蛋白质生物芯片公司转向生物标记

生物谷

生物谷报道：一个新的蛋白质组芯片技术宣布可以通过高通量的蛋白质相互作用在药品方面进行研究。

Invitrogen公司作为第一个获得人类蛋白质芯片商业化的公司在最近的海报宣传，至少到目前为止，放弃通过单一的芯片技术了解人类完全蛋白质组伟大的计划。相反生物公司跟大学实验室开始集中在解决明确的科学问题。尽管这项技术有着很大的通过药品发明创造巨大国家收入的潜力，很多公司希望通过第一个利用这项技术作为生物标记的研究工具。

Invitrogen该文发表在：Nature Biotechnology 23, 3 - 4 (2005) doi:10.1038/nbt0105-3

具体内容详见如下：

Protein chip companies turn to biomarkers Cormac Sheridan Dublin

A new proteomics chip claims to allow high throughput protein-interaction studies used in drug discovery.

Protein analysis is becoming increasingly easier with the latest generation of biochips but whole proteome studies still lie some way off.

Brookhaven Protein Data Bank/KRT

Invitrogen's recent launch of what it billed as the world's first commercially available human protein microarray may, paradoxically, signal the abandonment, for now at least, of the grand ambition of characterizing the entire human proteome using a single chip. Instead, biotech companies and university labs are focusing on solving specific scientific issues. Although the technology has long-term potential to yield revenue through drug discovery, many companies hope to cash in early on by first using the technology as a biomarker discovery tool.

Invitrogen, of Carlsbad, California, unveiled its new protein microarray, called ProtoArray, on November 18. Although several core proteomics facilities have already developed higher density arrays in-house, the product, with 1,800 immobilized human proteins, has the potential to open up proteomics research to a wider audience. The array contains a cross-section of gene families including proteins that are useful in drug discovery such as kinases, membrane-associated cell signalling and metabolic proteins. Although the ProtoArray contains a limited number of proteins at present, Invitrogen aims to produce successive microarrays "each of them containing substantially more proteins than the previous version" during 2005, says Paul Predki, a senior scientist at Invitrogen's protein microarray group.

The company claims that the product has the potential to extend researchers' abilities to perform high-throughput protein-interaction experiments in parallel and enable studies of interactions between human proteins and other biomolecules, such as RNA and DNA, to be conducted in a similar fashion.

But, according to Steven Bodovitz, of market research firm BioPerspectives (formerly BioInsights), in San Francisco, California, the company will have to convince skeptics that such large numbers of experiments can be done in parallel under the same set of conditions. "It looks great," he says, "but if you ask biochemists, they generally have their doubts that this kind of stuff works."

The earlier analogies between proteomic and genomic analysis have been either over-simplistic or completely misleading, as the level of complexity of the former is orders of magnitude higher.

Many protein biochip companies have been bedeviled by the difficult trade-offs required to produce a robust working platform. This requires juggling with multiple factors, including getting the surface chemistry right, inserting sufficient content in the form of proteins or capture agents, such as antibodies or other protein binding molecules, and using a detection method with sufficient sensitivity and range of operation to deliver useful data.

The early analogies between proteomics and genomic analysis have been either overly simplistic or completely misleading, as the level of complexity in the former is orders of magnitudes higher. "I think there is [now] a bit more realism about the expertise and the infrastructure required to do good proteomics studies," says Dolores Cahill, director of the Center for Human Proteomics at the Dublin-based Royal College of Surgeons in Ireland.

The remainder of the protein microarray sector is characterized by a widely heterogeneous set of companies and technologies. According to Bodovitz, a dozen firms are either developing or shipping interaction biochips (see Table 1). Around 50 more are focused on capture biochips, which are populated with antibodies, aptamers or other protein binders as opposed to the physiologically functional proteins that are loaded onto interaction microarrays. Capture chips, which are based on the classical enzyme-linked immunosorbent assay (ELISA) format, are used primarily for protein expression profiling and for limited protein-protein interaction studies. "Some technologies are the equivalent of Ferrari, some are the equivalent of Ford," says Cahill, who has developed a microarray research platform populated with 10,000 unique human proteins.

Table 1 Nature Biotechnology 23, 3 - 4 (2005) doi:10.1038/nbt0105-3

Protein chip companies turn to biomarkers
Cormac Sheridan

Table 1 Selected companies developing protein interaction biochips
Aclara Biosciences, Mountain View, California	Panomics, Redwood City, California
Biacore International, Uppsala, Sweden	Protagen, Dortmund, Germany
Invitrogen Corporation, Carlsbad, California	ProteinOne, College Park, Maryland
JPT Technologies, Berlin	Proteome Systems, Sydney, Australia
Meso Scale Discovery, Gaithersburg, Maryland	TeleChem International, Sunnyvale, California
NextGen Sciences, Huntingdon, UK	Serologicals, Atlanta, Georgia
Source: Protein Biochips: Parallelized Biology for High-Output Biology (BioPerspectives (http://www.BioPerspectives.com) & Bachmann Consulting (http://www.JBachmann-Consulting.com), 2004).

This next year, is going to be pivotal in the field of protein biochip

Rolf Mathies
Early bird, Hamburg, Germany

Several of the early contenders have either gone out of business or, like Zyomyx of Hayward, California, have been forced to rein in their ambitions. Those remaining in the field are now focusing on microarrays that address specific needs—and not proteome-wide studies as initially planned. "Instead of thinking about complete coverage, the key is to make do with existing content and organize it in such a way so that you can use what you have on the chip to answer a meaningful research question," says Bodovitz.

Invitrogen gained much of its protein microarray capability through its April 2004 acquisition of Protometrix, of Branford, Connecticut, a company formed to commercialize the research of Michael Snyder at Yale University, in nearby New Haven. On November 30, Invitrogen picked up more intellectual property, in an exclusive licensing deal with Zyomyx, which had abandoned its own attempts to build a platform. For now, Invitrogen is the biggest player on the block, says Aaron Geist, analyst at Robert W. Baird, of Milwaukee, Wisconsin, with a worldwide footprint, sales and marketing muscle, and $1 billion cash. Investors, he says, have yet to appreciate "how significant Invitrogen's efforts have been of late."

The commercial availability of the first human protein microarray is evidence of the growing maturity of this complex technology. But it may take some time before this is translated into bankable drug discoveries. By contrast, biomarker research, for both drug development and diagnostic applications, offers an early payoff for proteomics research, says Bill Rich, CEO of Ciphergen Biosystems, in Fremont, California.

His firm claims to be making progress in the area, having sold over 500 units of its protein expression profiling systems. Judah Folkman and Giannoula Klement, of Boston Children's Hospital, Massachusetts, used the device to show that platelets taken from mice with undetectable tumors appear selectively to sequester proteins involved in regulating angiogenesis. Their presentation at the annual meeting of the American Society for Hematology in San Diego on December 7 led to a short-lived 32% surge in Ciphergen's share price.

This next year, Rich says, will be a pivotal one in the field of protein biochips as many research facilities and organizations are coming out of a period of evaluation and will soon start to select the platforms, protocols and strategies that will guide their proteomics research. "The technologies that speed the translational medicine process are going to be the winners," he says.