Tag Archives: Sherlock Biosciences

The Broad Institute gives us another reason to love CRISPR

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More and more, this resembles a public relations campaign. First, CRISPR (clustered regularly interspersed short palindromic repeats) gene editing is going to be helpful with COVID-19 and now it can help us to deal with conservation issues. (See my May 26, 2020 posting about the latest CRISPR doings as of May 7, 2020; included is a brief description of the patent dispute between Broad Institute and UC Berkeley and musings about a public relations campaign.)

A May 21, 2020 news item on ScienceDaily announces how CRISPR could be useful for conservation,

The gene-editing technology CRISPR has been used for a variety of agricultural and public health purposes — from growing disease-resistant crops to, more recently, a diagnostic test for the virus that causes COVID-19. Now a study involving fish that look nearly identical to the endangered Delta smelt finds that CRISPR can be a conservation and resource management tool, as well. The researchers think its ability to rapidly detect and differentiate among species could revolutionize environmental monitoring.

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Caption: Longfin smelt can be difficult to differentiate from endangered Delta smelt. Here, a longfin smelt is swabbed for genetic identification through a CRISPR tool called SHERLOCK. Credit: Alisha Goodbla/UC Davis

A May 21, 2020 University of California at Davis (UC Davis) news release (also on EurekAlert) by Kat Kerlin, which originated the news item, provides more detail (Note: A link has been removed),

The study, published in the journal Molecular Ecology Resources, was led by scientists at the University of California, Davis, and the California Department of Water Resources in collaboration with MIT Broad Institute [emphasis mine].

As a proof of concept, it found that the CRISPR-based detection platform SHERLOCK (Specific High-sensitivity Enzymatic Reporter Unlocking) [emphasis mine] was able to genetically distinguish threatened fish species from similar-looking nonnative species in nearly real time, with no need to extract DNA.

“CRISPR can do a lot more than edit genomes,” said co-author Andrea Schreier, an adjunct assistant professor in the UC Davis animal science department. “It can be used for some really cool ecological applications, and we’re just now exploring that.”

WHEN GETTING IT WRONG IS A BIG DEAL

The scientists focused on three fish species of management concern in the San Francisco Estuary: the U.S. threatened and California endangered Delta smelt, the California threatened longfin smelt and the nonnative wakasagi. These three species are notoriously difficult to visually identify, particularly in their younger stages.

Hundreds of thousands of Delta smelt once lived in the Sacramento-San Joaquin Delta before the population crashed in the 1980s. Only a few thousand are estimated to remain in the wild.

“When you’re trying to identify an endangered species, getting it wrong is a big deal,” said lead author Melinda Baerwald, a project scientist at UC Davis at the time the study was conceived and currently an environmental program manager with California Department of Water Resources.

For example, state and federal water pumping projects have to reduce water exports if enough endangered species, like Delta smelt or winter-run chinook salmon, get sucked into the pumps. Rapid identification makes real-time decision making about water operations feasible.

FROM HOURS TO MINUTES

Typically to accurately identify the species, researchers rub a swab over the fish to collect a mucus sample or take a fin clip for a tissue sample. Then they drive or ship it to a lab for a genetic identification test and await the results. Not counting travel time, that can take, at best, about four hours.

SHERLOCK shortens this process from hours to minutes. Researchers can identify the species within about 20 minutes, at remote locations, noninvasively, with no specialized lab equipment. Instead, they use either a handheld fluorescence reader or a flow strip that works much like a pregnancy test — a band on the strip shows if the target species is present.

“Anyone working anywhere could use this tool to quickly come up with a species identification,” Schreier said.

OTHER CRYPTIC CRITTERS

While the three fish species were the only animals tested for this study, the researchers expect the method could be used for other species, though more research is needed to confirm. If so, this sort of onsite, real-time capability may be useful for confirming species at crime scenes, in the animal trade at border crossings, for monitoring poaching, and for other animal and human health applications.

“There are a lot of cryptic species we can’t accurately identify with our naked eye,” Baerwald said. “Our partners at MIT are really interested in pathogen detection for humans. We’re interested in pathogen detection for animals as well as using the tool for other conservation issues.”

Here’s a link to and a citation for the paper,

Rapid and accurate species identification for ecological studies and monitoring using CRISPR‐based SHERLOCK by Melinda R. Baerwald, Alisha M. Goodbla, Raman P. Nagarajan, Jonathan S. Gootenberg, Omar O. Abudayyeh, Feng Zhang, Andrea D. Schreier. Molecular Ecology Resources https://doi.org/10.1111/1755-0998.13186 First published: 12 May 2020

This paper is behind a paywall.

The business of CRISPR

SHERLOCK™, is a trademark for what Sherlock Biosciences calls one of its engineering biology platforms. From the Sherlock Biosciences Technology webpage,

What is SHERLOCK™?

SHERLOCK is an evolution of CRISPR technology, which others use to make precise edits in genetic code. SHERLOCK can detect the unique genetic fingerprints of virtually any DNA or RNA sequence in any organism or pathogen. Developed by our founders and licensed exclusively from the Broad Institute, SHERLOCK is a method for single molecule detection of nucleic acid targets and stands for Specific High Sensitivity Enzymatic Reporter unLOCKing. It works by amplifying genetic sequences and programming a CRISPR molecule to detect the presence of a specific genetic signature in a sample, which can also be quantified. When it finds those signatures, the CRISPR enzyme is activated and releases a robust signal. This signal can be adapted to work on a simple paper strip test, in laboratory equipment, or to provide an electrochemical readout that can be read with a mobile phone.

However, things get a little more confusing when you look at the Broad Institute’s Developing Diagnostics and Treatments webpage,

Ensuring the SHERLOCK diagnostic platform is easily accessible, especially in the developing world, where the need for inexpensive, reliable, field-based diagnostics is the most urgent

SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) is a CRISPR-based diagnostic tool that is rapid, inexpensive, and highly sensitive, with the potential to have a transformative effect on research and global public health. The SHERLOCK platform can detect viruses, bacteria, or other targets in clinical samples such as urine or blood, and reveal results on a paper strip — without the need for extensive specialized equipment. This technology could potentially be used to aid the response to infectious disease outbreaks, monitor antibiotic resistance, detect cancer, and more. SHERLOCK tools are freely available [emphasis mine] for academic research worldwide, and the Broad Institute’s licensing framework [emphasis mine] ensures that the SHERLOCK diagnostic platform is easily accessible in the developing world, where inexpensive, reliable, field-based diagnostics are urgently needed.

Here’s what I suspect. as stated, the Broad Institute has free SHERLOCK licenses for academic institutions and not-for-profit organizations but Sherlock Biosciences, a Broad Institute spinoff company, is for-profit and has trademarked SHERLOCK for commercial purposes.

Final thoughts

This looks like a relatively subtle campaign to influence public perceptions. Genetic modification or genetic engineering as exemplified by the CRISPR gene editing technique is a force for the good of all. It will help us in our hour of need (COVID-19 pandemic) and it can help us save various species and better manage our resources.

This contrasts greatly with the publicity generated by the CRISPR twins situation where a scientist claimed to have successfully edited the germline for twins, Lulu and Nana. This was done despite a voluntary, worldwide moratorium on germline editing of viable embryos. (Search the terms [either here or on a standard search engine] ‘CRISPR twins’, ‘Lulu and Nana’, and/or ‘He Jiankui’ for details about the scandal.

In addition to presenting CRISPR as beneficial in the short term rather than the distant future, this publicity also subtly positions the Broad Institute as CRISPR’s owner.

Or, maybe I’m wrong. Regardless, I’m watching.

US Food and Drug Administration (FDA) gives first authorization for CRISPR (clustered regularly interspersed short palindromic repeats) use in COVID-19 crisis

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Clustered regularly interspersed short palindromic repeats (CRISPR) gene editing has been largely confined to laboratory use or tested in agricultural trials. I believe that is true worldwide excepting the CRISPR twin scandal. (There are numerous postings about the CRISPR twins here including a Nov. 28, 2018 post, a May 17, 2019 post, and a June 20, 2019 post. Update: It was reported (3rd. para.) in December 2019 that He had been sentenced to three years jail time.)

Connie Lin in a May 7, 2020 article for Fast Company reports on this surprising decision by the US Food and Drug Administration (FDA), Note: A link has been removed),

The U.S. Food and Drug Administration has granted Emergency Use Authorization to a COVID-19 test that uses controversial gene-editing technology CRISPR.

This marks the first time CRISPR has been authorized by the FDA, although only for the purpose of detecting the coronavirus, and not for its far more contentious applications. The new test kit, developed by Cambridge, Massachusetts-based Sherlock Biosciences, will be deployed in laboratories certified to carry out high-complexity procedures and is “rapid,” returning results in about an hour as opposed to those that rely on the standard polymerase chain reaction method, which typically requires six hours.

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The announcement was made in the FDA’s Coronavirus (COVID-19) Update: May 7, 2020 Daily Roundup (4th item in the bulleted list), Or, you can read the May 6, 2020 letter (PDF) sent to John Vozella of Sherlock Biosciences by the FDA.

As well, there’s the May 7, 2020 Sherlock BioSciences news release (the most informative of the lot),

Sherlock Biosciences, an Engineering Biology company dedicated to making diagnostic testing better, faster and more affordable, today announced the company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for its Sherlock™ CRISPR SARS-CoV-2 kit for the detection of the virus that causes COVID-19, providing results in approximately one hour.

“While it has only been a little over a year since the launch of Sherlock Biosciences, today we have made history with the very first FDA-authorized use of CRISPR technology, which will be used to rapidly identify the virus that causes COVID-19,” said Rahul Dhanda, co-founder, president and CEO of Sherlock Biosciences. “We are committed to providing this initial wave of testing kits to physicians, laboratory experts and researchers worldwide to enable them to assist frontline workers leading the charge against this pandemic.”

The Sherlock™ CRISPR SARS-CoV-2 test kit is designed for use in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests. Based on the SHERLOCK method, which stands for Specific High-sensitivity Enzymatic Reporter unLOCKing, the kit works by programming a CRISPR molecule to detect the presence of a specific genetic signature – in this case, the genetic signature for SARS-CoV-2 – in a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage (BAL) specimen. When the signature is found, the CRISPR enzyme is activated and releases a detectable signal. In addition to SHERLOCK, the company is also developing its INSPECTR™ platform to create an instrument-free, handheld test – similar to that of an at-home pregnancy test – that utilizes Sherlock Biosciences’ Synthetic Biology platform to provide rapid detection of a genetic match of the SARS-CoV-2 virus.

“When our lab collaborated with Dr. Feng Zhang’s team to develop SHERLOCK, we believed that this CRISPR-based diagnostic method would have a significant impact on global health,” said James J. Collins, co-founder and board member of Sherlock Biosciences and Termeer Professor of Medical Engineering and Science for MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “During what is a major healthcare crisis across the globe, we are heartened that the first FDA-authorized use of CRISPR will aid in the fight against this global COVID-19 pandemic.”

Access to rapid diagnostics is critical for combating this pandemic and is a primary focus for Sherlock Biosciences co-founder and board member, David R. Walt, Ph.D., who co-leads the Mass [Massachusetts] General Brigham Center for COVID Innovation.

“SHERLOCK enables rapid identification of a single alteration in a DNA or RNA sequence in a single molecule,” said Dr. Walt. “That precision, coupled with its capability to be deployed to multiplex over 100 targets or as a simple point-of-care system, will make it a critical addition to the arsenal of rapid diagnostics already being used to detect COVID-19.”

This development is particularly interesting since there was a major intellectual property dispute over CRISPR between the Broad Institute (a Harvard University and Massachusetts Institute of Technology [MIT] joint initiative), and the University of California at Berkeley (UC Berkeley). The Broad Institute mostly won in the first round of the patent fight, as I noted in a March 15, 2017 post but, as far as I’m aware, UC Berkeley is still disputing that decision.

In the period before receiving authorization, it appears that Sherlock Biosciences was doing a little public relations and ‘consciousness raising’ work. Here’s a sample from a May 5, 2020 article by Sharon Begley for STAT (Note: Links have been removed),

The revolutionary genetic technique better known for its potential to cure thousands of inherited diseases could also solve the challenge of Covid-19 diagnostic testing, scientists announced on Tuesday. A team headed by biologist Feng Zhang of the McGovern Institute at MIT and the Broad Institute has repurposed the genome-editing tool CRISPR into a test able to quickly detect as few as 100 coronavirus particles in a swab or saliva sample.

Crucially, the technique, dubbed a “one pot” protocol, works in a single test tube and does not require the many specialty chemicals, or reagents, whose shortage has hampered the rollout of widespread Covid-19 testing in the U.S. It takes about an hour to get results, requires minimal handling, and in preliminary studies has been highly accurate, Zhang told STAT. He and his colleagues, led by the McGovern’s Jonathan Gootenberg and Omar Abudayyeh, released the protocol on their STOPCovid.science website.

Because the test has not been approved by the Food and Drug Administration, it is only for research purposes for now. But minutes before speaking to STAT on Monday, Zhang and his colleagues were on a conference call with FDA officials about what they needed to do to receive an “emergency use authorization” that would allow clinical use of the test. The FDA has used EUAs to fast-track Covid-19 diagnostics as well as experimental therapies, including remdesivir, after less extensive testing than usually required.

For an EUA, the agency will require the scientists to validate the test, which they call STOPCovid, on dozens to hundreds of samples. Although “it is still early in the process,” Zhang said, he and his colleagues are confident enough in its accuracy that they are conferring with potential commercial partners who could turn the test into a cartridge-like device, similar to a pregnancy test, enabling Covid-19 testing at doctor offices and other point-of-care sites.

“It could potentially even be used at home or at workplaces,” Zhang said. “It’s inexpensive, does not require a lab, and can return results within an hour using a paper strip, not unlike a pregnancy test. This helps address the urgent need for widespread, accurate, inexpensive, and accessible Covid-19 testing.” Public health experts say the availability of such a test is one of the keys to safely reopening society, which will require widespread testing, and then tracing and possibly isolating the contacts of those who test positive.

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If you have time, do read Begley’s in full.