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Startup Intrexon Closes $1M VC Round to Develop Tools to Uncover Location of Sub-Cellular Events

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"Location, location, location" is a real estate adage, but it could also be the buzzwords of nascent biological reagent provider Intrexon, which this week said it closed a $1 million round of private equity financing to help develop and market its line of location-dependent sub-cellular genetic tools.

Intrexon's technology is based on the theory that knowing the location of sub-cellular events may determine a distinct phenotype, a notion that the company believes is growing among researchers. As the company's CEO puts it, "location matters."

The company does not yet offer products suitable for industrial-scale screening campaigns, but it hopes to forge collaborations with academic and government researchers in the coming months to validate its reagents and serve as a springboard to the pharmaceutical sector, Intrexon CEO Robert Beech told CBA News this week.

"We're really at the stage right now where these reagents are being used … to go in and characterize these sub-cellular location-dependent events, but we haven't yet put together a coordinated set of in vitro cell lines where you could do something like high-throughput screening and so forth," Beech said.

Intrexon has been around since 1998, but until late 2005 was known as Genomatix — not to be confused with the German bioinformatics company of the same name. Its switch to the Intrexon moniker (a combination of "intron" and "exon") supported a shift in strategy for the company from primarily a custom transgene provider to a reagent shop — though it still provides some custom services, Beech said.


"We see this as a next generation beyond siRNA."

The flagship technology around which Intrexon hopes to build its business is a set of DNA vectors that target selected kinases in various sub-cellular locations, such as the Golgi apparatus, nucleoli, and apical membrane, sold under the brand name mDECOY.

According to Beech, these mDECOY vectors produce a recombinant protein that comprises three main functional elements: A decoy inhibitor, which "tricks" a target kinase into binding it; a localization signal, which causes the inhibitor to localize to a precise subcellular location; and some type of a bioindicator, such as an epitope tag, that allows the researcher to verify the protein's sub-cellular location in fixed cells.

"The way I like to describe it is the nano-geography of the sub-cellular space is the new frontier," Beech said. "I think that researchers are starting to realize [that knowing] 'where' [something happens] in a cell can determine a distinct phenotype versus inhibiting that same interaction — typically a protein-protein interaction — in another location in that cell. So location matters."

Robert Murphy, director of the Center for Bioimage Informatics and professor of biological sciences and biomedical engineering at Carnegie Mellon University, buys into the importance of the location of subcellular events. Murphy's group is developing a set of techniques and analysis methods — dubbed "location proteomics" — which he hopes will eventually feed into a database detailing the location of every protein in a variety of cell types (see CBA News, 2/15/2005).

"Intrexon's technology is exciting in allowing analysis of position-specific kinase effects," Murphy wrote in an e-mail to CBA News. "As more and more specific targeting sequences are learned through location proteomics projects, even more organelles — and subdomains of organelles — can be targeted by this approach."

Beech and colleagues at Intrexon believe that a great deal of drug toxicity is likely caused by off-location effects. Therefore, the company's tools may prove useful as a way to better understand drug toxicity. Furthermore, Intrexon believes that mDECOY might be able to provide an alternative or add-on to RNAi as a cellular research tool.

"We see this as a next generation beyond siRNA," Beech said. "Because of the way it works, siRNA, if it's blocking its target before it can be translated into a protein, then it's preventing the protein from going to any of the locations to which it was destined. By that, it's going to affect its target in all the locations to which it was destined.

"As it's shown more and more that location matters, we believe that the siRNA market will start to incorporate the use of these tools to resolve where in the cells the target needs to be inhibited," he added. "So this pan-cellular versus sub-cellular inhibition is going to be a big part of the industry."

Intrexon currently has 26 mDECOY kits available — 13 pairs each targeting the same kinase and locations, but using different promoters. Beech anticipates the company will have 50 to 80 kits out by the end of the year — mostly for kinases — and will start branching into next-generation drug targets such as phosphatases soon thereafter.

In addition, the company will devote 2006 to cultivating early adopter collaborations with academic and government researchers. Beech said that Intrexon already has such collaborators, but declined to disclose their identities due to confidentiality agreements. Once the company jumps through the usual hoops of validating its technology through publications and presentations, it will begin to focus on expanding its market reach.

"That's an eventual part of the strategy, and certainly these are available to industry now," Beech said. "But my sense is that they are most appealing now to academic and government researchers who are more interested in characterizing basic biomolecular interactions, filling out bioinformatics systems, and creating reference models of sub-cellular phenotypic effects."

These reference models, Beech said, will eventually be able to serve as the basis for screening systems, "because one has to know why the readout would be relevant. So if a particular small molecule were put through the screening process, and it was shown to inhibit its target in multiple sub-cellular locations, one would want to be able to look over and see what this means, for predictive toxicology effects."

The private-equity financing was provided by NewVa Capital Partners, a regional investment partnership managed by Third Security. NewVa last made an investment in Intrexon in May 2005.

— Ben Butkus ([email protected])

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