By Malorye A. Branca
November 15, 2002 | What keeps some HIV-infected people from developing AIDS? The answer has eluded researchers for more than a decade.
But once they got their hands on some protein chips, one group of researchers very quickly put names to three proteins that may be long-sought “factors” that protect against AIDS. Their study, published in Science in late September, won international attention both for the researchers and for the chips they used, which are from Ciphergen Biosystems Inc.
Renowned AIDS researcher David Ho, scientific director and chief executive of New York’s Aaron Diamond AIDS Research Center, led the bid to unmask the “CD8 antiviral factor (CAF),” made by those immune cells. His team included scientists from the Diamond Center, Ciphergen, and Rockefeller University.
“Since 1986, we have known that CD8 T cells, when stimulated, could release a factor that is capable of suppressing HIV,” said Ho in a late September conference call. Jay Levy and his colleagues at the University of California at San Francisco were responsible for that finding, but they didn’t actually identify the molecule. Since then, several high-profile groups, including HIV’s co-discoverer, Robert Gallo, have tried to fill in that gap.
Last year, Ho’s team started using Ciphergen’s ProteinChip system to generate protein-expression profiles from some people without HIV, some infected with HIV who became ill, and some who have been infected for a long time without getting AIDS. “We came at the old questions with a new tool,” said Ho.
Three proteins, identified as alpha-defensins-1, -2, and -3, stood out in their research. “We feel confident that alpha-defensins are a major contributor to CAF activity,” said Ho. However, not everyone in the scientific community is as convinced yet. Levy himself has already been quoted as saying, “This is not [CAF].”
Still, Ciphergen is basking in the news, which comes on the tail of some high-profile cancer studies that also used the company’s chips. “Business is growing rapidly for us already,” says Matt Hogan, chief financial officer at Ciphergen, based in Fremont, Calif. “But publications like this definitely drive and accelerate your sales.”
Findings like this could help spur sales of proteomic technologies overall. “The study’s a validation that this approach will speed up such discoveries,” says Rob Cavallo, product manager for protein microarrays at PerkinElmer Life Sciences Inc. He says the market for protein chips is primed. “People are just beginning to recognize the value,” he says.
Ciphergen’s technology unites protein chips with mass spectrometry. The Ciphergen chips are covered with various binding factors -- molecules that can pull specific types of proteins out of a sample. Once proteins are captured, whether they are known or not, mass spectrometry can be used to determine their identity. Other types of protein chips use antibodies designed to capture known proteins. “With these other, antibody-based chips, you have to know something about the proteins you are looking for,” says Cavallo. Both types of systems let researchers compare the kind and amount of certain proteins they find in different samples.
One of the main barriers to adoption of this approach is that protein chips are much more difficult to make than DNA microarrays because proteins are structurally more complex and therefore harder to work with. “Pharma companies are waiting for commercially available, preprinted products rather than developing their own assays,” says Cavallo. Such products are just beginning to become available.
Hogan concedes that proteins are hard to handle, but he maintains that Ciphergen’s technology is now accessible to biologists at large thanks to product refinements and training the company offers.
Some customers end up collaborating with Ciphergen. “At first [the Diamond center] was just a client,” says Hogan. “They started to understand how the system could be used, and we built it into a collaboration.”
Wisely, Ho himself offered up some caveats regarding this new finding. “It is not entirely clear that we can take this discovery and turn it into a useful therapeutic,” he said. The defensins are rather large proteins, which makes them unwieldy as actual drugs. Researchers are now looking for the particular “active sites” on these molecules that help them fight HIV’s effects.