Designer Virus Stalks HIV
Development Going Ahead Despite
Serious Potential Problems

By Kristen Philipkoski
Wired News
BERKELEY, California -- It took Adam Arkin and David Schaffer just $200,000 and a grad student to develop a potential treatment for AIDS. And that scares them.
That's because the therapy itself is a virus. The Lawrence Berkeley National Laboratory assistant professors created a virus altered to latch onto HIV and mute its ability to become AIDS. They've tested the theory in a computer model and in cells in a dish. The results have been promising, and if they continue in that vein, the researchers could begin animal testing by the end of this year.
Arkin said this week at the International Biotech Summit at the University of California at Berkeley that it was almost too easy for him and his colleagues (Schaffer and then-grad student Leor Weinberger) to build the anti-HIV virus.
"If I can do it, anyone can do it," Arkin said. "That's going to be a problem."
Well, maybe not anyone. After all, Arkin and Schaffer are not your run-of-the-mill lab jockeys.
Still, bad guys can be brilliant, too, which is even more reason for the good guys to understand new biotechnologies as thoroughly as possible.
"The genie is out of the bottle, so we might as well study these things in earnest," Arkin said in an interview.
Plus, the potential good could outweigh the bad. By using a computer model of what happens to the immune system when it's infected with HIV, Arkin and his colleagues have designed a potential AIDS treatment that would remain with the patient as long as he or she has HIV, meaning it would prevent AIDS from arising even in patients who otherwise would have developed the disease after a decade of latency. They also predict HIV would not become resistant to the virus.
The treatment is made of a gutted HIV virus. The harmful parts of the virus are removed, and in their place the researchers have inserted a DNA cargo that inhibits HIV's ability to kill immune cells. It latches onto the natural HIV and spreads along with it, even from person to person.
If this process sounds familiar, it's because it is essentially gene therapy, albeit a transmissible gene therapy. But the term "gene therapy" has fallen out of favor because of a handful of fatalities in clinical trials and, after nearly three decades of research, no gene therapy method has been proven to work consistently.
So Arkin and Schaffer are instead calling the process "synthetic biology." Despite appearances, it's not an arbitrary term: The researchers are synthesizing biological elements into machines to do their bidding.
"An artificial virus is one such product, since it is designed and constructed using molecular biology tools for a specific therapeutic application," Schaffer said. "As another example, Jay Keasling in our department engineers bacteria to produce small-molecule pharmaceutical drugs."
Lawrence Berkeley National Laboratory, MIT and other institutions have established departments and courses dedicated to this manipulation of human molecules.
"All the capabilities are found in nature, just not in the right order to do what we want to do," Arkin said. "It's like changing the computer language. (Cells) perform amazing engineering feats under the control of complex cellular networks. We didn't design it, evolution did."
Computer modeling is key to figuring out what bacteria or viruses might do in a given situation. The computer model Arkin and Schaffer used showed that their therapy won't likely eliminate all HIV cells in a patient. But if the treatment inhibits HIV too much, the good virus won't be able to propogate.
"Maximal inhibition actually causes the therapy to extinguish itself," Schaffer said in an e-mail.
Without the computer model to guide them, the researchers may not have detected such subtleties. However, other labs like Virxsys (researchers there published work that gave Arkin et al. a foundation for their own work) are further along in developing a similar therapy (although the Berkeley researchers' method is unique in its piggyback effect) without the benefit of a computer model. Scientists there are already testing their treatment for safety in humans, and hope to test for efficacy by the end of this year, said Boro Dropulic, the company's founder and chief scientific officer.
Arkin and Schaffer's computer model will also help them foresee potential problems, which are plentiful when trying to treat a deadly disease with a manufactured virus. This is a virus that can be spread by having sex, just like HIV (although if it works, that could be a good thing). It's also possible that HIV and the therapeutic virus could mutate around each other and recombine to make an altogether new virus.
"I can't say now it won't make it worse," Arkin said.
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