North Carolina State University News Services Campus Box 7504 Raleigh, NC 27695 (919) 515-3470 huup://www.ncsu.edu/news/

Media Contacts: Dr. Anne-Marie Stomp, 919/515-7572 or [email protected]

Ken West, Biolex Inc., 919/942-6748

Sara Frisch, News Services, 919/515-3470 or [email protected]

Dec. 8, 1998

NC State Start-up Bets on Duckweed for Human Protein Production

FOR IMMEDIATE RELEASE

A North Carolina State University scientist has developed the first procedure to genetically engineer duckweed, a common aquatic weed, to produce therapeutic proteins like insulin.

Dr. Anne-Marie Stomp, associate professor of forestry at NC State, has applied for a patent on the technique and launched Biolex Inc., the first plant biotechnology company to grow out of NC State laboratories. In addition to a license for the patent-pending technology, the company now has the backing of major venture capital funds.

The market for pharmaceutical proteins like insulin is worth about $10 billion yearly, Stomp estimates. In a few years, when patents on the oldest protein drugs expire, the industry will be searching for new and cheaper production techniques to counter increased competition. And with gene discovery on the rise, there will be more scientists in need of gene expression technology. Biolex can fill the gap with an inexpensive, highly controlled and consistent technology.

The gene expression and protein production technique Stomp has developed is potentially less expensive, more productive and less risky than traditional techniques using mammalian cells or tobacco and soybean plants, she says. Duckweed's rapid growth, self-cloning reproduction and relatively high protein content make it an ideal candidate for large-scale production in clean, controlled environments, she says. The resulting product would be safer and cheaper for the millions of people who take insulin, alpha interferon and other protein drugs.

"Biolex is going to turn this small aquatic plant that is considered a weed into the premier protein production system of the 21st century," she says.

Stomp's strategy is to turn the weed's oddities to her advantage. Duckweed, or Lemna, is a very curious family of plants. The tiny aquatic weed contains a lot of protein and can double in size every 24 to 48 hours by cloning itself. Each little green disk is an entire plant unit and an identical copy of its parent.

Stomp's research with duckweed is a good example of the twists and turns common to scientific discovery. After working with wastewater remediation that relied on genetically engineered trees, she sought a better technique for fighting the environment's longstanding battle with human and animal waste. Stomp redirected her interests to aquatic plants and was intrigued by the natural ability of duckweed to suck up nutrients from wastewater. She found that duckweed already was being used to treat municipal wastewater.

"What was missing was any use of genetics to improve the system. It immediately dawned on me that this plant would have fantastic potential if you could partner it with biotechnology and genetic engineering, " Stomp says. "I just switched right out of trees."

Proteins, such as therapeutics like insulin or industrial enzymes used to make stone-washed denim for jeans, can be made only by living systems. Genetically engineered duckweed could become the living system to produce these proteins, Stomp realized. However, to achieve this goal two new technologies were needed: A method to genetically engineer the aquatic weed, and efficient, versatile systems to produce it.

After years in the lab, Stomp has developed those technologies.

"Duckweed's beauty lies in its unique growth habit," she says. "It has the flexibility to grow in a variety of environments, including a stainless steel vessel, a greenhouse pool or a pond at a wastewater treatment facility." This flexibility allows duckweed to be grown in the ultra-clean, controlled conditions required for pharmaceutical proteins, as well the low-cost, large-scale production needed for industrial enzymes.

Biolex, created to capitalize on the early stages of Stomp's research, initially will use clean production techniques to make therapeutic proteins from genetically engineered duckweed. "Because of the clean technology, and because plants don't transmit human viruses, our system avoids the risk of contamination by infectuous agents," she says. "That's a major problem associated with human protein production in mammalian cells and clonal transgenic animals."

And because duckweed clones itself naturally, Stomp is confident she can create the consistent harvest necessary for efficient protein drug production.

As Stomp develops the platform technology and clean production techniques for therapeutic proteins at Biolex, her colleagues at NC State will continue related lines of research. Drs. John Classen and Jay Cheng, assistant professors of biological and agricultural engineering, and Dr. Ben Bergmann, associate professor of forestry, have a U.S. Department of Agriculture grant to develop livestock wastewater treatment systems using genetically engineered duckweed.

Dr. Yuri Yamamoto, a new member of Stomp's research lab, will continue to advance basic genetic engineering technology to keep duckweed well ahead of other protein production systems. As both technologies progress, commercial production of valuable proteins in duckweed grown in wastewater will become a reality. The systems could transform wastewater from an economic liability into a productive asset, Stomp says.

Biolex has another advantage in the market ñ exclusive use of a 1,000-strain collection of duckweed. With funding from the National Science Foundation, the collection was transferred from Switzerland and established at NC State in 1994 after its original keeper, Dr. Elias Landolt, retired. As manager of the collection, Stomp can choose duckweed samples that have high levels of protein content and other desirable traits. Already, Stomp has discovered strains that have superior characteristics for genetic engineering and for growth in animal wastewater.

"Just like having access to a collection of all the world's corn varieties is critical to corn breeders, this collection will be invaluable to our research," Stomp says.

In October, Biolex became the first venture to be funded by Centennial Venture Partners, a new NC State-connected venture capital fund created to assist growing companies with close ties to the university. Intersouth Partners IV of Durham, and Kitty Hawk Capital of Charlotte, two of the Southeast's most high-profile venture firms, joined Centennial Ventures in backing Biolex.

Stomp's business partners, president Ken West and chairman and CEO Dr. Bob Erickson, have decades of experience in the biotechnology and pharmaceutical fields. "It's great to work with such a strong business team and the research strengths of NC State," Stomp says.

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NOTE TO EDITORS: Color photos of Dr. Anne-Marie Stomp and close-up color slides of duckweed are available from NC State News Services by calling (919) 515-3470. For high quality, digital images, contact Roger Winstead of NC State Creative Services at (919) 513-1463 or [email protected].