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Divergence, AviGenics Awarded SBIR Grants for Agricultural RNAi Projects

The National Science Foundation this month issued phase I Small Business Innovation Research grants to two companies looking to use RNAi-based technologies to overcome key hurdles facing agriculture: parasites and disease.
The first grant, for $100,000, was awarded to Divergence to use the gene-silencing technology to create crops resistant to parasitic nematodes, specifically the lesion nematode Pratylenchus scribneri.
“Plant parasitic nematodes annually cause damage of $8 billion in the US and are among the most difficult plant pathogens to control,” James McCarter, president and CEO of Divergence, wrote in his company’s grant abstract. “Transgenic crops have a significant opportunity to provide economic benefit to growers through improved yields and decreased input costs, [as well as] to replace toxic nematicidal pesticides.”
McCarter added that corn could likely benefit from the technology.
The second grant, worth $97,415, was issued to AviGenics to help the company use an approach to develop transgenic poultry resistant to avian influenza.
“Poultry are vulnerable to [avian influenza] infections that can rapidly reach mortality rates approaching 100 percent,” Leandro Christmann, director of transgenic technology at AviGenics, wrote in his firm’s grant abstract. “Current vaccines provide only limited protection, with prophylaxis based on surveillance and diagnosis, followed by rapid depopulation and disposal of infected or exposed birds and quarantine and disinfection of farms and equipment.
“RNAi technology is a new strategy that could be applied to the inhibition of [avian influenza] virus replication, representing a paradigm shift in the way to deal with the challenges” of the virus, he added.
Both grant projects are set to begin July 1 and run until the end of 2007.
Officials from neither company were available for comment by press time.
Divergence first began using RNAi in 1999 as a way to identify nematode genes that would make good targets for nematicides, but the St. Louis-based company later began exploring whether the gene-silencing technology could be used directly as a way to control the parasites (see RNAi News, 3/19/2004).
To support this effort, the company recently received $100,000 from the NSF to develop plants that express dsRNA designed to inhibit genes essential to P. scribneri.
First, Divergence plans to select, clone, and sequence P. scribneri gene targets that are likely to be essential in all lesion nematodes. The company will then evaluate the potency of dsRNAs against these targets in a so-called hairy root system, which is essentially a transgenic plant in which the RNAi molecules are only expressed in the roots.

“Transgenic crops have a significant opportunity to provide economic benefit to growers through improved yields and decreased input costs, [as well as] to replace toxic nematicidal pesticides.”

“At the conclusion of [these experiments], it is anticipated that several target genes demonstrating reduction in lesion nematode reproduction will be selected for … whole plant transformation,” McCarter wrote in the grant abstract. “A likely crop for the first introduction of transgenic lesion nematode resistance is corn, one of the largest acreage and most valuable crops in the US.”
If Divergence’s efforts are successful, they could ultimately lead to a reduction in the need for extensive pesticide use while offering a key weapon against “an aggressive parasite that affects the production of corn,” he added.
Since cases of avian influenza infection in humans began to surface in the late 1990s, the development of strategies to deal with outbreaks of the virus has become increasingly important.
A handful of key players in the RNAi field have been looking to the gene-silencing technology for answers, but these efforts mostly involve developing human therapeutics against the H5N1 virus.
Athens, Georgia-based AviGenics, however, sees an opportunity to use the gene-silencing technology in animals to head off infection before it starts.
According to the company’s grant abstract, it plans to generate avian leukosis virus vectors that express siRNAs against key avian flu genes. The company will then establish stable cell lines hosting the siRNAs vectors in which to test the efficacy of the RNAi approach.
“Three siRNAs shown to effectively inhibit [avian influenza] viruses will be used to generate cell lines, which will be challenged with 5 different [flu] viruses to determine whether these vectors, when integrated into the avian genome, can effectively inhibit [the] viruses,” Christmann added in the abstract.
AviGenics expects that its efforts will “improve the biosecurity of biopharmaceutical production in poultry as the avian influenza virus spreads, [as] well as potentially protecting the food supply from natural as well as bioterrorist threats should these transgenic chickens gain wide approval in the marketplace,” he wrote.

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