Tuesday, April 29, 2014

Biotechnoloy Update- RNAi as a New Technology for Pest Management — by Michael Braverman, Biopesticide and Organic Support Program Manager

Most people have heard of genetically modified crops and the use of biotechnology for crop pest management. The most common of these technologies is the use of genetic material from Bacillus thuringiensis (Bt) to code for the production of a protein in plants which controls certain insects. Because of the history of biotechnology coming through the microorganism Bt, these products are considered to be biopesticides. These are commonly referred to as Plant Incorporated Protectants (PIPs) and are regulated in EPA’s Biopesticide and Pollution Prevention Division¹. A newer form of biotechnology based biopesticides is RNAi technology.

How can this technology be used?

The term RNAi stands for RNA interference because it interferes or silences processes such as protein synthesis. Without certain proteins, pests may not develop, certain processes cannot continue and so the process or the organism fails to function or reproduce. There are
many potential applications of this technology such as controlling insects, diseases and nematodes, insect transmitted diseases and reversing pesticide resistance. Just like one’s genetic makeup, this technology is highly specific. One of the newer approaches to RNAi based technology has been delivery of dsRNA through feeding insects. IR-4 first met with EPA about RNAi technology in 2008 with a company called Beeologics which developed the dsRNA of Israeli Acute Paralysis Virus of honeybees. This technology was more closely aligned with the FDA regulatory framework and was partnered with IR-4’s sister program IR-7.

How does it work?

RNAi is the name of the process but it is double stranded RNA that does the work. All plants and animals contain RNA which is part of the genetic system which serves several functions depending on the life stage. RNA is normally single stranded, not double stranded. One of the main functions of RNA is in protein synthesis which involves several steps. A single strand of messenger RNA (mRNA) is made off of the template provided by DNA. The mRNA then causes amino acids to form chains in the exact order to produce a certain protein. RNAi interferes between these two processes by interfering with or cutting up the target mRNA (see graphic for further details). The result is that the proteins are not formed and unmodified genes are only interfered with or silenced.

While most current biotechnological traits involve incorporating specific genetic material into the plants genome, some RNAi based technology can be incorporated into plants or sprayed onto plants and it does not modify the plant genome itself. RNAi is also referred to as double stranded RNA (dsRNA) technology since the interference is actually initiated due to the presence of dsRNA and it is the dsRNA that is applied or functions. This is achieved through the application of double stranded RNA. Although the technology is new, humans consume RNA every time they eat a plant.

Other biotechnology efforts.

IR-4’s biopesticide program has already successfully assisted in the registration of HoneySweet Plum, a USDA discovery which utilized a viral coat protein for resistance to plum pox virus. For several years Hawaii has been growing papayas which are resistant to papaya ringspot virus. The University of Florida has developed a similar technology incorporating resistance into papaya varieties suited to growing in Florida. In both of these cases there are simply no pesticides available that can be sprayed on plants to control viruses.

Actually, IR4’s history of involvement of biotechnology goes back to 1999 with some initial development of biotechnology based weed management in vegetables. Some of the newer areas of biotechnology projects very recently initiated involve disease management in tree nuts and ornamentals. Most biotechnology traits have been delivered through transformation via Agrobacterium, selection of transformed cells and regeneration through tissue culture. A newer technology being assisted by IR-4 involves the delivery of traits through the priming of seeds. The current focus is for management of Fusarium crown rot on tomato in cooperation with Morflora’s TraitUP technology².

How is RNAi technology regulated by EPA?

EPA’s Biopesticide and Pollution Prevention Division has a long history of regulating transgenic crops that are Plant Incorporated Protectants. EPA does not have an existing set of regulations for RNAi technology, but they are in the process of being formed. EPA recently held a Science Advisory Meeting to discuss the formation of regulations for RNAi technology. The regulations are likely to be similar to those currently used for Plant Incorporated Protectants (Genetically Modified Crops). There may be greater emphasis on environmental fate since some are sprayed onto plants or may be mobile within insects or other organisms although data indicates that RNA is rapidly degraded. RNAi technology regulation may be based on the way in which they are delivered and their intended activity and specificity. Overall human health impacts from insect or plant disease organism-targeted dsRNA is of less concern in humans due to RNA specificity and enzymes in our blood and stomach which rapidly degrade RNA.

¹EPA history of regulation for genetically modified crops. www.epa.gov/pesticides/biopesticides/pips/index.htm

²MorFlora Agro www.morflora.com//userfiles/file/Morflora-Wins-Agrow-Awards.pdf


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