This article by Jim Lane first appeared in BioFuels Digest, Feb. 6, 2019.
If you’ve seen many World War Two thrillers about strategic bombing, you’ll know that precision, precision, precision is the goal, and smart bombs as a military technology have been in the public imagination since their first successes in Afghanistan and later in the first Gulf War, and ever since.
Think on an incredibly small nanoscale and down to the pests that threaten crops instead of the bad guys that threaten civilization, and the same transition from carpet-bombing to precision bombing is underway, and TechAccel – one of those accelerators worth paying attention to – is all over it.
Just like bombing in the military world, you need the weapon, a delivery mechanism and a high-throughput manufacturing capability. Same with pests.
What makes the effort to transform pest control particularly interesting at this moment in history is that one small-ish but highly-regarded technology accelerator, has taken on the entire supply chain — weapons, delivery and heavy manufacturing — in a signature series of investments and company formation.
And, for those who are special fans of the fast-developing world of genetics, in the area of weapons development, TechAccel has formed a company to exploit the relatively new and certainly far-out world of RNA interference, known in the community as RNAi and easily pronounceable only by Norwegians.
There are a thousand interesting things about RNA, but here’s the one you need for this story. Your DNA creates RNA in order to express your genetic code — so, if you have, say, green eyes, those genes are written in DNA but get translated into RNA before any tissue is actually produced and that green color shows up in your iris. Interfering with RNA makes it possible to suppress genes without actually changing the genetic code. It’s like removing the switch instead of re-writing the circuit.
JA Lindbo wrote a few years back. “RNA interference, or RNAi, is arguably one of the most significant discoveries in biology in the last several decades. First recognized in plants (where it was called post-transcriptional gene silencing, PTGS) RNAi is a gene down-regulation mechanism since demonstrated to exist in all eukaryotes.”
As TechAccel CSO Brad Fabbri explained to The Digest, “We like RNA. It’s very specific. It’s safe — we eat it every day. We can design it to hit one insect, unlike traditional approaches such as organophosphates, which are like carpet bombing, you’re killing a lot, including insects just wandering in there.”
“No one wants to kills butterflies and bees, and any time you kill a bunch of insects, you leave this blank area, you’ve disrupted the biome and you may find that things are way out of balance, other things can move in that weren’t there, and not the ones you wanted,” explains Fabbri. “So, RNAi can be much more specific; there’s potentially less management, and its a much more intelligent and prescriptive approach, and we just hit the things we wanted to hit.”
It’s starting to sound a little like modern cancer therapies, isn’t it? In the old days, with traditional chemo and radiation, the aim was to try and kill any rapidly dividing cells, which absolutely kills more cancer than regular cells, but you can get those really bad side effects. Something more mundane might be the use of antibiotics, which also takes a sort of carpet bombing approach — along with the bad bacteria the treatment is aiming at, there can be other, useful microbes caught in the crossfire, and that’s why, for example, people can get gastro issues when they take antibiotics.
If we could hit the bad bacteria and not the good ones, then we wouldn’t get out of balance.
As it is with you and your microbiome, so it goes, more or less, with pests in the plant biome. Smart bombs allow us the opportunity to hone in on the target.
Accordingly, it’s big news that TechAccel launched a new company out of their acceleration chambers — this one is RNAissance Ag LLC, which holds the exclusive license to RNA-interference technology in partnership with the Donald Danforth Plant Science Center in St. Louis, MO. The new company will use the proprietary technology in the development of sprayable insect control measures.
RNAissance Ag, which is pronounced “Renaissance,” was formed following successful research at the Danforth Center funded with TechAccel’s first grant in the “Path to Commercialization” Program. The Danforth Center is one of the world’s leading independent plant science research institutes.
The RNAi technology was jointly developed by Bala Venkata, Ph.D., senior research scientist and Nigel Taylor, Ph.D., associate member, and Dorothy J. King Distinguished Investigator at the Danforth Center.
As Wikipedia observes: “Cells in the midgut of some insects take up the dsRNA molecules in the process referred to as environmental RNAi. In some insects the effect is systemic as the signal spreads throughout the insect’s body (referred to as systemic RNAi). RNAi technology is shown to be safe for consumption by mammals, including humans.”
For a second, let’s rewind to our World War Two analogy, that you need high-throughput manufacturing and a delivery mechanism as well as the actual weapon.
For now, think spraying. As TechAccel’s Fabbri explains it, “particularly for [near-term] RNA insecticides it could be a spray, so that R&D doesn’t have to focus on making it systemic. The first ones on the list could be insects that chew leaves, not sucking or piercing insects (then there are more challenges). Fortunately, there are a lot of insects in that group.”
TechAccel also announced it participated in GreenLight Biosciences Inc.’s latest funding round, with an interest in collaborative research leveraging GreenLight’s technology in advancing biopesticides.
This is incredibly important to the story — the manufacturing capability. As Fabbri explained, “when we looked at RNA, you can do all this design and stuff, but the price of the active ingredient has to be in line with what farmers are normally paying. And it’s been really hard to imagine getting there, with RNA in some purified forms going for $1,000 a gram or even $10,000 a gram. Pharma can look at those prices, but not agriculture.”
“Companies have been coming forward only recently with a capability to make cheap RNA,” said Fabbri. “Biologix is one. RAAgri another. To us, GreenLight is the most interesting, and they have publicly announced that they could get to a cost at scale that’s below a dollar a gram. And this has put it in the range of commercially viable and a cost of goods a farmer would buy.”
“And once you have the active ingredient, and you’ve proven that you can spray and it doesn’t degrade, once you have design and cheap manufacturing, now you’ve made that sprayable effective,” said Fabbri. “That’s why we’re investing across delivery and manufacturing, we have a lot of the pieces and we think we can advance that efficiency.”
GreenLight Biosciences, based in Medford, Mass., is a biotechnology company developing bioprocessed RNA products for healthcare and agriculture applications, including biopesticides. The company announced its $50 million Series round last month.
There’s been an awful lot of chat about precision over the years, and the FAO tells us we’re going to have 10 billion people by mid-century and precision ag is part of how we are going to produce the food, feed and fuel. A lot of that has been in electronics, and Case and John Deere have been active there, with GPA technology, for one, allowing precision planting and application. Monsanto bought Climate Corp and there have been other big and small deals, enough to see that companies like Indigo, the Novozymes/Monsanto BioAg Alliance are a wave of the future.
But, more than planting density and precision application of nutrients — there’s an entire effort we might see based around more intelligence — being able to see the plant biome as a whole system rather than simply a plant stuck in the soil. This is not just about organic farming and pricey but chemical-free lettuce at the store where rich people go. It’s about a broader renaissance based in gathering data and assessing strategies to assist the biome to produce more of a target product without compromising the biome’s long-term viability or creating side effects because of carpet bombing approaches that burn the good villages along with knockin’ out the bad guys.
RNAi might well be a big part of that story — for sure, we need more yield. As Danforth Center president Jim Carrington observed, “Over $40 billion per year is spent on pest control, yet over 20 percent of all crops are still lost due to insect damage. This new company is evidence of an exciting new technology advancing toward market with the potential to make a major impact.”
The two actions are part of TechAccel’s broad strategy to develop safe, effective and sustainable biopesticides to address global crop losses from pests. TechAccel disclosed select additional biopesticide research and development occurring along several fronts:
TechAccel also recently announced collaborative research with AgroSpheres Inc. to explore nanotechnology in biopesticide delivery.
TechAccel, LLC, was founded in 2014 as a first-of-its-kind venture and technology development company in the agriculture, animal health and food tech sectors. TechAccel sources, invests in and acquires early-stage innovations. Through collaborations with universities and research institutions, TechAccel conducts advancement and de-risking research and development to ready technologies for commercialization.