Gene editing races to stay ahead of crop disease

From disease-resistant hybrids to spray-on RNA, new tools could help breeders respond faster, but no single technology can solve every crop challenge.

Depending on the specific tools and methods, the term “genetic modification” has created new opportunities in the lab and in the field, while also fuelling anxiety about advancing plant breeding beyond agriculture.

As each new gene-altering tool or process emerges, science identifies pathways to advance the research pipeline and find answers to everything from environmental stresses to pest resistance. Weed biotypes, insects, and disease pathogens adapt by developing resistance, a complex process despite innovations used to develop new hybrids, varieties, and chemical products.

Gene modification, in the broadest terms, has advanced far beyond selective breeding. Transgenics arrived in the 1990s with RNAi (RNA interference) and CRISPR (clustered regularly interspaced short palindromic repeats) technologies developed in the mid-2000s. Since then, RNAi has helped improve resistance to corn rootworm. At the same time, CRISPR has established resistance to powdery mildew in Chinese wheat and Indian rice varieties that can withstand water scarcity and salinity stress.

WHERE IS THIS LEADING?

A Farm Progress story published last April cited the use of gene editing to speed the development of disease resistance, citing sources with Corteva Agriscience. If current work goes well, a company representative said corn growers in the U.S. could see disease-resistant hybrids as standard on their farms in the early 2030s. That’s a relatively short span given the enormous strides science has made in less than a decade.

Gene editing has been likened to “correcting a spelling mistake” within DNA strands, and although it’s more complicated, its potential to solve many of agriculture’s pest challenges is undeniable. Where transgenics introduced genetic material from one species to another and created resistance to specific herbicides and insect species, gene editing allows for quicker identification and targeting of genes within the plant that can deliver beneficial attributes like disease resistance.

“Old-school transgenic (GMO) technology meant that introducing a new trait took a decade and cost millions in regulatory approvals,” says Dr. Rajagopal Subramanian, a scientist with Agriculture and Agri-Food Canada (AAFC).

“It was a high-stakes, ‘one-and-done’ bet, and if a fungus or virus evolved past that defence, breeders were back to square one.”

In principle, CRISPR is fully programmable. When a pathogen evolves and overcomes a crop’s resistance, scientists can redesign what are known as “guide RNAs” to activate on alternate pathways or splice a backup gene directly into a top-performing commercial hybrid or variety. There’s no need to start over.

“In effect, it turns plant breeding into something like a software update system (on a computer), letting us stay a step ahead in the evolutionary arms race against disease,” says Subramanian.

ONE STEP FORWARD …

Although the technology presents opportunities now and into the future that were not considered possible 20 or 30 years ago, barriers remain to advancing certain crops, specifically wheat. As a hexaploid, wheat carries three related genomes with three or more copies of any given gene. As with the software analogy, a “patch” is often installed across all homoeologous copies to have a phenotypic response. That means knocking out or editing one copy may be masked by the redundant features in the others. In the end, notes Subramanian, updating a genome as complex as wheat requires genome-aware engineering instead of a simple “find-and-replace” process.

It also means corn and soybeans offer some of the more active near-term targets; soybeans because of their record for “knocking out the weakness” type of edits instead of adding new resistance gene types. Both crops also have single- or low-copy susceptibility versus the hexaploid genome found in wheat.

Another factor that complicates establishing disease resistance is the different types of pathogens. Bacteria, viruses, fungi, and oomycetes are four causal agents of plant diseases, so there is no “one-size-fits-all” fix.

“One of the most promising, and most actively-explored – directions in plant immune engineering is targeting conserved pathway ‘hubs’,” adds Subramanian. “Theoretically, that will give you multi-pathogen resistance without having to do pathogen-by-pathogen edits.”

The challenge then is to convert “theoretical” into “practically consistent.”

STILL NO SILVER BULLET

Despite the scientific community’s insistence that no single quick-and-easy cure exists for every emerging crop stress, weed species, or insect infestation, gene editing remains part of a larger research vision. It’s a recent development in a broader innovation toolkit that includes conventional breeding, predictive analytics, doubled haploids, genomics, data science, and, where still appropriate, transgenics.

“Gene editing can help breeders achieve specific performance goals, but it doesn’t operate in isolation, and it’s not a universal replacement for other tools,” says Cory Christensen, corn pipeline development lead with Corteva Agriscience. “When we refer to gene editing or genome editing in this context, we’re talking about targeted changes made within a crop’s own DNA – without introducing genetic material from another species.”

Traits such as disease resistance, yield stability, and plant composition are well-suited to gene editing, while transgenic approaches remain important for specific applications, including select insect-control traits. Multi-disease resistance is likely to be among the first applications to be commercialized by agribusiness stakeholders. Gene editing can be an important tool for discovering and developing solutions that improve crop performance, resilience, or quality.

The ability to work with dozens of genes – as stated in the Farm Progress story – is a significant advantage, adds Christensen, particularly using multiple native resistance genes in a defined location in the genome.

Although breeders can move resistance genes through repeated crossing and selection, that process becomes increasingly difficult and time-consuming as the number of genes increases. Gene editing can simplify that delivery and make it easier to combine multiple sources of resistance.

“Our first-generation concept is designed to deliver resistance to northern leaf blight, gray leaf spot, southern rust, and anthracnose stalk rot,” says Christensen.

“Including more than one resistance gene for key diseases can improve the breadth of protection and support durability. In time, we intend to keep expanding the disease targets we can address through seed-based genetic resistance.”

A first-generation launch of gene-edited, disease-resistant hybrids or varieties is pending product testing and regulatory authorizations.

ANOTHER GAME-CHANGER

Beyond gene editing, researchers and agribusinesses are working to bring “spray-on” molecular technologies to growers. Spray-induced gene silencing (SIGS) is in its early stages, yet the technology represents a huge leap forward in crop protection. According to Subramanian, the products are applied topically and degrade naturally, delivering the precision of gene editing without permanently altering the crop’s DNA. It uses double-stranded RNA (dsRNA) to silence specific pathogen genes through RNAi.

“That offers a much faster, smoother regulatory path,” he says, adding that they’re highly programmable. “If a sudden new disease outbreak occurs, scientists can rapidly redesign the spray’s active molecules to target the new threat within weeks, giving growers an agile, rapid-response tool to combat emerging crises.”

Peptide binders are another visionary technology. They are small, engineered amino acid chains designed to bind to and disable pathogen proteins. •