When Corning closed its microarray technologies business unit last fall, daunted by fierce competition and suffering from a sharp downturn in its core telecommunications business, it looked as if the company had left the microarray arena for good. But the closure of the microarray unit did not stop its science and technology division from quietly pushing along its microarray-related research. As a result of this research, Corning is now poised to reemerge on a different, less crowded shore of the biochip landscape: the virgin territory of membrane protein arrays.
In two articles published in the Journal of the American Chemical Society last month, researchers from the division’s biochemical technologies unit described their new approach for delivering functional membrane proteins onto surfaces, and a new technology for detecting SNPs on a microarray.
To generate their protein arrays, the scientists spotted membrane preparations derived from cell lines that each overexpress a specific G-protein coupled receptor (GPCR) onto glass or gold substrates coated with gamma-aminopropylsilane (GAPS). This surface differs from the GAPS-coated slides Corning currently markets to microarray researchers: “The trick of the trade is in the types of GAPS that we have,” said Joydeep Lahiri, the paper’s corresponding author and leader of the company’s high-sensitivity assays group, adding that Corning had applied for patent protection of the technology.
Not only were these arrays remarkably stable — at least for two months — but more importantly, the GPCRs were functional in binding assays with ligands and inhibitors. Moreover, the assays were able to distinguish between three subtypes of the adrenergic receptor, based on their affinities. In theory, any protein expressed in a membrane in significant amounts could be deposited in this way.
“On the one hand, it’s deceptively simple, and on the other hand, it clearly works very well,” said Jonathan Blackburn, chief scientific officer of Sense Proteomic, a microarray company based in Cambridge, UK, which also works on functional membrane proteins. But the Corning scientists’ article is mostly a proof of concept, he believes. “It demonstrates what’s possible, but there is a lot of work to be done to take this forward,” Blackburn said.
Membrane Proteins Hard To Get, But Key in Screening
With membrane proteins, and GPCRs in particular, being some of the important drug targets to date, the obvious application for the arrays would be in drug screening, especially against receptor subclasses and orphan receptors. Other potential uses, according to Lahiri, are studies of protein-protein interactions and assays that “go beyond just binding of ligands,” probably meaning signal transduction events.
One of the major limitations at the moment is the lack of membrane protein content — Corning, in its publication, only used commercially available membrane preparations. But the company has already been approached by several potential content providers, and is hoping to collaborate with several of them in the future. However, “we are not in a tremendous hurry to mass market GPCR chips,” said Donald Munroe, business development manager at Corning Life Sciences, adding that “we would like to identify potential partners, probably over the next few months.”
The next step in the commercialization process will be to validate the published data and expand the scope of the technology. “It certainly works for different kinds of membrane proteins, and it also works for different kinds of lipids,” said Lahiri, mentioning that they had included the EGF receptor in their studies since submitting their paper. Early-access partnerships with pharmaceutical companies, which would double as content providers, are likely to follow. “At this point we are far more interested in learning and establishing key relationships than we are in selling to every lab across North America,” said Munroe, but it is possible Corning will market the technology more widely later on.
SNPs Eclipsed By Array Competition
Corning’s chances might be better in the protein array field, where there is no dominant player at the moment, than in the SNP arena. Its SNP detection method, described in the second Journal of the American Chemical Society paper, relies on fluorescence resonance energy transfer (FRET), and combines aspects of molecular beacons and competitive hybridization. In this approach, unlike others, samples do not need to be labeled by the user.
Despite these potential advantages, Corning sees SNP arrays as an unattractive commercial proposition. “The SNP field, whether it be solution-based assays or microarray-based assays, is a crowded field, and a highly competitive field,” said Lahiri. He did not rule out the possibility of licensing this technology out to another organization, but said the company had decided not do develop it further, at least for now. However, Lahiri added, “if there is very significant interest, things might change.”
— JK