At A Glance
Name: Jiwu Wang
Background: Assistant Project Scientist, University of California, San Diego — 1999 Postdoc, UC, San Diego — 1996-1998 PhD, molecular biology, University of Southern California — 1994 BS, molecular biology, Peking University — 1989
Allele Biotechnology and Pharmaceuticals is a small, closely held firm located in San Diego. Founded in 1999 by president and CEO Jiwu Wang, the company has achieved profitability, secured nearly $1 million in government grants since 2001, and developed a revenue stream through its molecular biology services and oligo-manufacturing operations.
RNAi News recently spoke with Wang to discuss the company and where it is headed.
How did you get started in RNA interference?
My graduate work and postdoc work were all on RNA, in some aspect, mostly splicing. So, I’ve been paying attention to all RNA-related work for quite a long time. In ‘98, when I first saw Andrew Fire’s paper about RNAi in C. elegans, I immediately thought that it was something really interesting that I could use in my research. Actually, I started doing some RNA transfection as … an experiment, but not really related to later work at Allele.
Our main focus at Allele about RNAi is mostly because we’re really interested in promoters and terminators for our other NIH-funded projects.
So when I saw Tom Tuschl and colleagues’ work about using short double-stranded RNA for mammalian use, then I thought that our knowledge about expressing short RNA in mammalian cells could be used for this.
That’s pretty much what our first product is about. An [RNA] polymerase III … promoter and terminator to express short RNAs in mammalian cells for RNAi purposes.
Allele has three business focuses. Could you give an overview of these?
Sure. We started with some local services; we actually [do] oligo synthesis, and that is another reason we could jump into RNAi really quickly, because we have the facility and infrastructure to make RNA oligos or DNA oligos to support our internal research. [Synthesis services] also generate a lot of cash. That’s the first of our work.
The second aspect is pretty much like a research lab in a university setting: we get [a number of] grants from NIH, we do a lot of basic mechanism studies, and then, at some point — different from a school lab — we try to rev that up into some marketable product.
The third part is basically a service type of business where we provide our expertise in molecular biology and cell biology to other companies, or sometimes even to schools … a contract type of business.
Specifically, what kinds of services are you providing?
We have done gene cloning, gene constructing, protein-expression purification, especially at the beginning. That line of business is pretty much stopped right now because we focus more of our attention to our own technology development.
How much does RNAi play overall in Allele’s business?
It’s the main focus. It’s the number one focus. After we filed patent [applications] on the promoter and expression system, we’ve been moving into three new directions that are all related to RNAi.
The first is a completely novel transfection system. ... That is the subject of an NIH grant; actually, right now I’m spending most of my time preparing to apply for phase II of the NIH grant for this. We’re also finalizing a marketing plan for this.
The second line is related to the transfection [system] but in a cell array format. Actually, our patent application has just been published by the USPTO in a very addressable cell array respect.
The third is we’re looking into new vehicles for delivering RNAi reagents. Hopefully, that will have a lot more relevance to in vivo use than our previous methods. We haven’t been really working on animal models or anything like that, but that would be a new target area that we’d move into hopefully in the next three months to half a year.
What sort of approaches are you taking to develop new transfection technologies?
The current method that is near mature and that we’re trying to get a marketing plan on, is … complex-based, but it’s a totally new complex. … [Another] new vehicle that we’re looking into is based on a virus that has not been used for this before.
I can’t say.
What about the cell microarrays for RNAi?
That is at the early stage. There are actually two new papers just published using similar technologies. Some were related to David Sabatini’s cell-array method. That was for cDNA expression in a cell-array format.
We’re doing [things] differently than that. We’re trying to make the DNAs or RNAs for RNAi not spotted on the chip in the gelatin or anything like that. We’re making it really addressable, hopefully, with high density. But that’s at a very early stage.
In terms of Allele’s marketing plan, is the idea to develop the technologies then partner them out?
Our first product [the Line Silence linear expression cassettes] was partnered out to Promega. I think, right now, we are thinking of keeping [our transfection product] for awhile, because the transfection agent as a complex is a rather simple product. And, the usage of the product is rather well-known in the field. So, we are actually planning on selling that ourselves.
The next round of production is really a lot more in the infant stage, so we don’t really have a plan for that yet.
But our overall plan for all our technologies is partnering out, at some point.
Is any sort of RNAi-based drug development in the picture for Allele?
Yeah, but not by ourselves. There are two companies that are in collaboration with us. One is basically trying to get us to work on gene expression and gene expression networks. We’ve pretty much finished preliminary studies, and we’re very close to contract signing. Hopefully, we can coordinate some sort of news release a bit later.
The second contact we have with another company is actually using our vectors for in vivo use for drugs. They’ve been comparing our [non-viral] vector with other people’s, and so far it appears to be pretty good and hopefully they will eventually take ours.
Can you disclose what companies you’re talking to?
I’d prefer that I coordinate with those companies when they’re ready to talk about it.
Allele has a few patent applications filed. What do they cover?
Altogether we have three at the USPTO and one as PCT. … [They cover] basically two topics: RNAi templates and transfection.
What are your goals for Allele? Where do you hope to see the company in, say, three years?
Down the road, I would hope we could expand from the current size to maybe triple or quadruple. But our focus will always be on technology development. I think that’s what we’re good at.
We might, at some point, spin out the services division to other companies, to other local companies that we have been doing business with. We will focus all our attention on technology development.
We have professional consultants and lawyers, and they’ve been suggesting that we move more into clinical-related studies. But from my own point of view, I think our strengths are really the basic mechanism and basic technology. So, we’re probably not going to move anything very deeply into animal models or really clinical-related [areas.] We’re going to let other people, who are really good at it, do that.
How many employees does Allele have right now?
We have about 10, at this point.
And the company is profitable?
It is. It’s been profitable from the very beginning because of some service branches that we have established. And also, we have been very well funded by NIH. Last year, [our revenues] were about $700,000.
Is there anything else you’d like to add?
The company is also working on several projects that are not really related to RNAi. They are mostly related to RNA, including RNA signal amplification and in vitro antibody selection. I actually just got a phone call last night from a German company interested in our antibody selection.
So, we’re not just an RNAi company, even though we’re really small.