Mr. Nash: Genetronics was founded in 1983 to exploit a technology that had been developed at the Max Plank Institute in Munich in the early 1970s. The technique involves fluidizing cell walls in such a way that molecules can have access to the interior of these cells to, for example, prompt the cells to fuse for the manufacturing of monoclonal antibodies. This technology was sort of a laboratory technique and the company was originally conceived to design, develop, standardize manufacture and distribute hardware that would make it possible for all labs to do this technique. The first product was launched in 1985 and now in molecular biology labs it is a ubiquitous technique throughout the world. Around 1992 the company began to receive more and more requests from customers to find ways to take this technology from the test tube lab bench and start to use it on rodents to help researchers to go from the test tube to mice and rats. Around 1993, we found a way to do that. I joined in February 1994 to write a business plan to expand the business because it appeared to us that if we can take the technology to rodents we could take it to large animals like me. There are a number of medical conditions where it is important that the active agent, the molecule of interest, not simply sit on top of the cell but actually gain access to the DNA and the nucleus itself. Our mission in life is to facilitate the intracellular delivery of molecules of one sort or another for the treatment of acquired or genetic disease.
TWST: What is the technique in layman's terms?
Mr. Nash: One of the reasons I joined the company is because the
technique is elegantly simple. The outer membrane of all cells, whether
they be insect cells or mammalian cells or tumor cells, consists of
quite complex layers of lipids. Molecules find it difficult to work
their way through these layers to get to the inside of the cell. Under
properly configured conditions of electric field it is possible to
reorganize that outer membrane temporarily, probably for under a minute,
but during that minute what happens is a transient permeability, a
temporary reorganization of this complex series of lipid layers. The
reorganization or the permeablization is manifested by the appearance of
probably thousands per cell of aqueous channels, or water columns. So
now instead of the molecule having to work its way through a dense and
complex mosaic of lipids it simply goes straight down what might be
thought of as a chimney of water. This facilitates the entry of the
molecule to the interior of the cell. As soon as the electric field
stops the cell begins to reform itself and in a minute or so the cell
wall is just like it was in the beginning but now the molecule is on the
inside of the cell not the outside.
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