Dow AgroSciences publishes new data on use of RNAi against corn pest

Researchers from Dow AgroSciences recently published data demonstrating that RNAi silencing of two Western corn rootworm (WCR) genes via double-stranded RNA in adult female insects can prevent hatching of their eggs.

The findings point to a new opportunity for using RNAi to combat one of the most economically important agricultural pests, while providing insights into Dow AgroSciences' ongoing efforts to develop insect-resistant crops that incorporate the gene-silencing technology.

In addition to being developed for research and therapeutic applications, RNAi has also shown promise for its agricultural potential. Already, there are a number of foods modified with the technology on the market including a non-browning apple cleared for sale in the US earlier this year.

Transgenic plants designed to express RNAi molecules against exogenous genes — so-called plant-incorporated protectants (PIPs) — have yet to receive regulatory clearance. That could change in just a few years, however, if Monsanto meets its goal of launching a new line of WCR-resistant corn called Smart Stax Pro that expresses widely used Bt proteins derived from the bacterium Bacillus thuringiensis along with dsRNA designed to silence a gene essential to the insects known as Snf7.

But while it is leading the race for RNAi PIPs, Monsanto is not the only one in the running. Among the various ag-bio firms that have shown interest in RNAi, Dow AgroSciences has been quietly working with the technology and has its own WCR program underway.

Although the status of that work remains undisclosed, a publication appearing in Insect Biochemistry and Molecular Biology suggests that the company may have already identified the genes it aims to silence with its own dsRNA-expressing corn strain.

The combination of WCRs' susceptibility to environmental RNAi — a process wherein dsRNA can induce gene silencing in an organism after being ingested — and the estimated $1 billion in damage they cause on North American farms annually has made the pest a top candidate for RNAi intervention.

Monsanto ultimately settled on Snf7 as the RNAi target for Smart Stax Pro, finding that its suppression killed WCRs. But in the recently published study, researchers from Dow AgroSciences and collaborators at the University of Nebraska took a different tack, choosing to go after genes involved in WCR development. This approach, called parental RNAi (pRNAi), is designed to attack the pest's offspring rather than the pest itself.
The scientists constructed dsRNAs against hunchback (hb), a gap gene encoding a zinc-finger-containing transcription factor known be important for axial patterning in many insects, and brahma (brm), which encodes an ATP-dependent remodeling enzyme associated with the nucleosome remodeling that is essential for regulated gene expression.

When fed to adult female WCRs, the dsRNAs led to a significant decrease in hb and brm transcripts. Although the RNAi molecules did not appear to influence the total number of eggs the insects laid, there was an almost complete absence of hatching in the eggs from insects exposed to dsRNAs against either gene.

In addition to confirming the systemic nature of RNAi in WCRs, the findings indicate that the two genes play key roles in WCR embryonic development and could prove to be useful RNAi targets in adult rootworms that prevent crop injury by cutting the population of larval progeny of treated adults, the study's authors wrote.

Still, the researchers cautioned that additional work remains before a pRNAi-based pest-control strategy could be employed. They noted that their study involved the continuous exposure of the WCRs to dsRNAs throughout ovariole development and oviposition, which does not reflect a real-world scenario. As such, "the timing and level of exposure necessary to achieve the pRNAi response are uncertain and a more thorough investigation of dose-response relationships for pRNAi targets is necessary to fully evaluate their utility for pest management."

A spokesperson for Dow AgroSciences declined to comment on the study or the company's WCR program. However, she had previously told GenomeWeb that the company is interested in stacking RNAi with its proprietary Bt proteins in a manner similar to Smart Stax Pro.

Notably, in 2013 Dow AgroSciences forged a deal under which it gained non-exclusive access to Monsanto's RNAi technology for WCR protection in exchange for a license to a Dow AgroSciences herbicide-tolerant trait for use in field corn.