Gene drives – a genetic engineering approach that quickly spreads specific genetic changes throughout a population, whether to kill it off or add a new trait – may have potential for controlling weeds. But so far, gene drives have primarily been studied in mosquitoes, and have yet to be deployed in the real world.

In a first-of-its-kind study, researchers modeled how a gene drive would proceed in plants. Their simulations suggest that a gene drive’s success may hinge on seed banks – underground reservoirs of seeds that can germinate years or even decades later. Without proper consideration, they found, these stored seeds can slow down or even doom the gene drive, because they continually reintroduce plants without the gene drive into the population.

Modeling studies like this one can help scientists design successful gene drives in plants and discover and mitigate potential problems before deployment in the wild, the researchers said.

Jaehee Kim, assistant professor of computational biology in the Cornell Ann S. Bowers College of Computing and Information Science and the College of Agriculture and Life Sciences (CALS), and Philipp Messer, professor of computational biology in CALS, are co-authors on the new study, “Seed Dormancy Shapes Gene Drive Dynamics in Plants,” published April 3 in Nature Plants.

The development of CRISPR-Cas9 gene editing technology, which allows scientists to make precise changes in the genome, has made gene drives more feasible in the lab. But there are still serious concerns that they may spread to non-target organisms and cause ecological damage in the wild. 

“People have been thinking about gene drives for decades, but it was always kind of this science fiction technology,” Messer said. “With the advent of CRISPR technology, this has all changed, and the engineering of gene drives has finally come within reach. Yet there’s still some experimental questions, a lot of modeling questions, and so far, nobody has really released one.”

Recently, researchers developed two gene drive systems for plants in the lab – CAIN and ClvR – that are reliably passed down to offspring and cause the plants to produce inactive pollen, ovules or both.

“Gene drives have been suggested as an alternative control measure for weeds, but their feasibility in plant species had never been demonstrated experimentally before CAIN and ClvR,” Kim said.

Kim and Messer’s team developed a modeling framework to simulate how these two gene drive approaches would play out over time. The model considers how many viable pollen or ovules each plant produces, how long seeds survive in the seed bank and how many of those seeds germinate each year.

Seed banks are a key part of understanding gene drives in plants, Kim said, because they set plants apart from other gene drive species scientists have investigated.

The simulations predicted both CAIN and ClvR gene drives would successfully spread mutations through the population. However, the longer that seeds survive in the soil, the longer it takes for the engineered mutations to spread. Additionally, scientists may need a greater number of engineered seeds or plants to start off the gene drive, to drown out stored seeds that germinate later on.

Despite the challenges presented by a seed bank, it potentially provides a major benefit. Stored seeds may act as an “evolutionary buffer” by weakening the gene drive so it won’t take off in the wrong place.

“Even if it got accidentally released, or there was spillover to an unwanted population, a seed bank can cause it to die out naturally,” Kim said. “It acts as a natural biosafety measure.”

The researchers hope their model will serve as a foundation that will one day help field biologists plan successful, yet contained, gene drives.

“People thought that gene drives in plants really wouldn’t work that well,” Messer said. “But after this modeling study, I think plants may actually be one of the better systems to try out a gene drive.”

Isabel Kim ‘20, Ph.D. ’25; and Leqi Tian ’24 are co-first authors on this work. Ryan Chaffee, a doctoral student in the field of genetics, genomics and development and Benjamin Haller, a research associate in computational biology, as well as Jackson Champer of Peking University, also contributed.

Funding for the research came from the National Institutes of Health, the National Science Foundation, the Center for Life Sciences and the National Natural Science Foundation of China.

IMAGE CREDIT: Cierra Martin for Crop Trust.