Pairing CRISPR with a smartphone camera, this COVID-19 test finds results in 30 minutes

CRISPR-Cas9
The team consists of scientists from the University of California, San Francisco, UC Berkeley, and the Gladstone Institutes—including a collaboration with Jennifer Doudna, winner of the 2020 Nobel Prize for her co-discovery of CRISPR genome editing. (Ernesto del Aguila III, NHGRI)(Ernesto del Aguila III, National Human Genome Research Institute, NIH)

Researchers in California aim to develop a new CRISPR-based test for COVID-19 that can be read anytime, anywhere by turning a basic smartphone camera into a microscope capable of detecting the coronavirus’ genetic material.

The team consists of scientists from the University of California, San Francisco, UC Berkeley, and the Gladstone Institutes—including a collaboration with Jennifer Doudna, president of the Innovative Genomics Institute, and winner of the 2020 Nobel Prize in Chemistry for co-discovering CRISPR-Cas genome editing, the technology that underpins the test.

"It has been an urgent task for the scientific community to not only increase testing but also to provide new testing options," said Melanie Ott, director of the Gladstone Institute of Virology and one of the leaders of a study evaluating the test, published in Cell. "The assay we developed could provide rapid, low-cost testing to help control the spread of COVID-19."

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The smartphone diagnostic aims to provide a positive or negative result in less than 30 minutes, as well as gauge the amounts of SARS-CoV-2 virus present in a nasal swab sample.

"When coupled with repeated testing, measuring viral load could help determine whether an infection is increasing or decreasing," said UC Berkeley bioengineer Daniel Fletcher, a Chan Zuckerberg Biohub investigator. "Monitoring the course of a patient's infection could help health care professionals estimate the stage of infection and predict, in real time, how long is likely needed for recovery."

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Most current molecular tests for COVID-19 are based on PCR—a method that requires the virus’ RNA to be converted into DNA before the diagnostics can work. It also needs to amplify that DNA, by repeatedly making copies to capture a detectable signal, which calls for specialized chemical reagents and laboratory equipment.

The diagnostic test requires a cell phone
camera and a small darkened box.
(Photo courtesy of Daniel Fletcher)

Alternatively, the researchers’ approach uses CRISPR proteins designed to hunt directly for the virus’ RNA, skipping the conversion and amplification steps.

"One reason we're excited about CRISPR-based diagnostics is the potential for quick, accurate results at the point of need," said Doudna, whose CRISPR-focused company Mammoth Biosciences was tapped earlier this year by GlaxoSmithKline to develop an over-the-counter COVID-19 test.

"This is especially helpful in places with limited access to testing, or when frequent, rapid testing is needed. It could eliminate a lot of the bottlenecks we've seen with COVID-19," she said.

The new test uses a Cas13 protein tagged with a molecule that glows once it’s cut, as part of the genetic-snipping that occurs when it matches up with a specific piece of RNA. When more of the virus’ genome is present, more cuts occur—creating a brighter glow that can be picked up by a smartphone camera used with a darkened box.

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The team of researchers had originally been pursuing the quick testing method as a potential diagnostic for HIV, but pivoted to the coronavirus as the pandemic began to spread this year.

"We knew the assay we were developing would be a logical fit to help the crisis by allowing rapid testing with minimal resources," co-first author Parinaz Fozouni, a UCSF graduate student working in Ott's lab at Gladstone. "Instead of the well-known CRISPR protein called Cas9, which recognizes and cleaves DNA, we used Cas13, which cleaves RNA."

The study also found that samples with high concentrations of the virus produced a signal much faster, with positive results for someone who potentially more likely to be contagious delivered in under 5 minutes.

"Recent models of SARS-CoV-2 suggest that frequent testing with a fast turnaround time is what we need to overcome the current pandemic," said Ott. "We hope that with increased testing, we can avoid lockdowns and protect the most vulnerable populations."

In addition to being widely available and cheaper compared to lab equipment, smartphones could also make use of their GPS and digital connectivity to help track the spread of infections in various regions.

"We hope to develop our test into a device that could instantly upload results into cloud-based systems while maintaining patient privacy, which would be important for contact tracing and epidemiologic studies," Ott said. "This type of smartphone-based diagnostic test could play a crucial role in controlling the current and future pandemics."