CRISPR Breakthrough Could Help Scientists More Quickly Combat Pathogens

A new strategy to edit the genome of filamentous fungi could have implications for scientists’ ability to use tools like CRISPR to prevent or contain infectious diseases in the future.

A team of investigators from Tokyo University of Science, Meiji University, and the Tokyo University of Agriculture and Technology unveiled their new genome editing strategies last month in the journal Scientific Reports.

The team used CRISPR/Cas9 to devise a new system for introducing a single gene into the rice blast fungus Pyricularia (Magnaporthe) oryzae. The new method has the potential to make CRISPR/Cas9 gene editing considerably quicker. The team also developed several strategies to increase the efficiency of targeted gene disruption.

Although the findings have a most immediate impact on agriculture—rice blast fungus can devastate rice crops—the research will likely also have impacts on human pathogens, both in the short term and long term, said Takayuki Arazoe, PhD, an assistant professor of applied biological science at the Tokyo University of Science.

“Because there are some coincidences between the genomic characteristics of plant and human pathogens, a part of these strategies may be also able to apply for human pathogens including pathogenic protozoa,” Arazoe told Contagion^® referencing malaria as 1 example of a human pathogen that might be affected by this research.

In Scientific Reports, Arazoe and colleagues explain that their system helps to offset a main limitation of the CRISPR/Cas9 system—in order to make DNA binding effective, scientists must first develop a pattern called a protospacer-adjacent motif (PAM). The new research suggests PAMs might not be necessary after all.

“In this study, we developed a novel genome editing strategy via single crossover-mediated HR in the model filamentous fungus Pyricularia( Magnaporthe) oryzae,” investigators wrote. “This method includes the CRISPR/Cas9 system and a donor vector harboring a single homology arm with point mutations at the CRISPR/Cas9 cleavage site.”

The most immediate impact of the new research is that it will make it easier for investigators to leverage genome editing to understand and eventually fight destructive pathogens.

“First, the development of novel genome editing technologies including our exploited strategy can speed up molecular biological research, such as functional gene (genome) analysis, to understand about how a pathogen has specific properties for infection and pathogenicity,” Arazoe said.

Such advances could open up an entirely new range of strategies by which to combat pathogens. For instance, scientists might be able to modify the genomes of pathogens in order to make them more susceptible to herbicides or medications, or to make them unable to withstand natural foes.

Eventually, though, Arazoe said, such techniques have the potential to go much further, perhaps to the point of rendering the pathogens entirely ineffective.

“Our final goal is to find out the targets to simultaneously control the pathogen evolution and infection,” he said.

That goal, however, is far off at the moment. Arazoe said more research will be needed to ensure investigators engaged in pathogen genomic engineering have adequate control over the pathogens.