Tag Archives: Alisha Goodbla

The Broad Institute gives us another reason to love CRISPR

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.

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.