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Amaxa Pens Deal to Co-Promote New Nucleofector Delivery Tech with Dharmacon s siRNA Reagents

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Fisher Biosciences' Dharmacon unit and German biotech Amaxa this week announced a co-promotion agreement that will pair Dharmacon's siRNA reagent portfolio with Amaxa's newly launched Nucleofector 96-well nucleic acid cellular delivery technology.

For Amaxa, the partnership with Dharmacon — which is backed by the considerable marketing muscle of parent Fisher — could help it penetrate a market still dominated by Invitrogen's Lipofectamine platform. Dharmacon could also help validate the Nucleofector technology and give it a leg up against competitors such as Cyntellect, Cellectricon, and Fujitsu Biosciences, which sell or are developing similar high-throughput physical transfection tools.

Dharmacon, meantime, thinks the alliance will help it sell its siRNA reagents to researchers using difficult-to-transfect cell lines such as primary cells, human stem cells, and certain immune cells.

According to officials from both companies, the deal falls short of an exclusive co-marketing agreement; instead, Amaxa "will recommend Dharmacon's siRNA, and Dharmacon will recommend [Amaxa's] Nucleofector technology for the transfection of primary cells and difficult-to-transfect cell lines," Oliver Mueller, executive assistant and public relations manager for Amaxa, told CBA News.


"It's an interesting technology, and they might be able to get into cell types that you just can't transfect, even with Lipofectamine."

"We won't distribute Dharmacon's siRNA," he added. "We can recommend that customers use their product, and … they [will] recommend that customers use ours."

Bill Marshall, vice president of technology and business development for Fisher Biosciences, added that the companies have done "some nice research projects together to demonstrate the applicability of the technologies working together, and also to generate protocols on certain cell types that are of high interest to the research community."

Those types of cells include primary human cells, especially immunocytes such as T-cells, B-cells, and natural killer cells, the companies said.

"For many cell lines, our transfection efficiencies are between 50 and 90 percent," Mueller said. "For primary cells it's similar; but there are very hard-to-transfect primary cells such as natural killer cells, for example, where we only have a transfection efficiency of around 16 percent." But, Mueller added, other transfection technologies can't transfect NK cells at all.

"For other primary cells — for example, endothelial cells — we've got transfection efficiencies of 90 percent," Mueller said. "The prototype for a human primary cell is a T-cell, and we have an efficiency of 66 percent for human T-cells. So it very much depends on the cell type."

Dharmacon's Marshall told CBA News that "broadly speaking, you can divide things into chemical and physical transfection methods." Dharmacon has specialized chemical reagents for delivering siRNAs, Marshall said, because "chemical means are probably the most amenable for large-scale screens.

"There are certain primary cell types that one is able to transfect with chemical means," he added. "There are certain cell lines, though — an example would be Jurkat cells — that are difficult because it's non-adherent and difficult to transfect with chemical methods." Jurkat cells are particularly important because they are T-cells and therefore of great interest in immunology studies, Marshall said.

Nucleofector's physical transfection method permeates cells using electroporation, and also uses proprietary reagents to help keep the cells alive and healthy through what is an otherwise traumatic experience. The method helps transport nucleic acids to the cell nucleus, which is particularly important for primary cells, according to Mueller.

"Primary cells usually don't divide or divide very slowly, and with other transfection technologies, the plasmids usually only reach the cytoplasm and only enter the nucleus after cell division," he said. "But with primary cells you have to insert the plasmid directly into the nucleus if you want to have transfection and fast expression of the protein."

Still, chemical delivery methods such as Invitrogen's Lipofectamine appear to remain the "gold standard" for transfection — even for high-throughput siRNA screens. Sumit Chanda, a group leader at the Genomics Institute of the Novartis Research Foundation, uses Lipofectamine and characterized it as a "one-size-fits-all" transfection reagent that is especially effective for the types of large-scale siRNA and cDNA screens being conducted by his research group.

Lipofectamine is particularly amenable to high-throughput screens because the transfection process can still be completely automated. By comparison, a 96-well technology, combined with libraries consisting of a few hundred plates, "is still a lot of work," Chanda said.

"It's an interesting technology, though, and they might be able to get into cell types that you just can't transfect, even with Lipofectamine," he said, adding that "we can't even touch" Jurkat cells with reagents.

Baby Steps

Even if Amaxa's Nucleofector technology is unable to topple lipofectamine as the industry standard, Dharmacon's promotion of the technology may help differentiate it from other upstart physical high-throughput transfection methods, such as Cyntellect's LEAP platform, Cellectricon's CellAxess, and Fujitsu Biosciences' CellInjector.

Cyntellect, in collaboration with the University of Texas Medical Branch in Galveston, recently won a one-year, $338,000 grant from the National Institute of General Medical Sciences to apply LEAP to combinatorial siRNA library screens (see CBA News, 3/24/2006).

In April, Cellectricon said it had landed a first customer, a researcher at Sweden's Karolinska Institutet, for its recently launched CellAxess single-cell electroporation device (see CBA News, 4/21/2006).

And Fujitsu, which last month introduced a new version of its CellInjector that it said could transfect "problem" cells with double the efficiency of other methods, has had an ongoing collaboration with its first customer, the Whitehead Institute for Biomedical Research (see CBA News, 5/5/2006 and 12/19/2005).

Each of these vendors claims that its technology is ideal for transfecting traditionally difficult-to-transfect cells such as primary cells and stem cells, and each has already introduced or is currently developing a relatively high-throughput version of its platform.

Amaxa's original Nucleofector technology was launched in 2001 and has established a strong foothold in the basic research market. However, the technology had a very low throughput. To penetrate the drug-discovery and large-scale siRNA screening markets, the company developed the 96-well version of Nucleofector, and it now hopes that its alliance with Dharmacon can help validate it.

"The original Nucleofector was for one single cuvette, where you can do only a single transfection at a time," Mueller said. "Within one hour, you could do several cuvettes in a row — maybe 20 in total. But with the 96-well system, you can do one plate, which means 96 transfections, within a few minutes.

"This is, of course, very useful if you want to transfect siRNA libraries like the ones from Dharmacon in a high-throughput fashion," he added.

Marshall said that the introduction of the 96-well version of Nucleofector is one of the major reasons it chose to promote the Amaxa technology. "Now you can do electroporation at a reasonable price point — and the consumables that are used in it are certainly reasonable from a per-well cost basis."

Mueller said that the 96-well version of Nucleofector is currently available for order, and will likely be ready for shipping within a few weeks, so "obviously it's good timing for Dharmacon to help us promote it."

— Ben Butkus ([email protected])

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