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ChristianaCare works with MIT, Stanford to advance COVID-19 testing

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Shirin Modarai, Ph.D., research scientist, Sambee Kanda, MS, research assistant, Eric Kmiec, Ph.D., director | PHOTO COURTESY OF CHRISTIANACARE

CHRISTIANA – Eric Kmiec has studied molecular medicine and gene editing for 30 years, but he’s rarely seen a time when the fruits of research are so readily at hand.

As director of the Gene Editing Institute of the Helen F. Graham Cancer Center & Research Institute at ChristianaCare, Kmiec has been leading the New Castle County-based health system’s effort to study patients’ responses to the COVID-19 virus.

The Gene Editing Institute is internationally known for its work with CRISPR, an emerging technology that allows scientists to examine genetic defects and treat them at a level not seen in prior decades. Calling it “the genetic spell checker of human disease,” Kmiec explained that CRISPR is a bacteria’s genetic defense against viruses, which scientists have learned to use as a tool.

“It helps us correct inherited diseases like cystic fibrosis or sickle cell disease, but it will also help us to disable genes that are malfunctioning in cancer,” Kmiec said, noting that ChristianaCare’s work to date is aimed at lung and pancreatic cancer.

Studying gene panels with Stanford, Cal, and biotechs

In mid-May, the Gene Editing Institute was contacted by a consortium of researchers at Stanford University, the University of California, Berkeley and several biotechnology companies to join an effort that is seeking to determine which genes are responding to a COVID-19 infection.

“That’s really the problem in the country right now. Some people who get infected remain asymptomatic while others have a variety of levels of response,” he said.

Kmiec said that researchers will study gene panels obtained from COVID-19 patients, likely through saliva or blood samples, to seek out the genes that may be influencing a patient’s response to the virus. Once they can determine the genes, scientists may be able to identify easier to discern factors related to those genes, such as genetic ancestry, inherited diseases, and socioeconomic factors.

If the work is successful, Kmiec said CRISPR tests may one day be able to tell hospitals how an individual patient may fare with the virus early on in their diagnosis, potentially leading to better allocation of resources and treatment of patients.

Kmiec said that because the study will likely require a year of testing of patients, it is unlikely to be used in response to the COVID-19 pandemic. Because COVID-19 is among the SARS family of coronaviruses, which already saw a prior pandemic in 2002, epidemiologists believe there will likely be more such pandemics in the future where the CRISPR science could be applied though.

“We’re cautiously optimistic that we’ll be able to come up with something in the next year or so that will help us understand what genes are accounting for that for the response,” Kmiec said. “It’s not easy, but I think CRISPR has got everybody excited because it allows us to attempt to do that.”

Eric Kmiec, Ph.D., director, Amanda Hewes, MS, research associate, Brett Sansbury, Ph.D., group leader discovery | PHOTO COURTESY OF CHRISTIANACARE

Working with MIT on a diagnostic test

While Kmiec’s team works on the gene panel study, it is also aiding the Massachusetts Institute of Technology to refine a CRISPR-based diagnostic test for COVID-19 that its researchers helped develop.

Kmiec said that his team has worked with MIT previously and when he heard that the university was developing its own test using CRISPR, he called them a few weeks ago to see if the Gene Editing Institute could help.

“They sent us samples of their test overnight,” he recalled.

Kmiec explained that the so-called Sherlock test – developed by MIT, Harvard University, Ragon Institute, and the Howard Hughes Medical Institute – uses CRISPR to search for the COVID-19 virus’s RNA and binds to it if found. The science comes with huge advantages compared to the more common nasal swab polymerase chain reaction (PCR) test: time and money.

Labs need more expensive thermocycler equipment to run a PCR test and the tests themselves cost upward of $200 each. In comparison, no expensive equipment is needed for the Sherlock test, and the tests themselves cost about $6 each, Kmiec said.

“It will save the state and health systems an ungodly amount of money if it proves to be as effective,” he added.

The test can also return results in a matter of hours, which would help in the pandemic response of rural or impoverished communities that may not have access to the expensive PCR equipment, and are forced to wait days for test results from farther afield, Kmiec said.

To help the effort, Kmiec’s team is working to improve the sensitivity of the Sherlock test as well as fine tune it to the COVID-19 strain that is found in Delaware. Each region seems to have slight variations in the viral type, and Kmiec explained that the CRISPR test will have to be tailored to a region and its population. The Gene Editing Institute has been working in partnership on its research with Nemours/Alfred I. duPont Hospital for Children, which has the ability to verify the results found by Kmiec’s team.

“We’re hoping that this test can really become sort of the standard of care because frankly, it could be used in places where they don’t have the opportunity to have major instrumentation to run the PCR test,” he said.

By Jacob Owens

[email protected]

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