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Reagent Shop Altogen Begins Looking to Apply Technologies to Therapeutic siRNA Delivery


By Doug Macron

Looking to extend the use of its research products into the therapeutics field, Altogen Biosystems has begun exploring whether its transfection technologies can be used to deliver siRNA-based drugs, RNAi News has learned.

When it comes to research, "each of our customers has their own focus for delivery, [whether it] be siRNAs, microRNAs, [or] antibodies, and we offer the tools," Andreas Kim, vice president of research and development at Altogen, said this week.

But recognizing the growing interest in the therapeutic applications of RNAi, the company has also started testing the waters of drug delivery, with a particular focus on siRNAs, he added. "We see quite an opportunity" there.

To take advantage of that opportunity, Altogen has launched a research effort to use its technologies to address the "number of variables" associated with drug delivery, most notably protection of a therapeutic payload and avoidance of toxicity and immune responses, he said.

More specifically, Altogen has been working on how to best design its delivery vehicles so that they are naturally delivered to target tissues and organs, Kim noted. In conjunction with undisclosed collaborators, the company is also investigating the use of targeting molecules such as aptamers and antibodies in order to deliver siRNAs to specific parts of the body.

Thus far, Altogen has primarily been working on delivery to tumors and the liver, Kim said. But the company is also investigating delivery to the brain using its reagents that are able to cross the blood-brain barrier.

He cautioned, however, that "there are still studies that need to be done to make sure that [the delivery vehicle] is non-toxic [and] that it actually can cross the blood-brain barrier not only by itself, but when it is conjugated to a drug."

Even though Altogen's drug-delivery program is early stage, Kim said that the company already has generated a limited amount of siRNA data that it has been showing to potential pharmaceutical partners. At the same time, the company is also experimenting with delivery of other small RNAs, "mostly because of the way the market is right now," he added.

Indeed, many of the big biopharmaceutical players who have embraced RNAi as a therapeutic modality have also maintained an interest in other RNA medicines.

Merck, which made one of the biggest investments in RNAi through its $1.1 billion acquisition of Sirna Therapeutics in early 2007 (see RNAi News, 1/4/2007), has long made public that its interest is not limited to the gene-silencing technology, but a variety of RNA-based drugs. Similarly, Roche houses much of its therapeutic RNAi activities within its Kulmbach, Germany-based Center of Excellence for RNA Therapeutics.

Still, Kim stressed that Altogen's drug-delivery efforts are being conducted within "a very small program," and that the company's main interest, at least for now, remains in "offering [its technologies] as tools for customers."

About two years ago, the firm opened Altogen Services, a subsidiary that provides standard and custom research services. The former includes the generation of shRNA-expressing stable cell lines, genome-wide siRNA library screening, in vitro functional testing of siRNAs, and siRNA, miRNA, and shRNA design and synthesis.

Custom services are based on a client's needs for a particular research application, Kim said.

Meanwhile, Altogen continues to add to its stable of transfection products. Last month, it launched a pegylated liposome-based delivery reagent, primarily for use with siRNAs, as part of its In Vivo Transfection line.

When it comes to siRNA delivery, usually "there is a trade off," Kim said. "Either you have very efficient delivery, but then immune-response stimulation, or you [avoid an immune response but] … don't have very efficient delivery."

The PEG-liposome agent is "almost non-detectable by the immune [system and] … delivers very efficiently certain types of molecules," he said, noting that the reagent has been validated for siRNA delivery both intratumorally and systemically.

"The application of this reagent really is in non-immunocompromised animals," he said. With animal models lacking an immune system, interferon responses aren't an issue. "However, when you do have an animal with an active immune system, this can be a novel and effective product to use."

Altogen also offers lipid-based, polymer-based, and nanoparticle-based transfection reagents, all of which are validated for intravenous and intratumoral siRNA delivery. The lipid-based reagent is also validated for intraperitoneal administration.

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