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Monsanto Advances Topical RNAi Pesticide Against Colorado Potato Beetle

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NEW YORK (GenomeWeb) – Ag-bio giant Monsanto this week announced that its an RNAi-based pesticide for the control of the Colorado potato beetle (CPB), a pest that attacks potatoes and other solanaceous plants, has advanced out of the discovery stage and will now undergo formal product development.

The CPB program marks the most advanced effort in Monsanto's so-called BioDirect pipeline, which centers around the use of topically applied RNAi-based treatments for pest, weed, and disease control in crop plants.

Monsanto is separately developing a transgenic strain of corn, dubbed Smart Stax Pro, that kills corn rootworms by expressing widely used Bt proteins derived from the bacterium Bacillus thuringiensis along with dsRNA designed to silence a gene essential to the insects. That product entered the company's final stage of development early this year.

BioDirect was unveiled in 2012 as a way for Monsanto to apply RNAi to crops for which the development of transgenic plants isn't economically viable. Already, Monsanto has introduced one product developed using the gene-silencing technology — soybeans called Vistive Gold that are altered with RNAi to have lower levels of saturated fats — and the firm expects Smart Stax Pro to hit the North and South American markets as soon as 2017.

But the development and launch of such genetically engineered plants is an expensive process, and therefore is typically reserved for large-acre row crops, Robert McCarroll, vice president of global chemistry technology at Monsanto and head of the BioDirect initiative, explained.

The development of RNAi-based plant treatments that are applied topically "allows you to bring the value of RNA-based biological protection into crops that can't economically support the development of the transgenic trait," he told GenomeWeb.

While Monsanto has a number of active BioDirect programs, the CPB project is the first to move into what the company calls phase 2 development.

Phase 1 is a proof-of-concept stage, and when it comes to BioDirect, this is the period when a lead RNAi molecule is identified, bioinformatically predicted to be specific for a target organism, and evaluated in limited field tests, McCarroll said. He declined to disclose the gene being targeted in the CPB program, but said that it is essential for the insect's viability.

With that work complete, Monsanto is now focusing on product formulation and the generation of safety data required by regulators.

"During Phase 2, we identify the other components that go [into a final product] in order to make it rain-fast … [and] stable under agricultural conditions," he said. In terms of safety, in phase 2 Monsanto will, among other things, experimentally validate that the product's effects are limited to the CPB. According to Monsanto, phase 2 typically lasts 12 to 24 months.

During a conference call held to discuss Monsanto's fiscal first-quarter 2015 financial results, CTO Robert Fraley highlighted the success the company has had in the CPB program thus far. He noted that in initial field tests it has demonstrated protection against CPB, with reduced larval infestation and plant defoliation, on par with standard chemical treatments.

McCarroll noted that the CPB BioDirect product is expected to be used in combination with existing chemical treatments rather than as a replacement for them, as pesticide rotation is an established approach to combating insect resistance, which has become a particularly pressing problem when it comes to the CPB.

Though the CPB program is the farthest along, Monsanto continues to make strides with its other BioDirect projects. These include an effort to develop a spray that can control weeds resistant to the herbicide glyphosate; a topical product to prevent tospovirus infections in specialty crops; and a topical treatment for bees to fight varroa mites and various viruses.

"There has been exciting progress" in these programs, McCarroll said, "but it is not yet time to declare phase 1 complete. We have more work to do towards better efficacy and selection of the final RNA molecules."

Also during this week's conference call, Fraley disclosed that Monsanto is developing a version of its DroughtGard Hybrid corn, which combines germplasm selected for drought-tolerance characteristics with a drought-tolerant biotech trait, to include the RNAi component of Smart Stax Pro.

DroughtGard Hybrid/Smart Stax Pro project is now entering phase 3, a one-to-two-year effort that involves trait integration, field testing, and regulatory data generation.

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