Gene Silencing To Boost Biological Drug Yields

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Main Category: Pharma Industry / Biotech Industry
Also Included In: Genetics
Article Date: 23 Nov 2009 - 2:00 PDT

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An American biotech company is planning to use a new technique called RNA interference (RNAi) to boost yields of biological drugs by improving the performance of drug-producing cell cultures.

Biological drugs, also called "biologics", including protein-based drugs, monoclonal antibodies and vaccines, are made in bio-reactors containing cultured lines of living cells.

Alnylam Pharmaceuticals of Cambridge, Massachusetts is setting up a new venture called Alnylam Biotherapeutics to develop RNAi technology and partner with drug companies to improve the cell cultures they use for making biologics, reported Nature News.

CEO of Alnylam, John Maraganore, told the press that the company has sequenced the genome of the Chinese hamster ovary (CHO) cell, the most widely used cell line in the manufacture of biologics, a market estimated to be worth about 100 billion US dollars.

For instance, top-sellers like Amgen Inc's anemia treatment Aranesp and Roche Holding AG's cancer drug Avastin are made using CHO cell lines, reported Bloomberg.

RNAi is a new approach to drug discovery and development and was recognized by a Nobel Prize for Physiology or Medicine in 2006.

RNAi is a natural gene silencing process that occurs throughout the plant and animal kingdom. Alnylam is currently making a range of small interfering RNAs (siRNAs), molecules that mediate RNAi, to target specific diseases by stopping proteins that cause the diseases from being made.

Studies that applied the gene silencing technology to other pathways, for instance the CHO cell-death or apoptotic pathway and metabolic pathways, showed it resulted in a "40 to 60 per cent improved cell viability as compared with untreated cells", said a statement on Alnylam's website.

"We have already shown that we can harness RNAi technology to alter the cell to live longer and do more of what it needs to do," said Maraganore.

Other scientists have already shown that RNAi can vastly increase the protein yield of CHO under lab conditions. However, as Zhiwei Song, an engineer at the Bioprocessing Technology Institute in Singapore told Nature News, the challenge is to replicate this success on a much larger scale. For example a bioreactor holds tens of thousands of CHO cells.

Biologics manufacturers are watching this development with great interest, for it would be very useful to have a way to increase protein expression in cell lines without having to change the master cell banks.

Janice Reichert, senior research fellow at Tufts Center for the Study of Drug Development in Boston, Massachusetts, told Bloomberg that anything that can reduce the time it takes to produce from the cell line, or that improves the efficiency of the process would be a good thing.

"CHOs are the default option for biotech drugs, they're the workhorse of the industry," she said.

However, as Derek Ellison, who is the chief operating officer of Eden Biodesign, based in Liverpool, UK told Nature News, Alnylam would have to show that RNAi doesn't introduce impurities or alter the quality of the drug that goes into the patient.

Others say that RNAi should be used to improve the quality and potency of biologicals, and not focus just on yields.

Maraganore said Alynlam is starting to do that.

Using RNAi technology, the company is already developing treatments for a type of lung infection, liver cancers, Huntington's disease, and amyloidosis, reported Bloomberg. One of its new drugs, developed in partnership with another biologics company, has reached the second of three stages of clinical trials required for US regulatory approval.

Sources: Nature News, Bloomberg, Alnylam Pharmaceuticals.

Written by: Catharine Paddock, PhD


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