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Monsanto Using RNAi to Target Intracellular Trafficking Gene to Fight Corn Rootworm

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Aiming to head off potential resistance to its existing corn rootworm-control technology, Monsanto is advancing a new strain of corn that uses RNAi to silence a gene involved in intracellular trafficking to combat the pest.

An exact timeline for the product's development has not been made public, but a Monsanto official told Gene Silencing News that the company aims to have it on the US market "by the end of the decade."

The corn rootworm is one of the most significant threats to corn crops, with the mature insect feeding on the primary roots of the plants and larvae consuming the root hairs and small roots. To control the pests, Monsanto and other companies have developed transgenic corn varieties that express Bt proteins derived from the bacterium Bacillus thuringiensis.

Monsanto's latest Bt trait against corn rootworm, called Cry3Bb1, was launched in 2003 and continues to provide "significant value," according to William Moar, corn insect resistance management technical lead at the company.

Still, farmers and others have raised concerns over the emergence of insect resistance, he said, leading Monsanto to strike a deal with Dow AgroSciences in 2007 under which the companies inked a deal to create a new strain of corn called SmartStax, which combines Cry3Bb1 with Dow's Cry 34/35 Bt traits.

Despite the ongoing success of SmartStax and the effectiveness for resistance-mediation strategies such as crop rotation, Monsanto is taking preemptive steps to avoid the possibility that corn rootworms will adapt to Bt traits with the development of a new corn strain — called corn rootworm III — that incorporates dsRNA targeting the insect's version of the gene Snf7.

(Monsanto and Dow AgroSciences signed a cross-licensing deal earlier this year that includes corn rootworm III.)

There had been indications that Monsanto was targeting Snf7 with its new corn product, but company officials declined to confirm this in previous interviews with Gene Silencing News.

But at the Entomological Society of America's Entomology 2013 meeting earlier this month, Moar confirmed that corn rootworm III would comprise SmartStax and dsRNAs against Snf7, in part due to company research indicating that knocking down the gene is lethal to corn rootworms but not to other insects that would likely encounter the transgenic plants.

Last year, Monsanto scientists published a report in PLoS One showing that dsRNA could be taken up in the cells of corn rootworms after ingestion and spread beyond the insects' midguts. The team also reported that Snf7 ortholog, dubbed DvSnf7, is an essential component of cellular machinery — called ESCRT III, or endosomal sorting complex required for transport — that is involved in such processes as the sorting of cell membrane receptors. Suppression of DvSnf7 with dsRNA resulted in corn rootworm mortality several days after ingestion, according to the paper.

Earlier this year, the Monsanto group published the results of a study examining the insecticidal activity of DvSnf7 dsRNAs, finding that its spectrum of activity is "narrow."

Also driving Monsanto's interest in combining RNAi with Bt traits is the complementarity between the two modes of action, Moar said.

The SmartStax approach results in a quick death of the corn rootworm, while mortality from ingestion of DvSnf7 dsRNAs typically takes five to six days. "When you combine the two together, you get a quick kill from the Bt and a chronic kill with DvSnf7," he said.

Further, the Bt approach tends to only be effective against corn rootworms in the first of its three instars, Moar added. "So if it's already fairly big or for whatever reason can escape to the second instar, the Bt [traits] aren't going to kill it." The RNAi approach, however, is lethal to rootworms at all instars.

Before Monsanto can get corn rootworm III onto the market, however, the company still needs to conduct additional research on the product examining, among other things, the potential for pest resistance, Moar said.

"We can't predict what an insect is going to do and they prove us wrong all the time," he said. "Our focus is to … go out into the field, do heavy selection ... and let the insect tell us how it is going to develop resistance … [so that we can] figure out how to overcome it."

Such work "takes a lot of time and energy," he cautioned, and so Monsanto is not offering guidance on corn rootworm's commercialization beyond saying that it hopes to have the product on the market by 2020.

According to Monsanto, the product is under phase III development, which includes advanced development activities including trait integration, field testing, and regulatory data collection. It said that this phase typically take between one and two years to complete, after which there are roughly one to three years of additional testing and regulatory preparation.

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