Disease resistant crops through disabling susceptibility genes

Plant breeding can have various objectives: higher yields, better quality, improved salt or drought tolerance, or enhanced resistance to diseases and pests. The Plant Breeding research group at WUR focuses on strengthening plant resilience against bacteria, fungi, viruses, and insects that transmit these pathogens, explains Henk Schouten, senior researcher in plant breeding. “The more resilient a crop is, the fewer crop protection products growers need to use. Our research focuses on developing durable resistance. It’s relatively easy to introduce resistance into a variety through traditional breeding, but pathogens can adapt within a few years—rendering that resistance ineffective.”

One way to create durable resistance is by disabling susceptibility genes, Schouten explains. “Pathogens such as viruses use plant genes to reproduce and infect the plant. When we modify or disable these susceptibility genes through targeted mutations, the pathogen can no longer reproduce—and the plant becomes resistant. At WUR, the group led by Professor Yuling Bai, Chair of Plant Breeding, has played a major role in discovering and disabling these genes. We are now revealing the underlying mechanisms and genes in more detail, so we can help breeders introduce resistance more effectively.”

A key technology for disabling susceptibility genes is CRISPR-Cas. Schouten: “CRISPR-Cas uses an enzyme that works like a pair of scissors to make changes in DNA precisely at predefined positions. Such a targeted mutation in a susceptibility gene can make the plant less vulnerable to a pathogen. WUR Professor of Microbiology John van der Oost has been one of the pioneers of CRISPR-Cas technology. Our group is now collaborating with Microbiology on the further development of CRISPR-Cas—specifically ThermoCas9. The Microbiology team is improving the ThermoCas9 enzyme, and we test it in plants. Once the technology is ready, we’ll work with companies to explore new applications and innovations.”

In addition to disabling susceptibility genes, WUR also focuses on introducing natural resistance genes from wild plants. The method used is called cisgenesis, Schouten says. “Put simply, it means transferring resistance genes from wild plants into cultivated varieties that are crossable with those wild relatives. Using genetic modification (GM) to do this speeds up the process dramatically compared to traditional breeding for slow breeding crops such as fruit trees. Around the turn of the century, I started working on this in Wageningen to introduce resistance against apple scab. However, because cisgenesis falls under European GMO legislation, it has not been permitted for marketable varieties. The same applies to CRISPR-Cas and related techniques such as ThermoCas9.”

According to Schouten, this is now about to change. “The European Parliament has voted to ease market access of both cisgenic crops and crops with targeted CRISPR-Cas mutations in the EU—mainly because developing disease-resistant varieties is of great societal importance. I think this is a wonderful decision and a real milestone. Being able to use these technologies for market products is a dream come true. It gives new momentum to our research on cisgenesis—not only for scab-resistant apples, but also for potatoes resistant to Phytophthora infestans. We’re preparing a field trial in Lelystad with cisgenic potatoes.”

Because CRISPR-Cas is patented in the United States, using the technology commercially is relatively expensive. However, Schouten expects that WUR’s ThermoCas9 variant will differ enough to allow for independent patents. “We want to make CRISPR-ThermoCas9 freely available to developing countries for non-commercial applications. It’s very important to us that people with low incomes also benefit from our innovations. For commercial use, we will offer the technology for a relatively low fee—because only in that way our research can have broad impact.”