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GE Healthcare Adds to HCS Toolbox with Adenoviral Vectors, Genotoxicity Algorithm

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WASHINGTON, DC — GE Healthcare took advantage of a busy week here as it launched two new products that are part of its recently disclosed "roadmap" for developing new HCS technologies (see CBA News, 10/10/2005).

First, at the Society of Neuroscience conference held here early last week, GE introduced a panel of validated adenoviral vector gene-delivery reagents, called Ad-A-Gene, which allow researchers to rapidly develop transient high-content cell signaling assays in cell lines of their choice.

Later in the week, at IBC's inaugural High-Content Analysis conference, also held here, GE launched a micronucleus formation software application module for its IN Cell Analyzer 1000 and 3000 platforms. The new module is expected to allow researchers to screen for genotoxicity early in the drug-development process.

The product releases add to GE's growing trove of tools to surround the IN Cell high-content screening instrument platform that the company took over when it acquired Amersham Biosciences in late 2003, and serve to solidify the firm as one of the few that can offer a comprehensive slate of high-content screening tools, including assay development tools, reagents, imaging markers, instruments, and image-analysis software.

In particular the adenoviral vectors make good on the company's recent promise to roll out new technologies for high-content screening in the coming year. In October, John Anson, head of product development in GE Healthcare's lead discovery unit, told participants at a cellular-analysis symposium press event that the company would conduct a tiered launch of a panel of 100 adenoviral-based gene elements (see CBA News, 10/10/2005).

Last week, the company introduced the first eight of those adenoviral vectors, with the remaining vectors to be launched periodically over the next few months.

"We have just launched a brochure identifying what the first 50 are going to be," Anne Jones, director of marketing for cellular sciences lead discovery in GE Healthcare's Discovery Systems division, told CBA News. "Eight are out now, and we're coming out with about 20 next month, and another 20 the following month."

GE also revealed how it would package the assays for sale.

"Based on customer feedback, and based on the most commonly used and required pathways that one wants to analyze, we've developed a panel of assays that are ready to go immediately for customers," Jones said. "In the first instance we are launching a panel of 50 assays, which covers roughly the top 16 cell-signaling pathways the customer may want to profile.

"If there is one which is not on the list, there are two things to note," Jones added. "First off, we have further plans to expand the range during 2006, and that will be based, again, on additional customer feedback and their knowledge of the market. But if there is a custom product required, we will work with customers and we may produce that product depending on whether we can agree to do that with a customer."

The vectors are based on technology developed several years ago by Frank Graham, co-director of the Center for Gene Therapeutics at McMaster University in Canada. According to GE, Graham formed a company to outlicense the technology. Canadian biotech Microbix first licensed the technology, and GE Healthcare now has access to the same license.

Microbix uses the technology, called AdMax, in its own vaccine development programs, and also offers services to parties that want scaled-up adenovirus production. In August 2004, GE Healthcare became one of Microbix's biggest customers in this area when it tapped Microbix to mass-produce the initial stages of the adenovirus vectors it released last week (see CBA News, 8/3/2004).

"We are happy to see our work on adenoviruses and gene transfer facilitating the development of an array of highly efficient vectors for gene delivery," McMaster said in a statement. "Among the main advantages of adenoviral vectors, the Ad-A-Gene Vector DNA does not integrate into the host cell genome, therefore, the expression and functional activity of the sensor is not affected by an integration event," he added.

The Ad-A-Gene vectors contain the gene encoding a protein target fused to either emerald green fluorescent protein or a gene encoding a response element that controls expression of a nitroreductase reporter gene.

"The GFP reporters that we have are primarily measuring movements of proteins within a cell, so you're trying to figure out, for example, whether a protein is moving from the cytoplasm to the nucleus," GE's Jones said. "The GFP fusions mostly measure translocations within the cell.

"The nitroreductase fusions are reporter gene assays, so they're measuring the switching on or off of proteins — so, whether a protein is about to be synthesized or not," Jones added. "So they're always active in the nucleus measuring transcription and translation of a protein. They're telling you slightly different things about a particular pathway."

New Algorithms

Also in October at GE's cellular analysis symposium, Anson identified an example of a popular high-content screening assay — genotoxicity testing — whose speed might be improved through the development of new image analysis algorithms on the IN Cell Analyzer.

"This is typically a very laborious process," Anson said at the time, adding that Cellomics had an automated application for the assay, but that it still took hours to do.

"The question is 'Can we run it in minutes rather than hours? Can we bring it further upstream in the drug-discovery process?' We're working on that right now," Anson said.

It turns out that there wasn't much more work to be done, as GE launched the application last week. Jones told CBA News that it is available for the higher-throughput IN Cell 3000 instrument.

Users of the genotxicity module on an IN Cell 3000 should be able to do acquisition and analysis in less than 10 minutes on a 96-well plate, Jones said. "If you were to do the same thing manually, it would take hours," she said.

Even the IN Cell 1000 plate reader — which is generally lower throughput than the IN Cell 3000 — can run the genotoxicity module, Jones added, but the time frame would no longer be on the order of minutes.

The genotoxicity module is another example of industry's attempt to bring toxicity screening to the early stages of drug discovery in order to weed out drug candidates and "fail faster."

In the later stages of the drug discovery process, Jones explained, a micronuclei test for genotoxicity is mandated by the FDA. GE hopes that users of the new module will be able to conduct this testing quickly on the IN Cell far earlier in the process. Even though a candidate that passes an early test must still be assayed for genotoxicity again later, at least a drug developer won't carry a toxic compound through the rest of the expensive and resource-consuming discovery pipeline.

Jones said that GE is aware of genotoxicity modules on Cellomics' ArrayScan and CompuCyte's iCyte.

— Ben Butkus ([email protected])

 

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