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Despite Restructuring Plans, Roche to Continue Development of High-Density Peptide Arrays

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Although Roche plans to discontinue a number of its NimbleGen microarray product lines at the beginning of next year, it is currently developing high-density peptide microarrays, and has made them available to scientists from Sweden's SciLifeLab, BioArray News has learned.

A company spokesperson this week said that even though Roche is likely to stop selling most of its DNA array portfolio on Jan. 1, it will "continue to work" on the peptide array technology and will provide early access to the chips to additional "selected collaborators." The spokesperson confirmed, however, that the high-density peptide arrays are not yet commercially available.

Roche earlier this year discussed plans to largely exit the microarray business and refocus NimbleGen's resources on the target enrichment market. As part of those plans, the firm plans to reduce headcount at Roche NimbleGen's headquarters in Madison, Wis., and close Roche NimbleGen's two main manufacturing sites in Reykjavik, Iceland, and Waldkraiburg, Germany (BAN 6/12/2012).

However, earlier this month Peter Nilsson, site director for the Human Protein Atlas and director of the affinity proteomics platform at SciLifeLab in Stockholm, told BioArray News that he has been using Roche-manufactured high-density peptide arrays, and had positive things to say about the nascent platform, calling it "something that can change the protein array field."

According to Nilsson, he and other collaborators at SciLifeLab have had access to peptide arrays that offer "whole-proteome coverage" of over 2 million peptides per slide. Each peptide on the array is constructed from 12 amino acids overlapping for each coding protein covered. To date, Nilsson has used the chips for epitope mapping of antibodies and said the experiments have produced "amazing data." Nilsson added that he had also used the peptide chips for autoimmunity profiling.

It is unclear how long Roche has offered high-density peptide arrays to collaborators. Mathias Uhlén, professor of biotechnology at KTH, the Swedish Royal Institute of Technology, and manager of SciLifeLab Stockholm, discussed the development of whole-proteome arrays based on synthetic peptides at a Human Antibody Initiative workshop in Geneva in 2010.

SciLifeLab is a two-year-old translational medicine and molecular bioscience collaboration between four universities in Stockholm and Uppsala. The Swedish government recently earmarked $100 million to fund the center's activities, including its DNA and protein array platforms, for the next four years (BAN 9/11/2012).

Roche's technology allows the manufacture of high-density oligonucleotide arrays, with some products, such as its comparative genomic hybridization arrays, available in a 4.2-million-marker format.

The company synthesizes its arrays using its maskless array synthesizer system, which employs a solid-state array of miniature aluminum mirrors to pattern 786,000 to 4.2 million individual pixels of light to build the biomolecules on its chips using photo-mediated synthesis chemistry.

Nilsson said that his lab has been using protein arrays with a similar density. Roche makes and distributes the peptide arrays, he said, which SciLifeLab runs using the same MS 200 Scanner that is optimized for use with NimbleGen DNA arrays. Though Nilsson characterized the technology as "very early phase" and said that, as far as he knew, "very few" collaborators have access to it, he believes it "really has potential" and is considering eventually making the peptide arrays available to other researchers in Sweden via SciLifeLab.

"Being a national resource, we are looking to [the] future of how to best provide services," said Nilsson. Roche NimbleGen's high-density peptide arrays would be the "perfect starting point" for biomarker discovery he said, followed by validation on SciLifeLab's protein arrays, which are printed internally using Arrayjet's Marathon microarrayer.

Nilsson's main activities within SciLifeLab include antibody-based profiling, run on Luminex suspension bead arrays, and antigen-based profiling, which relies on the antigens created within the Human Protein Atlas for the generation of the monospecific polyclonal antibodies. The antigens are then printed on microarrays using the Marathon and used to validate all antibodies produced.

A number of other companies do offer peptide arrays, albeit at lower densities. Berlin-based JPT, for instance, on its website advertises the ability to survey "thousands" of peptides using its PepStar arrays, while Heidelberg, Germany-based PepPerPrint says it can print up to 156,000 peptides on its PepPerChip peptide arrays.

An EU-funded project, called PepChipOmics, is also developing a 2.1-million-marker peptide array platform using light-directed synthesis, as well as an imager capable of detecting multiple real-time interactions on the arrays. SciLifeLab's Uhlén is taking part in PepChipOmics, which involves several other European universities, as well as French array imaging firm Genoptics.

According to Nilsson, should they become more widely available, such high-density peptide arrays could "potentially replace spotted protein arrays," at least for initial discovery work, though he noted that peptide configurations may enable different types of binding compared to the same sequence in protein context, so there still will be a "huge need for protein arrays as a verification step."

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