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Nanotech Crispr Delivery in Development

Editing a DNA strand

Editing a DNA strand illustration (XVIVO, NIH/NCATS)

2 Oct. 2019. Researchers in biochemistry and structural biology are designing a technique using nanoscale particles to safely deliver edited genes as a cancer treatment. The research now underway at University of California in Davis is funded by a two-year, $1.5 million grant from National Center for Advancing Translational Sciences, or NCATS, part of National Institutes of Health.

A team led by UC Davis biochemistry professor and cancer researcher Kit Lam and protein biologist R. Holland Cheng are seeking safer and more efficient techniques for delivering edited genes as treatments for cancer and other diseases. The gene-editing technique Crispr — short for clustered, regularly interspaced short palindromic repeats — makes it possible to edit genomes of organisms by harnessing bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA.

While delivering edited genes to cells in lab cultures is feasible, the task is more difficult in living mammals, including humans. Lam, Cheng, and colleagues propose genetically engineering a strain of hepatitis virus to carry the edited genes as nanoscale delivery vehicles into cells. The engineered hepatitis E virus, a product of Cheng’s lab, would be small enough to be formulated into an oral drug, yet still be non-infectious to the recipient. The surface of these nanoparticles will have binding molecules that target specific cells for the particles’ delivery.

To prove the concept, the researchers plan to test the nanoparticles in lab mice induced with familial adenomatous polyposis, an inherited condition and a high-risk factor for colon cancer. For this application, the engineered hepatitis E virus is an ideal carrier, since the virus can withstand stomach acids and survive the journey to the intestines.  The viral carriers will be fed to the mice, and contain edited adenomatous polyposis coli or APC genes, to correct mutations that allow tumors in the colon to occur.

“Through our structure-guided design and the evolutional advantage of a water-borne agent,” says Cheng in a university statement, “our viral vector can pass through the harsh environment of the stomach and deliver the loaded gene editors to targeted cells in the gut.”

Financing for this research come from NIH’s Common Fund, a centrally controlled source devoted to studies addressing high-priority needs that cut across the agency’s institute boundaries. One of the Common Fund’s programs supports research on somatic cell genome editing. Somatic cells are outside the reproductive process, thus allowing gene edits that will not be passed on to future generations. The UC Davis award is part of a recent addition of $89 million to advance genome editing.

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