Phytophthora sojae destroys an estimated $1 to 2 billion in US soybean production every year. Unlike foliar fungal diseases that can be managed with timely fungicide applications, P. sojae is a soil-borne oomycete that attacks roots and stems and against which fungicide options are limited. Genetic resistance is the primary management tool, and it is a tool with a documented resistance erosion problem: single-gene Rps (Resistance to Phytophthora sojae) loci have been the backbone of commercial soybean resistance since the 1980s, and virulent P. sojae races capable of overcoming each commercial Rps gene have been documented across major US production areas. ClimateCrop's soybean disease resistance program takes a different approach — targeting susceptibility genes rather than resistance genes — and this update covers what the first multi-location field evaluation showed.
The Susceptibility Gene Strategy
Conventional disease resistance programs focus on resistance (R) genes — genes whose protein products recognize specific pathogen-derived molecules and trigger an immune response. R gene resistance is often race-specific, effective against pathogen strains carrying the recognized molecule (avirulence gene product) but ineffective against races lacking it. Race specificity is the fundamental weakness: selection pressure from resistant varieties favors the spread of virulent races that defeat the R gene, and resistance erosion follows a predictable trajectory from deployment to field failure over years to decades.
Susceptibility (S) genes take a different perspective. Pathogens often require specific plant proteins to complete key steps in their infection cycle — gaining entry to the cell, suppressing the plant immune response, or accessing nutrients. These plant proteins, when present in their susceptibility-conferring form, are effectively being co-opted by the pathogen. Editing or deleting these S genes removes the pathogen's foothold without relying on recognition-based immunity. Because S gene resistance does not depend on recognizing any specific pathogen molecule, it is generally more durable — a virulent pathogen race that overcomes R gene resistance cannot simply shed an avirulence gene to overcome S gene resistance, because it would need to acquire a new ability rather than lose an existing one.
DMR6-1: The Primary Target
DMR6 (Downy Mildew Resistant 6) was originally identified in Arabidopsis as a gene whose disruption conferred broad-spectrum disease resistance. The Arabidopsis protein is a 2-oxoglutarate-dependent dioxygenase that hydroxylates salicylic acid, a key plant immune signal, converting it to a less active form. By degrading salicylic acid, DMR6 acts as a negative regulator of the plant immune system — keeping immunity suppressed under non-stress conditions to avoid the growth costs of constitutive immunity activation. Pathogens, including P. sojae, have been found to upregulate DMR6 expression during infection, essentially using the host's own immune suppressor against itself.
Disrupting DMR6 in soybean (GmDMR6-1) removes this pathogen-exploitable immune suppressor. The disrupted plants maintain elevated salicylic acid levels, creating a baseline immune readiness that accelerates pathogen detection and response. This is not costless — elevated salicylic acid can interfere with auxin and jasmonate signaling pathways that regulate growth — but the degree of growth penalty depends on the severity of the knockout and the genetic background.
ClimateCrop used CRISPR-Cas9 to generate multiple soybean events with different editing outcomes at GmDMR6-1: complete biallelic knockout events, partial-function hypomorphic events (single-nucleotide edits in the substrate-binding pocket), and promoter-edited events with reduced expression rather than complete loss of function. This event diversity was intentional: we anticipated that the complete knockout might show unacceptable growth penalties in certain environments and wanted the hypomorphic series as a fallback with a better penalty profile.
Rps Gene Engineering
In parallel with the DMR6-1 program, we evaluated CRISPR-mediated engineering of the Rps1k locus — one of the most widely used commercial Rps genes. The objective here was not simply to introduce Rps1k (which already exists in commercial germplasm) but to modify its coding sequence to broaden its recognition specificity. Structure-based protein engineering of the Rps1k leucine-rich repeat (LRR) domain — the region that recognizes the Avr1k effector protein from P. sojae — identified substitutions predicted to expand recognition to additional Avr variants. Two modified Rps1k variants, designated Rps1k-E1 and Rps1k-E2, were introduced via HDR into an elite soybean background.
Field Evaluation: 2025 Results
The 2025 multi-location field evaluation ran across six locations spanning Ohio, Indiana, Illinois, Iowa, Missouri, and North Carolina — representing the core US soybean production area where P. sojae pressure is most consistent. At each location, trials were conducted under two conditions: naturally occurring P. sojae pressure (the ambient disease load at each site), and artificially inoculated plots where infested millet seed was incorporated into the soil to ensure standardized, high-pressure disease exposure.
DMR6-1 Knockout Results
The complete biallelic GmDMR6-1 knockout events showed exceptional resistance — less than 3 percent plant stand loss under artificial inoculation at all six locations, compared to 34 to 67 percent loss in the unedited control depending on site. This is consistent with published results from other research groups working with DMR6 in tomato and potato and validates the approach in soybean. The growth penalty concern proved real but manageable: under non-disease-pressure conditions, the complete knockout events showed a 4.2 percent yield reduction relative to the unedited control, attributable to mild constitutive immune activation.
The hypomorphic events showed a more favorable penalty profile. The two hypomorphic events with single-amino-acid substitutions in the substrate-binding pocket retained 35 to 48 percent of wild-type enzymatic activity based on in vitro assays. In the field, these events showed 89 and 91 percent reduction in plant stand loss under artificial inoculation — not as complete as the full knockout but substantially protective — while showing no statistically significant yield difference from the unedited control in non-inoculated plots. This is the target profile: meaningful disease protection without yield cost under favorable conditions. The leading hypomorphic event, designated CC-Soy-DMR6-H2, advances to the 2026 field season as the priority commercial candidate.
Rps1k Variant Results
Rps1k-E1 performed as predicted: it showed expanded recognition of P. sojae races virulent on standard Rps1k. In the inoculated trials, Rps1k-E1 provided resistance against a mixed-race inoculum that included races 1, 3, 4, and 7 — covering four of the six most common virulent races in US production areas. Standard Rps1k was effective only against races for which it carries native specificity. Rps1k-E2 showed broader recognition still but was associated with an auto-immune phenotype in the Indiana and Illinois trials — spontaneous hypersensitive response lesions under non-disease pressure — which disqualifies it from advancement without further engineering to reduce the constitutive activation. Rps1k-E2 moves back to the lab for modified LRR domain engineering.
The Interaction With Climate Stress
One result from the 2025 season that was not anticipated at trial design was the interaction between drought stress and P. sojae resistance. The Missouri and North Carolina sites experienced significant water deficit during July and August 2025. Under drought stress, both the control and the edited lines showed reduced growth, but the complete DMR6-1 knockout events showed a substantially larger drought-stress penalty than the unedited control — a 9.1 percent yield reduction in stressed plots compared to 4.2 percent in the non-stressed plots at the same locations. This interaction appears to be mediated by salicylic acid-jasmonate pathway crosstalk: the constitutively elevated salicylic acid in the full knockout events suppresses jasmonate-mediated drought stress responses, amplifying drought sensitivity.
This interaction reinforces the case for the hypomorphic approach. CC-Soy-DMR6-H2, with partial DMR6-1 function retained, showed no significant drought stress interaction in the 2025 data — its yield under drought conditions was statistically indistinguishable from the unedited control under drought conditions. Disease resistance was maintained. This is the trade-off profile that a commercial variety needs: protection against the target disease without amplifying vulnerability to other stresses that will occur simultaneously in production environments.
Path to Commercial Deployment
CC-Soy-DMR6-H2 qualifies for USDA SECURE rule exemption as a base-edited event with no foreign DNA. A SECURE exemption request will be submitted in Q1 2026, and we anticipate confirmation within 90 days based on prior review timelines for similar events. Pending SECURE confirmation, the event will enter the seed multiplication pipeline for licensing to commercial soybean breeding programs in 2027.
The broader conclusion from the soybean disease resistance program is that susceptibility gene editing can deliver durable, climate-stress-compatible resistance in a commercially relevant crop on a timeline that is competitive with conventional resistance breeding. The CC-Soy-DMR6-H2 event took three years from target identification to multi-location field validation. A conventional backcross breeding program introducing a new Rps gene into commercial backgrounds typically requires six to eight years to the same stage. That timeline compression matters when the pathogens are adapting and the climate is changing simultaneously.