As part of its ongoing investment in agricultural RNAi, Monsanto has established a company to develop new approaches for delivering dsRNAs based on technology originally developed at the Massachusetts Institute of Technology for use with RNAi therapeutics.
The company, called Preceres, was co-founded by MIT's Daniel Anderson and Arturo Vegas, who pioneered novel lipid-based siRNA delivery vehicles independently and in collaboration with Alnylam Pharmaceuticals. Monsanto's venture capital arm Monsanto Growth Ventures is an investor in the new firm, and Monsanto will have the exclusive rights to Preceres' discoveries and technologies.
The formation of Preceres comes amid an ever-increasing interest in RNAi by Monsanto. As reported by Gene Silencing News, in 2012 the ag-bio giant paid Alnylam almost $30 million for the exclusive agricultural rights to its technology and intellectual property. And earlier this year, Monsanto took a four-year option to license Tekmira Pharmaceuticals' lipid-based RNAi delivery technology for agricultural applications.
Meanwhile, Monsanto is just a few years away from launching Smart Stax Pro, a Western corn rootworm-resistant strain of corn that expresses widely used Bt proteins derived from the bacterium Bacillus thuringiensis along with dsRNA designed to silence a gene essential to the pests.
But with Preceres, Monsanto is looking not at transgenic RNAi, but rather its BioDirect line of topical RNAi products for insect and weed control, according to Robert McCarroll, vice president of global chemistry technology at Monsanto and head of the BioDirect initiative.
Right now, BioDirect includes three early-stage programs: a spray that can control weeds resistant to the herbicide glyphosate; a topical treatment for plants to combat Colorado potato beetle; and a topical product to prevent tospovirus infections in specialty crops. It also includes a more advanced project involving a topical treatment for bees to fight varroa mites and various viruses, which Monsanto picked up through its 2011 acquisition of Beeologics.
Although these efforts may benefit from the work being conducted at Preceres, McCarroll noted that they "don't have as much as a need for an advanced delivery agent as some of the products we anticipate developing later," particularly in terms of dose reduction.
For instance, Monsanto envisions RNAi-based herbicides and pesticides with broader spectrums of activity than the current lineup of BioDirect products, which would require a combination of different dsRNAs against different targets, he explained.
Rather than increasing the amount of product required to account for the additional RNAi payloads, which could become prohibitively expensive, the company hopes that more efficient delivery will result in increased potency and therefore allow it to do more with less.
Better delivery is also expected to help Monsanto go after pests that are not as susceptible to RNAi as, say, corn rootworms. Indeed, while robust RNAi effects are seen in a number of insects through the consumption of dsRNA, dsRNA-mediated gene silencing can be more difficult to achieve in many others — oftentimes for the same reasons that beleaguered the therapeutic use of RNAi, such as nuclease degradation.
"Different organisms are differently susceptible to topically applied RNA … [which] leads you to want to think about specialized delivery agents," McCarroll noted.
McCarroll said that Preceres would start by tweaking the RNAi delivery technologies already developed by Anderson and his colleagues for agricultural purposes. Chief among these are lipidoids, a kind of lipid nanoparticle that have been optimized for siRNA delivery.
In 2009, Anderson and collaborators at MIT and Alnylam reported on the use of lipidoids to carry siRNAs to the liver. A few years later, the MIT group published data showing that the carriers could be used to shuttle immunostimulatory RNA into immune cells. And late last year, the MIT investigators described a magnetic siRNA delivery system based on lipidoid-coated iron oxide nanoparticles.
"The initial focus of Preceres will be to apply the existing technologies represented by [the MIT IP licensed by the new company], lipidoids primarily, and then optimize it through iterative evaluation and synthesis to get to the delivery agents we need," McCarroll said.
Although it was just formed, Preceres is now up and running, he added, with its management and senior scientists on board. The firm has most of its equipment in place, and is already synthesizing compounds for evaluation by Monsanto, he said.
"We couldn't be more pleased with the speed or the progress," he said.