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Intradigm s Woodle on the Company s Foray into RNAi

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At A Glance

Name: Martin Woodle

Age: 49

CSO of Intradigm

Background: Genetic Therapy,
director of synthetic gene vectors –
1997-2001

Genta, director of drug delivery and
formulations – 1995-1997

Liposome Technology – 1987-1995

 

Intradigm was established in 2001 by Novartis to acquire and develop the gene delivery technology of its Genetic Therapy unit. Since that time, the company has begun exploring the ways in which it could use this technology to discover and validate gene function, as well as how it could be used to deliver RNAi-based drugs. RNAi News spoke recently with Intradigm CSO and co-founder Martin Woodle to talk about the company’s history and current endeavors.

How did you get involved in RNAi and come to found Intradigm?

While at Liposome Technology, I … became interested in nucleic acids as drug substances and went to Genta to work on their antisense substances. Novartis then recruited me into [a program using] gene therapy as the drug delivery system. Later, we worked with Novartis to form Intradigm to [make] use of gene delivery as a research tool in the gene function arena.

[At Intradigm], we wanted to devise methods to use gene delivery in animals as a modality for gathering gene and protein function information. One of the key aspects of that kind of situation is needing the ability to increase the expression of a gene, but also wanting and needing systems to decrease the expression of a gene. So we … used plasmids for … increasing gene expression, and began looking around for technologies to decrease gene expression. We approached a lot of the antisense companies and groups with ribozyme and DNAzyme technologies, but didn’t find those fields very receptive to making their technology available to a start-up. We began to see the literature about RNAi and decided to … try this newer stuff.

What do you see as Intradigm’s biggest challenge with its RNAi programs?

Our view is that [RNAi] is clearly a very successful technology…That doesn’t mean that you’re ready for a drug. You’ve still got to go from [having] something that seems like it will clearly solve a problem for the patient if we can find a good way to intervene. Now the challenge becomes finding that good drug modality...

With the RNAi species, it’s still very early days in terms of trying to address many of the issues. Fortunately the antisense and ribozyme work that’s preceded has helped reveal many of the issues that need to be addressed. But of course, new issues will emerge that aren’t fully anticipated.

Delivery is on everyone’s lips as a major issue for RNAi. How is Intradigm looking to handle that problem?

What we started with was delivery technology. Some of that is not at all applicable to clinical scenerios, yet is very effective in animals and can be used as a tool in gene function studies. Some of it we think does have a tremendous opportunity to create clinically viable systems.


Can you describe the technology you have that looks good for therapeutics?

We have a couple of technologies. One of them is very attractive in a local compartment. It’s based on complexation reagents that bind up the nucleic acid and can be injected into a tissue. The reagent provides a stabilization, it provides a cell binding and uptake, and then an intracellular release into the cytoplasm...

We also have what is probably … applicable to a large array of clinical uses, a technology we call TargeTran. It provides an ability to target to sites of pathology from an intravenous administration or [from] other parenteral routes of administration. It forms particles that have a layered structure. They self-assemble with a coding tha ... stops non-specific interactions ... [and] has exposed ligands that bind specifically to a target cell or protein.

The company just announced the development of siRNAs that achieve 90 percent inhibition of the SARS virus in vitro. What’s the next step with this program?

The next step is to get the delivery in animals. To show the ability to inhibit the virus where its invading and replicating within an animal model.

When do you expect to have these preclinical experiments underway?

Soon, [but] it’s always difficult to speculate.

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