UC Davis awarded grant for Oral CRISPR treatment

October 4, 2019 -- UC Davis researchers have just been awarded $1.5 million from the National Institutes of Health (NIH) to start work of a novel approach to deliver CRISPR genome-editing machinery to gut cells in a way that will fix genes responsible for a rare form of familial cancer. The research team hopes that this work will lead to new treatments for diseases of the gut.

The research team aims to demonstrate that CRISPR, a technology that allows alteration of DNA sequences to modify gene function, can be successfully packaged and delivered to target cells in a living animal. The target of this CRISPR model is the hepatitis E virus, which they hope to protect against by editing the APC gene to suppress tumor growth.

"The question is how to deliver CRISPR into target cells in cancer or precancer then edit the gene," said Kit S. Lam, distinguished professor and chair of the Department of Biochemistry and Molecular Medicine in the School of Medicine. "You can do this relatively easily in cell culture - getting it to living cells. But to deliver CRISPR to disease tissues or organs in a living animal is a big challenge. That is our goal."

The multidisciplinary research involves designing a CRISPR gene-editing system which is delivered using combinatorial chemistry and nanotechnology. The non-infectious hepatitis E virus will be created in the laboratory, and then be encapsulated for oral delivery in mice models.

"Using protein engineering and a state-of-the-art cryo-electron microscope, we have optimized the hepatitis E viral capsule as a unique and effective nanodelivery carrier," said R. Holland Cheng, professor of Molecular and Cellular Biology in the College of Biological Sciences. "Through our structure-guided design and the evolutional advantage of a water-borne agent, our viral vector can pass through the harsh environment of the stomach and deliver the loaded gene editors to targeted cells in the gut."

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