CRISPR comes of age years ahead of schedule with first diagnostic authorization

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FDA’s authorization of a CRISPR-based diagnostic for COVID-19 from Sherlock Biosciences is another step in the right direction for COVID-19 diagnostics, but it’s a much bigger win for the CRISPR technology.

It represents the first time a CRISPR-based product has been authorized for use in healthcare, and it comes years before anyone was expecting it.

“This authorization has propelled CRISPR into healthcare,” said Rahul Dhanda, CEO of Sherlock Biosciences Inc., the diagnostics company tied to CRISPR IP from the Broad Institute of MIT and Harvard. “Most people think of CRISPR as a gene editing tool that has this amazing therapeutic potential, and we’re honored and thrilled that Sherlock is the first to really get something authorized for use with patients. That to us is almost as exciting as the fact that it’s being applied to target COVID-19.”

FDA granted emergency use authorization to the CRISPR SARS-CoV-2 test kit that uses the SHERLOCK (Specific High Sensitivity Enzymatic Reporting UnLOCKing) platform to detect viral RNA using Cas13. The test takes about an hour to run on standard equipment found in any CLIA lab and has a sensitivity and specificity of 100%.

According to the EUA, the test has a limit of detection of 6.7 copies/μL, making it one of the least sensitive among the authorized tests. Diagnostic tests for COVID-19 with EUA from FDA have a range of sensitivities, and it isn’t yet clear what limit of detection is sufficient (see “Pushing the Limits of Detection”).

Although Sherlock announced a collaboration with Cepheid Inc. in February to develop a CRISPR-based test to run on the partners’ cartridge-based GeneXpert system, Sherlock opted for a test kit that can run through centralized labs for its first iteration.

“What this has done is accelerate many aspects of our technology that will give us an edge.”

Rahul Dhanda, Sherlock

“We felt right now, the issue was getting more capacity. We wanted this to fit into high-throughput labs that can do higher volume testing. We feel that the need for decentralized testing will be more acute in the next wave, and we’re thinking about how to address that,” he said.

The company is exploring cartridge-based systems for the next wave of infections, and it’s looking to a new CRISPR-based technology dubbed INSPECTR (INternal Splint-Pairing Expressing Cassette Translation Reaction) for home-based testing for further down the line.

According to Sherlock Chief Technology Officer William Blake, INSPECTR is an instrument-free synthetic biology platform that can detect the presence of nucleic acids without requiring the amplification step needed for PCR and the existing SHERLOCK test. “The technology signals the presence of a nucleic acid by producing something -- an enzyme that gives off a luminescent signal or a color change or a peptide antigen that a flow test that exists today could detect,” he said.

A group of academic scientists including Feng Zhang -- Sherlock’s scientific founder and a CRISPR pioneer -- shared a separate diagnostic method this week based on SHERLOCK dubbed STOP (SHERLOCK Testing in One Pot) Covid, which they describe as a step towards at-home testing. It requires a steady temperature control for 60 minutes, but was able to read out using a lateral flow strip without a fluorescent reader. The test’s limit of detection was 100 copies of viral genome in saliva or nasopharyngeal swabs per reaction.

Dhanda told BioCentury Sherlock was not affiliated with the work, but because it used the SHERLOCK technology and the company has a license to the Broad Institute’s CRISPR IP estate for diagnostic applications, it would be brought into Sherlock if anything develops from it.

The pandemic has accelerated development and validation of technologies spanning nucleic acid vaccines to remote patient monitoring, and CRISPR is no exception.

For Sherlock, the pandemic cut at least two years off its development timeline and enabled the diagnostic technology to leapfrog CRISPR-based therapeutics in clinical development. It’s because of the novel coronavirus that Sherlock and other diagnostics companies, rather than drugmakers, will have the first opportunity to demonstrate the transformative potential of the gene editing technology (see “CRISPR-Based Diagnostics are Poised to Make an Early Debut“).

“This company formed a year ago. We were planning for a product in 2022 or 2023, and so many things had to go right for that to happen. Seeing this small company of 20 people drive forward, during a stay-at-home order in our state, was one of the most amazing things I’ve seen in my career,” said Dhanda.

It’s been all hands on deck for the COVID-19 projects at Sherlock, but the technology advances that have been achieved for COVID will translate to other indications.

“What this has done is accelerate many aspects of our technology that will give us an edge in achieving those goals and developing those applications when we get back to normal. What we’re learning are things translatable across the platform, but for the foreseeable future, we feel very compelled to focus on COVID-19,” said Dhanda.

At least two other companies are developing CRISPR-based diagnostics for the pandemic. Mammoth Biosciences, which was formed around the CRISPR technology developed by University of California Berkeley professor Jennifer Doudna, hasn’t given a timeline for its first test. Caspr Biotech is using a Cas12-based technology to diagnose the infection, and said in March that a test could be available in the coming months (see “COVID-19 Crisis Spurs Innovation”).

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