Plants already have the tools to respond to a range of biotic and abiotic threats. The problem, says North Carolina-based startup Upstream Biotechnology, is that genes conferring disease resistance can also impose a yield penalty.
Put another way, if a plant is constantly producing proteins to tackle threats, it’s expending energy that could otherwise go into growth.
Founded on research into plant immunity out of Professor Xinnian Dong’s Lab at Duke University, Upstream introduces a molecular gate or “SwitchBlade” that activates defenses only when and where they are needed,
As a result, Upstream can “address one of the central tradeoffs in crop biotechnology: improving disease resistance without imposing the yield penalties often associated with constitutive defense activation,” claims cofounder and CEO George H. Greene PhD.
“The platform regulates trait activation at the level of protein translation, enabling plants to activate resistance traits in response to disease or stress while maintaining normal growth under non-stress conditions,” adds Greene, who has just raised a seed round led by LeVert Ventures, with participation from Corteva Catalyst, Silver Blue, VTC Ventures, and others.
During normal conditions, the gene’s instructions may be present, but the SwitchBlade tech largely prevents them from being translated into defensive proteins, says Greene. When disease or other stressors are detected, however, the gate is released, allowing the plant to produce the protein and activate its defenses only when needed.
“Upstream is developing a differentiated platform that could become an enabling technology for disease resistance and crop resilience across multiple crops. The company’s science is rooted in world-class plant immunity research, and its partnership-driven model aligns well with how major seed companies evaluate and deploy new trait technologies.” Karen LeVert, managing partner, LeVert Ventures
Switching defenses on only when they are needed
The new tranche of capital will be used to advance the SwitchBlade platform, expand validation across more crops, strengthen IP, and support collaborations with seed industry partners, Greene tells AgFunderNews.
While plants have evolved to develop defense mechanisms to tackle threats, there is no particular evolutionary advantage in doing that on a selective basis, points out Greene. “Plants don’t really care if you’re getting 40 bushels an acre versus 20. The job for the plant is to simply survive to the next generation.
“We’re using the plant’s natural [disease resistance] traits and adding a new control layer on top to improve how those traits perform. Our tech controls when an existing genetic message is translated into protein, which means in normal conditions trait activation is low, but when the plant needs to respond to stress, it turns on and increases the trait activation at the appropriate time. So you’re really controlling when and where the defense response is triggered in the plant so you get the benefit with none of that metabolic drag.”
The defensive response is also localized, which further prevents yield drag, he added. “That is another key component of what we’re doing. Other approaches focus on systemic activation, asking the whole plant to defend itself, even though the whole plant isn’t experiencing the stress. Our technology is really focused at the site of the infection or abiotic stress.”
Tech can be deployed across multiple crops
According to Greene, the tech can be applied to multiple crops from soy, corn, and rice to tomatoes. It can also be used on multiple pests from Asian soybean rust and other fungal foliar pathogens to abiotic stress (drought, heat etc) or bacterial pathogens.
“There is some customizing that would need to be done for each switch, but we’re not starting from scratch each time,” he explains. “It’s more about tweaking, adapting, and refining the system when we look at a different crop target or indication.”
‘We are the control layer, not the finished product’
How the tech is regulated depends on the application and would be worked through with seed companies Upstream is partnering with, says Greene. In some cases, for example, partners might introduce a disease resistance gene in tandem with Upstream Bio’s SwitchBlade tech.
“We are the control layer and expression system, not the finished product. The SwitchBlade platform translation control doesn’t necessarily care what background gene you’re using.”
The business model
Historically, regulating where and when messenger RNA is used to make a particular protein “has been difficult,” says Greene. “But this is where the 30 years of research at Duke [University] has de-risked the platform. Where we see ourselves as unique is the ability to use translational control to respond to environmental challenges.”
He added: “To date, we’ve demonstrated efficacy across multiple row crop systems and we’re advancing programs across row crops and specialty crops for biotic and abiotic stress.”
The business model is to license the tech to seed companies although the firm could also potentially develop traits in-house and license those, he says.
“We’re not doing gene discovery [for disease resistance]. These seed companies have their own sets of traits that they know are valuable, but they need to be perfected based on timing and performance. We’re providing the ability to fine-tune translational control for precise trait activation, which could drive real value.”
Further reading:
🎥 Can editing the ‘dark genome’ make crops more heat tolerant?
Resurrect Bio expands Series A to $10.3m to scale tech helping plants to defend themselves
Phytoform partners with major seed breeders to bring AI-powered plant design to corn crops
🎥 Digital twins: Heritable Ag combines AI, genomics and environmental data to slash R&D timelines
