Mushrooms sprout drug-producing powers

By Katrina Megget (2007)

The simple, run-of-the-mill, salad-variety mushroom has upped its super powers to become a potential future disease-busting hero, according to US researchers.

A genetic modification is all it would take for the common button mushroom (Agaricus bisporus) to become the new Superman as a therapeutic protein-producing factory, taking the wind out of conventional cell lines.

Researchers at the Pennsylvania State University have been able to successfully insert and express an undisclosed drug in mushrooms, paving the way for the mushroom to enter the $60bn biopharmaceutical market.

“There has always been a recognized potential of the mushroom as being a choice platform for the mass production of commercially valuable proteins,” Penn State professor of plant pathology Dr Charles Peter Romaine said.

“Mushrooms could make the ideal vehicle for the manufacture of biopharmaceuticals to treat a broad array of human illnesses. But nobody has been able to come up with a feasible way of doing that.”

Until now, that was.

To create transgenic mushrooms, the researchers attached a gene that conferred resistance to the antibiotic hygromycin into plasmids, circular pieces of bacterial DNA.

Mixing small pieces of the mushroom’s gill tissue in a flask with the altered bacterium allowed the bacterium to transfer a portion of its plasmid out of its cell and into the mushroom cell, where the introduced gene integrated into the chromosome of the mushroom.

When exposed to hygromycin, those mushroom cells containing the hygromycin resistant gene survived while normal cells were killed off.

“There is a high probability that if the mushroom cell has the hygromycin resistance gene, it will also have the partner [therapeutic protein] gene,” Romaine said.

The degree of gene expression ultimately depended on where the imported gene landed in the mushroom chromosome, among a complexity of other factors, but Romaine and his colleagues touted the discovery as an advance on conventional techniques.

The technology, though in its infancy, comes at a time when the biopharmaceutical industry is estimated to reach the $90bn mark, at least, by 2011, and the demand for insulin, faster vaccine production, and genetic disease treatments is at a high.

“Right now medical treatment exists for about 500 diseases and genetic disorders, but thanks to the human genome project, before long, new drugs will be available for thousands of other diseases. We need a way of mass-producing protein-based drugs, which is economical, safe, and fast. We believe mushrooms are going to be the platform of the future,” Romaine said.

Currently, therapeutic proteins are produced in a variety of cell lines, including, yeast, bacteria, animal and human. Plants are being explored and chicken eggs are the mainstay for the production of vaccines.

Romaine described the mushroom technology to as a “more evolutionary than revolutionary concept”, but the advantages were staggering.

“The mushroom produces a mass of bio-tissue and produces it rapidly and cheaply and in a highly contained environment. You don’t need lights like a greenhouse crop, which are expensive. It’s a whole new realm that’s untapped and unexplored with vast potential,” he said.

Using mushrooms could save upwards of millions of dollars on bioreactors for cell cultures, while a kilogram of mushroom tissue would cost just $1.50 in the US.

A crop from which drugs could be extracted could be ready in weeks because of the short propagation time, compared to some of the conventional months-long methods.

Meanwhile, the threat of animal pathogens, such as mad cow disease and Simian Virus 40 (SV40), getting into drugs would be reduced, and there were no diseases associated with mushrooms that would affect humans, he said.

There would also be no threat of genetic modification cross contamination with food crops because of the contained and isolated cultivation of the mushroom, which could easily grow in caves if need be, Romaine said.

The largest expense, according to Romaine, would be harvesting, though an automated system would cut costs.

Protein extraction, involving the squashing of the mushrooms to release the proteins from the cells, could also be costly, he said, but research was underway to address this problem.

Protein yield had yet to be studied.

Further studies of the technology are planned with funding from an undisclosed source.

Prospero Therapeutics, a Warwick University spin-out company, reported it has also invented a protein production platform based on mushrooms.

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