While Mirus, of Madison, Wis., touts itself on its website as a non-viral gene transfer company, selling tools for nucleic acid (including siRNA) transfection and labeling, the privately held company is also quietly trying to get into the business of making RNAi-based therapeutics.
But unlike most of the other RNAi-as-drugs firms, which develop siRNAs against specific targets and then try to figure out how to administer them, Mirus aims at perfecting its delivery methods first and going from there.
“We’re focusing on … delivery systems using the vascular system … for particles containing siRNA, as well as siRNA-expressing DNA vectors” that are designed to cause a continuous knockdown effect, Mirus CSO Jim Hagstrom told RNAi News. “The tissues we’re focused on mainly for this is liver and muscle.”
In terms of hepatic delivery, he said that Mirus has already been able to deliver siRNA complexes that can enter hepatocytes, but is still trying to figure out how to get the siRNAs active in the cells. “The last step is getting [the siRNAs] out of the endosomal compartment.”
Should technology be successfully developed, he said, hepatitis C and other viral diseases would be obvious targets for it.
For muscular delivery, Mirus has developed a high-pressure hydrodynamic delivery method for naked siRNAs that has previously been used mainly in mice for target validation research. But Mirus expects that this method could be used to deliver a variety of therapeutic siRNAs into muscle tissue, such as ones that induce angiogenesis in order to revascularize distal limbs.
Mirus is also exploring whether siRNAs could be used to treat hyperlipidemia and smallpox, and has already secured grants from the NIH to conduct these investigations.
The abstract for the hyperlipidemia grant states that Mirus plans to use its “intravascular in vivo delivery methods to characterize the siRNA activity profile and explore the possibilities to use siRNA for the treatment of hyperlipidemias.
According to the abstract from the smallpox grant, the company “will use vaccinia virus [the virus in smallpox vaccine] as a highly relevant model for variola virus [the deadly form]. Several genes from different viral pathways (transcription, replication, virion formation, virulence) will be targeted in vitro.”
So while Mirus envisions itself as one day getting into the drug development game, Hagstrom noted that “we believe that we would need to partner with someone for the application into that. Taking [drugs] all the way into the clinic is not something that our company would do by itself.”
For instance, he said the grants will be used to develop Mirus’ technology to the point where the company has the preclinical data to “convince an interested partner that they should look at this technology.”
“We don’t [have] the rights to any gene,” he explained. “We own technologies for delivery. So our interest is in partnering with people that are focused on a specific application for, say, the liver, or for muscle.”
And Hagstrom doesn’t expect there to be any lack of takers on Mirus’ collaboration offer.
“There’s a lot of hype in this world,” but “the delivery problem is not solved,” he said. RNAi-based drug developers, “the Sirnas and the Alnylams, realize that they do not have … the ability to deliver to high percentages of the cells using the bloodstream,” he said. “They’re going to need to work with partners.”
Hagstrom said that discussions with potential partners are ongoing and that he expects Mirus to strike at least one such deal within the next few months.