MU researcher receives $3 million grant to use gene editing for investigating the building blocks of disease

In a new study funded by a $3 million grant from the National Institutes of Health (NIH), University of Missouri researcher Kiho Lee, an associate professor in the College of Agriculture, Food and Natural Resources, will use gene editing to investigate the building blocks of disease. His ultimate goal -; to discover clinically significant explanations for human diseases like Alzheimer's, cancer and infertility, while working on solutions to global food insecurity.

Common diseases, such as Alzheimer's, are widespread in humans, plaguing an estimated 11% or 6.7 million Americans over age 65, according to The Alzheimer's Association. Some Alzheimer's diseases, specifically early onset cases, are highly linked to a person's genetic background, of which gene editing could be a future solution. This dual-purpose grant will encourage scientific innovation not only in the biomedical realm, which would focus on human disease, but also in agriculture, where Lee is hopeful this research will improve pig welfare as well as increase food production for farmers.

Working toward this outcome, Lee and his team will evaluate the efficacy and safety of genome editing technology -; known as the CRISPR/Cas system -; to improve the gene-testing process and design approaches that help researchers make the most of a targeted genome editing event. The study objective involves investigating three specific aims:

• Develop a method for the global detection of unintended outcomes from gene editing in genetically engineered pigs.
• Design a method for ensuring the integrity of the genome when gene editing.
• Establish a strategy for rapidly phenotyping genetically engineered pigs in utero and modifying the genome of wild-type adult pigs to ensure favorable traits for agriculture and biomedicine.

"Ultimately, the goal is to generate founder pigs that have fewer unintended modifications, which we call 'off-targeting events,'" Lee said. "This way, the founder animals -; those with modified genomes -; would present the phenotype or trait that we intend to generate, making the whole process more effective."

This study will help scientists refine the mechanism of gene editing to streamline what traits the animals will exhibit. Because breeding genetically engineered pigs often takes a significant time commitment, this is an important component to this study.

Obviously, this research has both biomedical and agricultural implications. As such, one of the phenotypes we are interested in is growth because we want our pigs to grow bigger in a shorter period of time, which would help maintain food sustainability worldwide. Making these models helps patients who are suffering from these diseases. And, although my passion is directed more toward biomedical research, when I sit down and think about it, the agricultural component has a deep impact. For example, population growth and the amount of food we need to secure in the face of climate change means we need these technologies to ensure we can respond to uncertainties and still feed everybody. Hopefully, my work will have an impact on both."

Kiho Lee, Associate Professor, College of Agriculture, Food and Natural Resources, University of Missouri

A USDA-ARS scientist, Bethany Redel, will bring her expertise to this research, which highlights not only the existing collaboration between the University of Missouri and USDA-ARS but also an ongoing commitment to finding solutions that support the future of agriculture. This funding was awarded as part of the Dual Purpose with Dual Benefit program, which is a collaboration between the NIH and the USDA.