Over The Horizon

Gene Therapy Switch

Innovative gene therapy work in the United States is getting a helping hand from Industrial Research's biotechnology process development team.

Industrial Research has been contracted to produce large quantities of a small molecule drug, rapamycin, which will be used for clinical trials on human volunteers by US biotech company ARIAD Pharmaceuticals. Rapamycin is a very high value drug, with one gram currently worth thousands of dollars.

Two years ago ARIAD reported that the rapamycin molecule can be used as a switching-on mechanism in gene therapy trials for treating chronic diseases. For example, if a person is known to have human growth hormone deficiency, a gene cassette containing engineered human cells could be put into their body. The efficient genes would produce the lacking bioactive substance. Oral doses of a derivative of the rapamycin molecule are given to the patient to switch the appropriate genes on and off as required.

The rapamycin molecule is produced by a soil-borne organism, which is grown in Industrial Research's bioprocessing facility. The molecule is isolated and purified using solvent chromatography with 95% pure material being achieved. The whole process takes about six weeks with everyone in the process development team putting in some time, says Industrial Research's process development manager Julian Davies.

"You can't just go out and buy rapamycin off the shelf in the quantities needed for pharmaceutical purposes, which is one reason why it commands such a high price."

There are only one or two other places in the world which make the molecule. The small amount of pure rapamycin which is extracted from the volume of fermentation medium also helps explain the high cost of the molecule.

"It's a bit like extracting a needle out of haystack. From 1,000 kilograms of fermenting medium we can extract just 50 grams of rapamycin, or 50 parts per million," says Davies.

The research team is now trying to improve the strain to increase the yield to a kilogram per batch. Microbiologist Sarah Reader is working on mutating the organism and isolating a better strain, a process which will probably take about six months.

It was the unique combination of bioprocessing and chemical processing/solvent extraction facilities under the one roof which first prompted ARIAD to approach Industrial Research five years ago. There are no similar contract facilities in the US.

The initial contract was to produce five grams of the rapamycin molecule, for which the whole process had to be developed at Industrial Research. This was followed by two contracts for 30 grams each, with an order in the offing for much larger quantities in preparation for planned clinical trials.

However, the patients which the rapamycin is destined to help will have to wait quite some time before the new technology is available. At least five years of clinical trials are required to prove its safety and efficacy. In the meantime Industrial Research is weighing up its options as demand for the rapamycin could mean that either a larger facility is built to produce it or the technology is licensed to another fermentation manufacturing company.