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Following Yeast Array Launch, Invitrogen Puts Out First High-Density Human Protein Microarray

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Four months after launching its high-density yeast proteome array, Invitrogen has hit the market with the first high-density human protein microarray for identifying protein-protein interactions.

The ProtoArray Human Protein Microarray contains more than 1,800 human proteins from the kinase, membrane-associated, cell-signaling and metabolic protein classes. The chip was designed specifically with the drug discovery researcher in mind, Invitrogen officials said.

Yet even as Invitrogen wants “to make sure the product can make a big impact on drug discovery in the pharmaceutical area … we want to make sure that it’s accessible and used in the academic area as well,” said Charles Piazza, vice president and general manager of protein microarrays at the company. “We think there are a number of potential applications for protein arrays that have not been well-described, [and] we think this is really going to be the kind of platform technology that spurs innovation and creativity in the scientific community.”

According to Ben Hwang, senior director of global commercial operations in the Invitrogen Branford (Conn.)/ Protein Array Center, the human ProtoArray is the first chip that contains full length, sequence-verified probes. The exception to this is the kinases, which include the active domain only, Hwang explained. But, he noted, the firm knows the rest of the proteins are full-length because “they are QC’ed on Westerns for full-length expression and purity.”

The new chip utilizes Invitrogen’s ProtoP5 expression and purification technology, and according to Hwang, about 90 percent of the proteins on the chip should retain their conformation and biological activity. The proteins are derived almost entirely from the firm’s Ultimate ORF Clone Collection, and includes labeling and detection technologies from its Molecular Probes group and array development capabilities from ProtoMetrix, which Invitrogen acquired in April (see ProteoMonitor 4/9/2004). The company also used bioinformatics technology picked up with the acquisition of Informax, Piazza noted.

The Carlsbad, Calif.-based firm said the human ProtoArray enables identification of protein-protein interactions in as little as four hours, compared to weeks, which is the standard for experiments using non-chip techniques. This assertion was backed up by Anthony Koleske of the molecular biophysics and biochemistry department at Yale University, who beta tested the human ProtoArray.

“Traditionally, people who are looking for human protein-protein interaction have been using phage display or two-hybrid screens,” Koleske said, “There’s a lot of work-up that has to be done in those [experiments]. Here you just do the assay, and the next day you know what the protein is that interacts. It takes you one day instead of weeks to months. It’s a very powerful technique.”

Invitrogen launched its Yeast ProtoArray in July (see ProteoMonitor 6/11/2004). Prior to the launch, Barry Schweitzer, senior director of technology for Invitrogen, told ProteoMonitor, that the firm was likely to launch a human kinase array consisting of up to 400 proteins.

However, in the months following the release of the yeast array, the company was beta testing chips with multiple protein classes and up to 2,500 proteins on them. Invitrogen eventually settled on 1,857 proteins, according to Piazza. “We were looking for proteins that are of biochemical, biological high interest,” he said. “We were also looking to make sure that we can get high-quality, full-length proteins expressed. There were some that don’t express as well on our system that didn’t make the cut. But we’re working on building that content.”

Piazza added, “We’ve enriched for kinases because of the general interest in that area, and just under 200 of the proteins on the array are kinases. Considering that the current estimate is that there are probably 500 or so kinases in the human proteome, that gives us fairly high representation in that segment.”

There was no official pre-launch of the product, Hwang said, but the firm already had orders for the human ProtoArray before last week’s official introduction. During the time the sales team was rolling out the yeast array, Invitrogen was working with beta testers on the content of the human chip. “In earnest, the sales team started talking about the human array and had a launch date settled in probably middle of October,” said Hwang.

The chip costs roughly $1,200 — significantly higher than the average price of whole-human-genome chips that are sold for gene-expression applications at a cost of $500-$750 — but most of the fluorescent scanners, including those sold by Axon, Tecan, and Perkin-Elmer, can read the chip, according to Piazza. He noted, however, that the Affymetrix scanner, which is specifically designed for Affy chips, and scanners that illuminate from the bottom won’t work with the ProtoArray.

“It has to illuminate from the top, and clearly where the chip is placed, [it] needs to be able to hold a regular-sized microscope slide,” said Hwang. “From that perspective, the utility is quite high.”

He added, “In terms of applications requiring radioactivity, most phosphoimagers would work. For the folks without phosphoimagers, we’ve had success just exposing it on X-ray film, and then scanning the X-ray film. We designed the system to be an open system specifically to serve as wide a range of a segment as we can.”

As far as its pipeline goes, Invitrogen is trying to accelerate the build-up of proteins it can place on an individual chip, Piazza said. “We see that as our major thrust — and developing additional applications for the technology,” although he declined to say what those applications would be.

“We took a very deliberate approach in terms of coming to a decision that having a high-content chip going forward is the right strategy,” Hwang said. He referred to previous attempts in the industry to develop chips based solely on sub-classifications of proteins, such as kinases or nuclear proteins, as “flavor of the month.” He said Invitrogen views its own chips as “four, five, or six theme chips on one.”

“It allows you to do experiments that are focused on particular applications, but also enables you to screen across the entire proteome,”

— EW

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