remains unclear whether Mirus would step onto the miRNA diagnostic field itself, or whether it would find a partner to take the technology in this direction.
Already, a number of companies have begun positioning themselves as key players in miRNA diagnostics including Rosetta Genomics, Asuragen, Stratagene, US Genomics, and Exiqon.
“A big question that we have, and I think everyone has, is, ‘Ultimately, what is the useful tool going to be?’” Schifreen said. “Is it going to be a single test? Perhaps [it will] focus in on a particular microRNA or particular small group of microRNAs that would be tested one or two or three at a time. Or perhaps you need to do a microarray profile and look at differences in expression of large numbers of microRNAs.
“Right now we don’t know, [and] we don’t know ultimately what a product would look like,” he said. “So we don’t know whether it is something we’d do by ourselves, whether we would look for partners, or [whether we’d pursue] a licensing arrangement with another company.
“Until we have a better idea of where we’re going, it’s pretty hard to say” how Mirus will play in the miRNA diagnostics field, Schifreen added. “We’re open right now.”