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From: Laurel Hopwood <[log in to unmask]>
To: CONS-SPST-BIOTECH-FORUM <[log in to unmask]>
Sent: Sun, Feb 23, 2014 1:04 am
Subject: Gene-Silencing Pesticides



Gene-Silencing Pesticides
Chemical & Engineering News - 17-Feb-2014
Regulators prepare for next wave of pesticides based on RNAinterference
(edited)


When farmers began seeing increased damage from the western cornrootworm a few years ago, they knew that the beetle was developingresistance to a widely used toxin produced by the bacterium Bacillusthuringiensis (Bt). The approach of GE corn to produce Bt toxin waslosing its effectiveness against the insect.
 
Monsanto raced to find an alternative weapon to combat thedevastating pest. The company is now close to seeking regulatoryapproval for a strain of corn engineered to produce double-strandedRNA (dsRNA). When a rootworm larva eats the roots of the corn, itingests dsRNA, which silences an essential gene in the pest, therebykilling it.
 
The approach relies on a biological process called RNAinterference (RNAi), which is used by cells to suppress geneexpression. The process is triggered by dsRNA, which cells break intopieces that interfere with the transcription of messenger RNA and thetranslation of that mRNA into protein.


But some scientists are raising concerns about the potentialrisks of the technology to nontarget organisms, includinghumans.
 
The EPA held a meeting last month to get advice from experts onwhether its current framework is adequate for assessing the risks ofthe new technology. These experts and others say that regulators mustbetter understand the toxicity issues unique to RNAi-based pesticides,as well as the persistence of dsRNA in the environment.
 
EPA has some experience examining the risks associated withRNAi-based pesticides, but most of the products were reviewed beforescientists had a good understanding of the RNAi process, says ChrisWozniak, a biologist with EPA's Biopesticides & PollutionPrevention Division. The first RNAi-based pesticides were approved byEPA in 1997 for targeting infectious plant viruses, but the mechanismbehind RNAi was not widely understood until 1998 (Nature, DOI: 10.1038/35888).


EPA acknowledges there is insufficient data in the publishedliterature on the stability and activity of dsRNA in soil and aquaticsystems to determine how long a dsRNA molecule will last in theenvironment. Its lifetime could depend on the size of the molecule,whether it is in a clay soil or a loamy soil, and whether it binds toorganic matter or other soil particles, Wozniak says.
 
Thus far, all of the RNAi-based pesticides reviewed by EPA haveused a similar strategy: They require incorporation of the pesticideinto the plant genome to be effective. But companies are also workingon RNAi-based products that are intended to be directly sprayed onplants, insects, or other pests, or applied in granular form. Suchproducts could be mixed with surfactants, stabilizers, and otherpesticide active ingredients.
 
Monsanto is currently developing an RNAi-based spray designed tomake weeds less resistant to its herbicide Roundup. Syngenta acquiredthe Belgian biotech company Devgen in late 2012 to work on RNAi-basedpesticide sprays.
 
The EPA does not have any experience with hazard and riskassessments for dsRNA products that are applied directly to theenvironment, says Russell Jones, a senior biologist in EPA'sBiopesticides & Pollution Prevention Division.
Some of the hazards that are unique to dsRNA active ingredientsinclude off-target gene silencing, silencing of the target gene inunintended organisms, immune system stimulation, and the saturationand disruption of the RNAi machinery in nontarget organisms, Jonesnotes. These hazards were first pointed out by USDA's entomologistsJonathan G. Lundgren and Jian J. Duan in a BioScience paper last year(DOI: 10.1525/bio.2013.63.8.8).
 
The USDA scientists also highlighted areas where information islacking, including the persistence of dsRNA in the environment.Without such information, it is difficult to assess exposure.


Much of the concern related to human health effects of dsRNA wasraised after a study led by Chen-Yu Zhang of Nanjing University, inChina, that reports the presence of exogenous plant micro dsRNA inhuman blood plasma after the consumption of rice (Cell Res. 2012, DOI:10.1038/cr.2011.158).The paper stoked concerns about the safety of RNA-based technology infood.


Beekeepers are urging EPA to thoroughly evaluate RNAi designed toprotect crops to look for unintended effects on nontarget organismssuch as bees.


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