Diosynth taps Swiss tech for protein production
with a Swiss firm for a technology that could dramatically reduce
the time and cost of developing new cell lines for manufacturing
proteins, writes Phil Taylor.
The technology, developed by Plan-les-Ouates-based Selexis, allows stable cell lines for protein production to be created in less than half the time of existing techniques, and this answers the need for new systems to get proteins into production more quickly.
The earlier a drug gets into production, the earlier it can start clinical trials and potentially reach the market. Earlier this year, a report published by the Tufts Centre for the Study of Drug Development concluded that shortening development time was one of two primary means of improving the efficiency and productivity of R&D, along with terminating less promising projects earlier.
In mammalian biosynthesis, cells are modified with vectors carry the gene coding for the protein that is to be produced. A number of copies of the gene will incorporate into the chromosomes of the cell, and the cell's own machinery transcribes and makes the protein. But a number of these inserted sequences or transgenes will not function correctly as the host cell will in some cases 'silence' their activity.
Using Selexis' technology - called MARtech - the proportion of transgenes that remain active and available to make protein is much higher, according to the company's chief executive, Dr Igor Fisch. The platform involves joining a controlling sequence called a Matrix Attachment Region (MAR) to the gene of interest, which enhances its transcription.
"If you were to examine 10 transgenes in a transfected cell, you would find that only one to three of those actually function. With our MAR technology, all 10 of them will be active," he said.
The MAR element holds the transfected gene in an open chromatin state, meaning that it is always available for transcription. The net result of this is that gene amplification steps usually carried out with chemical agents such as methotrexate is not required.
"Using Selexis technology, it is necessary to screen only 50-200 clones to arrive at a suitable cell line for production, a process that takes about 6-10 weeks," commented Dr Fisch. "With conventional approaches you need to screen 2,000-5,000 clones, and if a couple of rounds of amplification are required, this process can take eight to 12 months."
This could make a big commercial difference for a product, and could mean it beats competitors to the marketplace and benefits from an extra year of patent protection (leaving aside the present difficulties in developing generics of biological drugs).
Using Chinese hamster ovary cells, a commonly used cell line, Selexis can achieve expression levels in the order of 20-40 picograms per cell per day, a 10-fold increase on the 0.5-3 pg/cell/day possible at present.
For Diosynth, this should mean more protein is made per batch, reducing the cost and hiking the efficiency of manufacturing, allowing it to compete more favourably with its competitors. At present, the most likely use of the new technology is in the manufacture of monoclonal antibodies, and particularly those that present development challenges because of poor expression yields.
Furthermore, MARtech could also be used to expand the range of proteins that can be made in mammalian cell culture, according to Dr Fisch. He noted that it makes it easier to manufacture enzymes in this way, for example.
Diosynth said it is evaluating the technology at present, with a view to incorporating MARtech into its process development activities, which would provide a revenue stream for Selexis.
Selexis was formed in 2001 and has raised about SF1 million in private funding to date, with some revenues already being made from the sale of its technology. The company had also been working on drug discovery, focusing on prostate cancer, but has shelved this project until next year while it focuses on applying MARtech to protein production.
