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Mirus Comparing microRNA Labeling Techs as Product Launch Nears

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In preparation for the launch of a microRNA-specific labeling product, Mirus Bio is currently developing a new labeling technology and comparing it against its existing technology, RNAi News has learned.

Whichever technology proves superior will be introduced sometime in the next couple of months as the company's new microRNA-specific labeling product, according to Jim Hagstrom, vice president of scientific operations at Mirus.

The move to introduce a microRNA-specific labeling technology, Hagstrom noted, comes as part of a broader effort at Mirus to develop a suite of microRNA research products that could be bundled together — specifically a purification product, a labeling product, and a microRNA chip or library that could be placed onto a chip.

The company's existing labeling technology — called Label-It — can be used for labeling both DNA and RNA, including microRNAs, he said. The technology is non-enzymatic, but involves the attachment of various fluorescent molecules to a nucleotide, which is then inserted inside the oligo to be labeled.

This compares with enzymatic labeling approaches, which Hagstrom told RNAi News often involve "adding on a group of nucleotides and through that group … attaching fluorescent molecules. But when you're hybridizing a short piece [of RNA], say a 21-mer, and you're adding more nucleotides, we believe that you're going to end up having hybridization bias, or the potential for hybridization bias."

As such, Mirus' "goal is to take a specific microRNA — the actual molecule — have it purified, and then put a label on it in a location that will not … affect hybridization kinetics," he explained. "When you have a 21-mer, a one or two base mismatch is a dramatic difference and can affect hybridization. So … with our labeling products … we're aiming to minimize the effect that we might see from hydridization, no matter what microRNA library or chip we're using."

To that end, the company is working on a technology that involves placing a fluorescent tag onto the end of a microRNA, rather than a nucleotide that is inserted into the small RNA.

"The only difference [between the two technologies is that] the labeling with our current Label-It [involves] attachments inside the sequence, so inside the 21-mer you'll have a nucleotide that will be labeled, [while the new] technology is aimed for putting [a label directly] on the terminal nucleotide," Hagstrom said.

"Our belief is that the Label-It technology is exceptionally good, so [by developing the new technology] we're kind of covering two bases," he added. "Both are non-enzymatic, both [don't] add nucleotides at either end, but [one] specifically [puts a label] on the microRNA."

Hagstrom said that "the tests are ongoing right now to determine which [technology] is going to give us the best hybridization parameters." The one selected is expected to be introduced as a microRNA-specific labeling product, under the Label-It name brand, "in the next couple months," he added.

In addition to microRNA-specific labeling technology, Hagstrom said that Mirus is also working on a purification product, but he noted that this is far less developed than a microRNA chip that is being developed with an undisclosed partner. Hagstrom said that a chip, which would have all the known microRNAs printed on it, might be ready for market launch as soon as sometime this year.

In terms of how the chip would work, Hagstrom said that "you'd purify your microRNAs from your tissue of interest, you'd label them, and then hybridize them to that chip. You would then see … which microRNAs are being expressed" in a particular tissue sample. The chip, he added, would be of particular use in looking for which microRNAs are up- and down-regulated in diseased tissue.

Hagstrom noted that while the total number of known microRNAs is small enough that all of them can fit on a single chip, Mirus has not made a decision as to whether it will make a species-specific or multi-species chip.

While this kind of product seems to be a run-up to a full-fledged microRNA diagnostic, Hagstrom stressed that the field is still in its infancy. "The belief right now is that microRNAs are involved in a vast amount of gene expression control, [but] we're so early in the game," he said. "Our goal right now is provide tools for people to do research in this area."

— Doug Macron ([email protected])

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