Bioo Scientific's T3 Conjugation Kit can be used to target RNAs to specific cells in the body. Credit: BIOO SCIENTIFIC

It's not only clinical researchers who are looking for the best ways to get synthetic oligonucleotides into cells in living mammals. If the delivery problem were solved, says Phillip Sharp, who studies RNA interference (RNAi) at the Massachusetts Institute of Technology (MIT) in Cambridge, the ability to use animals to study physiology and disease would expand dramatically. “You can't make a knockout dog, but you could probe genetic function with RNAi.” He is optimistic that in a few years researchers will have worked out ways to exploit RNAi in the immune system and the digestive system, at least. It's an open question whether all tissues will be accessible, he says. “Formulating nanoparticles for certain tissue types is still a pretty sophisticated business.”

The challenge of delivering the molecules has not stopped companies from producing in vivo research tools. Those offering products for animal RNAi studies include Ambion, part of Applied Biosystems in Austin, Texas; Exiqon in Vedbaek, Denmark; Integrated DNA Technologies, headquartered in Coralville, Iowa; and Thermo Fisher Scientific, headquartered in Waltham, Massachusetts. These products are widely used in mice, but they lack some of the tissue or organ specificity that researchers desire. Companies are listening: in December last year, in what it announced as the first targeted delivery vehicle to hit the market, Bioo Scientific in Austin launched a kit containing a proprietary linking modality that allows researchers to conjugate RNA molecules of their choice to antibodies, in this way targeting them to specific cells.

This is still a young field, however, and scientists may rightfully feel that the PubMed database is a better source of such technology than product catalogues. In fact, many of the best encapsulation tools are not readily available, given that the tools companies are now seeding therapeutics companies with technologies and expertise, says Mark Behlke, one of the founders of Dicerna Pharmaceuticals in Watertown, Massachusetts. Dicerna is pursuing RNA drugs built on the same platform as some of the research tools offered by Integrated DNA Technologies, of which he is chief scientific officer. Matt Winkler says that he decided to sell Ambion, the research tools company he founded, and launch a therapeutics-focused company after a chance discovery with enormous therapeutic potential. Ambion scientists who were characterizing small RNAs for the company catalogue realized that cancer tissues were surprisingly deficient in certain RNA molecules.

There are other examples. William Marshall co-founded tools company Dharmacon (now owned by Thermo Fisher Scientific) before co-launching miRagen Therapeutics in Boulder, Colorado. Exiqon and Santaris Pharma, headquartered in Hoersholm, Denmark, are commercializing the tool and therapeutic aspects of similar nucleic-acid technologies. And scientists who a few years ago were developing tools are at other companies thinking about the best approaches for clinical trials.

M.B.