Beyond Scissors: CRISPR as a Diagnostic Tool
When most people hear "CRISPR," they picture molecular scissors snipping DNA to cure genetic diseases. That image is accurate but incomplete. Some of the most impactful applications of CRISPR technology have nothing to do with editing genes at all. Instead, they harness the same molecular machinery to detect specific genetic sequences -- and in doing so, they are building a new generation of diagnostic tools that could be faster, cheaper, and more portable than anything that currently exists.
The idea is elegantly simple. CRISPR systems evolved in bacteria as an immune defense: when a virus infects a bacterial cell, the CRISPR system recognizes the viral DNA and destroys it. Researchers realized that this recognition ability -- the capacity to find one specific genetic sequence in a complex biological sample -- is exactly what diagnostics require. If you can program CRISPR to search for a snippet of SARS-CoV-2 RNA, or a cancer-associated mutation, or the genome of a sexually transmitted pathogen, you have the foundation for a powerful detection platform.
Two competing platforms emerged from this insight, developed independently by two of the most prominent laboratories in gene editing. SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) came from Feng Zhang's lab at the Broad Institute. DETECTR (DNA Endonuclease-Targeted CRISPR Trans Reporter) was developed by Jennifer Doudna's group at UC Berkeley. Both exploit a peculiar enzymatic behavior called collateral cleavage -- and both have the potential to transform how the world diagnoses disease.
"We realized that the same molecular tools we were using to edit genomes could be repurposed to detect virtually any nucleic acid sequence with extraordinary sensitivity," said Feng Zhang, a core member of the Broad Institute and co-founder of Sherlock Biosciences, in a 2020 interview with Nature Biotechnology. "The diagnostic application may ultimately reach more people than gene editing itself."
Lateral flow strips -- the same format used in home pregnancy tests and COVID rapid tests -- are now being adapted for CRISPR-based diagnostics, offering molecular-level sensitivity in a paper strip format. Image: Wikimedia Commons, CC BY-SA 4.0.
The Science: How CRISPR Finds Disease
To understand CRISPR diagnostics, you need to understand one key concept that separates detection from editing: collateral cleavage.
Collateral Cleavage: The Secret Weapon
In CRISPR gene editing, the Cas9 enzyme is guided to a specific DNA sequence by a guide RNA. Once it finds its target, Cas9 cuts the double-stranded DNA at that precise location and then stops. It is a single, targeted cut -- clean and contained.
But not all Cas enzymes behave so neatly. Cas12a and Cas13 -- members of the broader CRISPR-associated protein family -- have a different property. When these enzymes find and bind their programmed target, they become activated. And once activated, they do not just cut the target. They begin indiscriminately slicing any nearby single-stranded nucleic acids. Cas12a chews through single-stranded DNA. Cas13 shreds single-stranded RNA. This uncontrolled degradation of bystander molecules is called collateral cleavage, and in the context of gene editing, it would be a liability -- a reckless enzyme that destroys nearby genetic material is not what you want when precision is the goal.
But for diagnostics, collateral cleavage is a gift. Here is why.
Turning Molecular Chaos Into a Signal
Researchers exploit collateral cleavage by adding reporter molecules to the reaction mix. These are short, synthetic nucleic acid sequences attached to a fluorescent tag on one end and a quencher molecule on the other. When the reporter is intact, the quencher absorbs the fluorescent signal -- no glow, no signal. But when a collaterally activated Cas12a or Cas13 enzyme chops the reporter molecule in half, the fluorescent tag is freed from the quencher, and the sample lights up.
The logic chain is straightforward:
- Target present -- Guide RNA finds the pathogen's genetic material and activates the Cas enzyme.
- Collateral cleavage begins -- The activated enzyme starts cutting all nearby single-stranded nucleic acids, including the reporter molecules.
- Signal generated -- Cleaved reporters release their fluorescent tags, producing a measurable glow.
- Target absent -- No activation, no collateral cleavage, no signal.
Because a single activated Cas enzyme can cleave thousands of reporter molecules, the signal is amplified enormously without needing complex equipment. This built-in amplification is what gives CRISPR diagnostics their remarkable sensitivity.
SHERLOCK: Cas13 and RNA Detection
SHERLOCK was first described in a 2017 paper published in Science by Feng Zhang, Omar Abudayyeh, Jonathan Gootenberg, and colleagues at the Broad Institute. The platform uses Cas13a, a CRISPR enzyme that targets single-stranded RNA.
The SHERLOCK workflow begins with a sample -- a nasal swab, a blood draw, a urine sample. The nucleic acids in the sample are first amplified using Recombinase Polymerase Amplification (RPA), an isothermal amplification method that works at body temperature and does not require a thermal cycler. The amplified DNA is then converted to RNA using a T7 transcription step, and the resulting RNA is exposed to Cas13a programmed with a guide RNA matching the target sequence.
If the target RNA is present, Cas13a activates and begins its collateral cleavage rampage, cutting reporter molecules and generating a fluorescent signal. The entire process, from sample to result, takes approximately one hour and can achieve sensitivity in the attomolar range -- detecting as few as a single molecule of target RNA in a microliter of sample.
A refined version, SHERLOCKv2, published in 2018, added multiplexing capability. By using multiple Cas13 orthologs from different bacterial species -- each with a preference for different reporter sequences tagged with different-colored fluorescent labels -- SHERLOCKv2 can detect up to four different targets simultaneously in a single reaction. This is particularly useful for distinguishing between closely related pathogens, such as different strains of influenza or different species of Zika and Dengue viruses.
DETECTR: Cas12a and DNA Detection
DETECTR was published in Science in 2018 by Jennifer Doudna, Janice Chen, and Lucas Harrington at UC Berkeley. While SHERLOCK uses Cas13a to detect RNA, DETECTR uses Cas12a (also known as Cpf1) to detect double-stranded DNA.
The workflow is similar: nucleic acids are amplified from the clinical sample using isothermal amplification, then exposed to Cas12a programmed with a target-specific guide RNA. If the target DNA is present, Cas12a binds it, activates, and begins collaterally cleaving single-stranded DNA reporter molecules.
DETECTR was initially demonstrated by detecting human papillomavirus (HPV) types 16 and 18 -- the high-risk strains responsible for cervical cancer. The assay distinguished between the two HPV types with perfect accuracy in clinical samples, completing the analysis in under an hour.
"What excited us was not just the sensitivity, but the specificity," said Jennifer Doudna, Nobel Laureate and co-founder of Mammoth Biosciences, in a 2018 press briefing. "CRISPR can distinguish between sequences that differ by a single nucleotide. That level of discrimination is difficult to achieve with other rapid diagnostic approaches."
COVID-19: CRISPR Diagnostics Meet a Pandemic
The COVID-19 pandemic became the first real-world stress test for CRISPR diagnostics. When SARS-CoV-2 emerged in late 2019, the standard diagnostic was RT-qPCR -- a laboratory-based molecular test that amplifies viral RNA using a thermal cycler. RT-qPCR is highly accurate, but it requires expensive equipment, trained technicians, and centralized lab infrastructure. In the early months of the pandemic, testing bottlenecks became a global crisis. Labs were overwhelmed, turnaround times stretched to a week or more, and millions of people could not access testing at all.
Both SHERLOCK and DETECTR teams pivoted immediately to SARS-CoV-2 detection.
Sherlock Biosciences and the SHERLOCK Protocol
Zhang's team published a SHERLOCK-based SARS-CoV-2 detection protocol in February 2020 -- remarkably early in the pandemic timeline. The protocol targeted two genes in the SARS-CoV-2 genome (the S gene and the Orf1ab gene) and could deliver results in under an hour using only a simple heat block and lateral flow paper strips.
In May 2020, Sherlock Biosciences received the first-ever FDA Emergency Use Authorization (EUA) for a CRISPR-based diagnostic test. The authorized test, called Sherlock CRISPR SARS-CoV-2, could detect the virus with sensitivity comparable to RT-qPCR but without the need for a thermal cycler or sophisticated laboratory equipment. This was a watershed moment for the field -- the first regulatory validation that CRISPR diagnostics could meet clinical-grade standards.
Mammoth Biosciences and DETECTR
Mammoth Biosciences, the company Doudna co-founded to commercialize DETECTR, also developed a SARS-CoV-2 test. Their DETECTR-based assay targeted the N gene and E gene of the virus, using isothermal amplification followed by Cas12a-mediated detection. The test delivered results in approximately 30-40 minutes with sensitivity comparable to RT-qPCR.
Mammoth received its own FDA EUA for a high-throughput CRISPR-based SARS-CoV-2 test designed for clinical laboratories, further validating the platform's reliability.
STOPCovid: The Paper Strip Vision
Perhaps the most ambitious COVID-era development was STOPCovid (SHERLOCK Testing in One Pot), developed by Zhang's group and published in the New England Journal of Medicine in 2020. STOPCovid simplified the multi-step SHERLOCK protocol into a single reaction tube that could be read with a lateral flow paper strip -- the same format used in home pregnancy tests. The entire process required only a single temperature incubation step (around 60 degrees Celsius, achievable with a simple water bath or even a hand warmer) and delivered results visible to the naked eye within 70 minutes.
The estimated cost per test: under $1 for materials.
While STOPCovid did not reach mass commercial deployment during the pandemic -- rapid antigen tests from established diagnostics companies filled the immediate need -- it demonstrated a proof of concept that has enormous implications for future outbreaks: a molecular-precision diagnostic test that costs a dollar, requires no electricity beyond a heat source, and can be manufactured on paper strips at massive scale.
A PCR thermal cycler -- the gold standard for molecular diagnostics -- costs $15,000-$90,000 and requires trained operators. CRISPR diagnostics aim to deliver comparable accuracy without any of this infrastructure. Image: Wikimedia Commons, CC BY-SA 4.0.
CRISPR vs. PCR: Why It Matters
To appreciate why CRISPR diagnostics are significant, it helps to understand the limitations of the technology they aim to supplement -- and eventually, in some applications, replace.
RT-qPCR (reverse transcription quantitative polymerase chain reaction) has been the gold standard for molecular diagnostics since the 1990s. It detects pathogens by amplifying their genetic material through repeated cycles of heating and cooling -- typically 30-40 cycles, each requiring precise temperature changes. The technology is extraordinarily sensitive and well-validated.
But PCR has structural limitations that constrain where and how it can be used:
| Feature | RT-qPCR | CRISPR Diagnostics (SHERLOCK/DETECTR) |
|---|---|---|
| Equipment cost | $15,000-$90,000 (thermal cycler) | $0-$100 (heat block or water bath) |
| Time to result | 1-4 hours (plus transport time) | 30-60 minutes |
| Lab infrastructure | Required (BSL-2, trained staff) | Minimal to none |
| Cost per test | $50-$150 | $1-$10 (target) |
| Temperature control | Precise cycling (55-95C) | Single temperature (isothermal) |
| Sensitivity | Attomolar (gold standard) | Attomolar (comparable with amplification) |
| Readout | Fluorescence (requires reader) | Lateral flow strip (naked eye) |
| Multiplexing | Limited per reaction | Up to 4 targets (SHERLOCKv2) |
| Point-of-care use | Not practical | Designed for it |
The key advantages of CRISPR diagnostics are not about replacing PCR in well-equipped hospitals and research labs. PCR will remain the workhorse in those settings. The advantage is about reaching the places PCR cannot go: rural clinics in sub-Saharan Africa, forward-deployed military units, agricultural fields, veterinary offices, and eventually, the home medicine cabinet.
"Diagnostics only matter if they reach the people who need them," said James Collins, a bioengineer at MIT who collaborated with Zhang on freeze-dried CRISPR diagnostic platforms. "A test that sits in a central lab is useless for a farmer in sub-Saharan Africa who needs to know if their crops have a viral infection, or a community health worker screening for TB in a remote village."
Cancer Detection: Liquid Biopsies and CRISPR
While infectious disease was the first proving ground, CRISPR diagnostics are now pushing into a far larger clinical opportunity: cancer detection.
The Liquid Biopsy Revolution
Tumors shed fragments of their DNA into the bloodstream. These fragments, called circulating tumor DNA (ctDNA), carry the same mutations present in the tumor itself. A simple blood draw -- a "liquid biopsy" -- can capture these fragments, and if you have a diagnostic sensitive enough to detect them among the vast background of normal cell-free DNA, you can identify cancers without invasive tissue biopsies, track treatment response, and detect recurrence earlier than imaging.
The problem is sensitivity. ctDNA is vanishingly rare in early-stage cancers -- sometimes constituting less than 0.01% of total cell-free DNA in the blood. Current liquid biopsy technologies based on next-generation sequencing (NGS) are effective but expensive ($1,000-$5,000 per test) and slow (days to weeks for results).
CRISPR diagnostics offer a potential shortcut. Because the collateral cleavage mechanism amplifies signal from even a tiny amount of target DNA, CRISPR-based assays can theoretically detect cancer-associated mutations at very low concentrations with faster turnaround and lower cost than NGS.
CRISPR-Based Cancer Detection in Research
Several research groups have demonstrated CRISPR-based detection of cancer biomarkers:
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KRAS mutations: Researchers at the University of California published a CRISPR-Cas12a assay in 2019 that detected KRAS G12D mutations -- one of the most common oncogenic mutations, found in pancreatic, colorectal, and lung cancers -- directly from plasma samples. The assay distinguished mutant from wild-type sequences with single-nucleotide specificity, a level of discrimination that is critical for detecting low-frequency cancer mutations against a background of normal DNA.
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EGFR mutations: A Cas13-based platform demonstrated detection of EGFR T790M mutations in non-small cell lung cancer patients, identifying the resistance mutation that determines whether a patient should switch from first-generation to third-generation tyrosine kinase inhibitors. The assay achieved results in under two hours from a blood sample.
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HPV-associated cancers: DETECTR's original demonstration -- distinguishing HPV16 from HPV18 -- has direct relevance to cervical cancer screening. In resource-limited settings where Pap smears and colposcopy are not readily available, a CRISPR-based HPV test that works on a paper strip could be transformative.
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Methylation detection: In 2021, researchers demonstrated a CRISPR-based system called DISQVER that could detect cancer-associated DNA methylation patterns in liquid biopsy samples. Aberrant methylation is an early hallmark of many cancers and is more abundant in the blood than point mutations, making it an attractive target for early detection.
Mammoth Biosciences has publicly stated that oncology diagnostics are a core part of its long-term platform strategy, though the company's initial commercial focus has been on infectious disease testing where the regulatory pathway is more straightforward.
Beyond Human Health: Agricultural and Environmental Applications
The diagnostic potential of CRISPR extends well beyond human medicine. In agriculture, rapid pathogen detection can mean the difference between saving a crop and losing an entire harvest.
Crop Disease Detection
Plant pathogens -- viruses, bacteria, and fungi -- cause an estimated $220 billion in crop losses globally each year, according to the FAO. Current diagnostic methods for plant diseases often require sending samples to specialized agricultural laboratories and waiting days for PCR results. By the time results arrive, the disease may have already spread to neighboring fields.
CRISPR-based diagnostics could enable in-field testing by agricultural workers. Several proof-of-concept studies have demonstrated CRISPR detection of:
- Citrus greening disease (Huanglongbing), caused by the bacterium Candidatus Liberibacter, which has devastated citrus orchards in Florida, Brazil, and China
- Cassava mosaic virus, a major threat to food security in sub-Saharan Africa
- Wheat blast fungus (Magnaporthe oryzae pathotype Triticum), an emerging threat to global wheat production
A field worker could, in principle, crush a leaf sample, add it to a CRISPR diagnostic cartridge, and read the result on a paper strip within an hour -- no lab, no training beyond basic instruction.
STI Testing and Public Health
Sexually transmitted infections represent another area where the speed, cost, and privacy advantages of CRISPR diagnostics could have outsized impact. Current testing for chlamydia, gonorrhea, and HPV typically requires a clinic visit and a centralized lab. SHERLOCK-based assays have been demonstrated for multiple STI pathogens, and the prospect of accurate, confidential, at-home STI testing with CRISPR-based paper strip tests is under active exploration.
The public health implications are significant. The WHO estimates that more than one million STIs are acquired daily worldwide, and a substantial fraction go undiagnosed due to stigma, cost, or access barriers. A $1-$5 CRISPR test that can be used at home and read without equipment could fundamentally alter STI surveillance and treatment.
The Commercial Landscape
Mammoth Biosciences
Founded in 2017 by Jennifer Doudna, Janice Chen, Lucas Harrington, and Trevor Martin, Mammoth Biosciences is the commercial vehicle for DETECTR technology. The company has raised over $400 million in venture funding and has positioned itself as a broad CRISPR platform company spanning both diagnostics and therapeutics.
On the diagnostics side, Mammoth's strategy centers on what it calls "programmable biology" -- the idea that a single CRISPR-based platform can be rapidly reprogrammed to detect any genetic target simply by swapping out the guide RNA. This modularity is a key advantage over traditional diagnostic development, where each new test often requires months or years of bespoke assay development.
Mammoth has partnerships with major diagnostics companies, including a collaboration with GlaxoSmithKline (GSK) for clinical applications and agreements with contract diagnostic manufacturers for commercial test production. The company has also built a proprietary library of novel Cas enzymes discovered through metagenomic mining of environmental samples -- identifying CRISPR proteins from bacteria that have never been cultured in a laboratory, some of which have properties (smaller size, different temperature optima, alternative PAM requirements) that could expand the diagnostic toolkit.
Sherlock Biosciences
Founded in 2019 by Feng Zhang, Omar Abudayyeh, Jonathan Gootenberg, Jim Collins, Rahul Dhanda, and others, Sherlock Biosciences holds the commercial license for SHERLOCK technology. The company has pursued a dual-technology strategy, combining CRISPR-based detection with a complementary synthetic biology platform called INSPECTR (Internal Splint-Pairing Enabled CRISPR Triggered Reaction), which uses engineered genetic circuits to detect target molecules.
Sherlock Biosciences' most notable achievement remains the first FDA EUA for a CRISPR diagnostic, granted for its SARS-CoV-2 test in May 2020. The company has since expanded its pipeline to include tests for respiratory pathogens, drug-resistant tuberculosis, and other infectious diseases.
Other Players
The CRISPR diagnostics field has attracted additional entrants:
- Caspr Biotech (Argentina/USA) developed a CRISPR-Cas12a platform for pathogen detection and received investment from Y Combinator.
- Tolo Biotech (China) has commercialized CRISPR-based diagnostics for veterinary and agricultural applications in the Chinese market.
- Cardea Bio (formerly Nanosens) developed a CRISPR-Chip that combines CRISPR with graphene-based transistors to detect DNA mutations without amplification -- a potential breakthrough for true point-of-care use if the approach can be scaled.
Challenges and Limitations
Despite the promise, CRISPR diagnostics face real hurdles on the path to widespread clinical adoption.
Sensitivity Without Amplification
The core CRISPR detection step -- Cas enzyme activation and collateral cleavage -- is highly specific but not inherently sensitive enough to detect the extremely low concentrations of pathogen nucleic acids present in many clinical samples. This is why both SHERLOCK and DETECTR rely on a pre-amplification step (RPA, LAMP, or other isothermal methods) before the CRISPR detection step.
This amplification step adds complexity, introduces potential for contamination, and requires additional reagents. A true "amplification-free" CRISPR diagnostic would be simpler and faster, but achieving clinical-grade sensitivity without amplification remains an active research challenge. Some progress has been made -- the Cardea Bio CRISPR-Chip and electrochemical CRISPR sensors have demonstrated amplification-free detection of moderate-concentration targets -- but none have yet matched the sensitivity of amplification-assisted protocols.
Regulatory Pathways
The FDA EUA pathway used during the COVID pandemic was an accelerated route. For routine clinical diagnostics outside a public health emergency, CRISPR-based tests will need to navigate the standard 510(k) or de novo classification pathways, which require extensive analytical and clinical validation. This is a multi-year, multi-million-dollar process for each individual test, and it represents a significant barrier for a technology whose key advantage is supposed to be rapid reprogrammability.
Regulatory frameworks in the EU (CE-IVDR), China (NMPA), and other jurisdictions present additional complexity. The lack of a clear regulatory category for "programmable molecular diagnostics" -- a platform that can be rapidly adapted to new targets -- is a structural challenge that industry and regulators are still working to resolve.
Manufacturing and Distribution
Paper-strip lateral flow tests sound simple, but manufacturing them at scale with consistent quality requires significant investment in production infrastructure. The freeze-dried reagent formats that make CRISPR tests shelf-stable and room-temperature-compatible are still being optimized for mass production. Supply chain challenges -- particularly for specialized enzymes and synthetic nucleic acids -- could constrain rapid scale-up during a future pandemic.
Competition from Established Technologies
CRISPR diagnostics are entering a market with deeply entrenched incumbents. Companies like Roche, Abbott, Hologic, and Cepheid have spent decades building installed bases of PCR instruments, reagent supply chains, and clinical validation data. Hospital lab directors are understandably cautious about adopting new platforms when their existing workflows meet clinical needs. CRISPR's advantages are most compelling in decentralized, point-of-care, and resource-limited settings -- markets that the large diagnostic companies have historically underserved.
The Future: Smartphone Diagnostics and Multiplexed Panels
The trajectory of CRISPR diagnostics points toward increasingly integrated, connected, and multiplexed systems.
Smartphone-Connected Testing
Several research groups have demonstrated CRISPR diagnostic readouts using smartphone cameras. The fluorescent or colorimetric signals generated by collateral cleavage can be imaged by a phone camera and analyzed by an app, enabling quantitative results, automatic data logging, geo-tagged epidemiological surveillance, and telemedicine integration. A 2021 paper in Nature Biomedical Engineering described a smartphone-based CRISPR diagnostic that detected SARS-CoV-2 from nasal swabs with results sent directly to a cloud-based public health dashboard.
This vision -- a molecular-precision diagnostic that fits in a pocket, connects to a phone, and feeds data to public health authorities in real time -- represents a fundamental departure from the centralized laboratory model that has dominated diagnostics for a century.
Multiplexed Panels
The ability to detect multiple targets simultaneously is critical for clinical utility. Many infectious syndromes -- respiratory illness, febrile illness, gastroenteritis -- can be caused by dozens of different pathogens, and determining the correct cause requires a panel test rather than a single-target assay.
SHERLOCKv2 demonstrated four-target multiplexing in 2018. More recent work has pushed this further. A platform called CARMEN (Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids), published in Nature in 2020 by the Zhang lab, combined SHERLOCK with microfluidic droplet technology to test a single sample against more than 4,500 guide RNA-target combinations simultaneously. CARMEN was used to detect 169 human-associated viruses from a single sample -- a capability that could revolutionize pandemic surveillance and syndromic testing.
Wearable and Continuous Monitoring
Looking further ahead, researchers are exploring CRISPR-based biosensors that could be integrated into wearable devices for continuous health monitoring. A freeze-dried CRISPR reaction embedded in a wearable patch that samples interstitial fluid could, in theory, provide continuous surveillance for pathogen exposure, cancer biomarker levels, or metabolic markers. This remains speculative and faces formidable engineering challenges, but it illustrates the breadth of the platform's potential.
What This Means for Global Health
The ultimate promise of CRISPR diagnostics is not about replacing PCR in wealthy countries with well-funded hospital systems. It is about democratizing access to molecular diagnostics globally.
The WHO estimates that nearly half the world's population lacks access to essential diagnostic services. In many low- and middle-income countries, the nearest PCR-capable laboratory may be hundreds of kilometers away. Diseases that are easily treatable when caught early -- tuberculosis, malaria, HIV, HPV-driven cervical cancer -- kill millions of people each year in part because they are diagnosed too late or not at all.
A diagnostic platform that works on a paper strip, costs a dollar, needs no electricity, and can be deployed by a community health worker with minimal training has the potential to fundamentally alter this equation. CRISPR diagnostics are not there yet. The technology works in the laboratory; the challenge is engineering, manufacturing, regulatory approval, and distribution at the scale required to make a difference.
But the trajectory is clear. The same molecular system that bacteria evolved billions of years ago to detect viral invaders is being repurposed to detect the full spectrum of human, animal, and plant pathogens. CRISPR's diagnostic future may ultimately prove as transformative as its therapeutic one -- and it may reach far more people.
As Trevor Martin, co-founder and CEO of Mammoth Biosciences, told STAT News in 2023: "We think of CRISPR as a search engine for biology. You give it a query -- any genetic sequence you want to find -- and it returns a yes or no answer. That fundamental capability applies to any disease, any pathogen, any mutation. The question is no longer whether CRISPR diagnostics work. It's how fast we can get them to the people who need them."
Sources & Further Reading
- Gootenberg, J.S. et al. "Nucleic acid detection with CRISPR-Cas13a/C2c2." Science 356, 438-442 (2017) — The original SHERLOCK paper describing Cas13-based diagnostics.
- Chen, J.S. et al. "CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity." Science 360, 436-439 (2018) — The DETECTR paper from Doudna's group at UC Berkeley.
- Joung, J. et al. "Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing." New England Journal of Medicine 383, 1492-1494 (2020) — STOPCovid protocol for simplified COVID detection.
- Ackerman, C.M. et al. "Massively multiplexed nucleic acid detection with Cas13." Nature 582, 277-282 (2020) — The CARMEN platform for detecting 169 viruses simultaneously.
- Broughton, J.P. et al. "CRISPR-Cas12-based detection of SARS-CoV-2." Nature Biotechnology 38, 870-874 (2020) — Mammoth/UC Berkeley DETECTR protocol for COVID-19.
- Fozouni, P. et al. "Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy." Cell 184, 323-333 (2021) — Smartphone-connected CRISPR diagnostics from Doudna's group.
- FDA Emergency Use Authorizations for CRISPR-based diagnostics (FDA.gov) — Regulatory record of SHERLOCK SARS-CoV-2 EUA.
- Kellner, M.J. et al. "SHERLOCK: nucleic acid detection with CRISPR nucleases." Nature Protocols 14, 2986-3012 (2019) — Detailed laboratory protocol for SHERLOCK implementation.
- Mammoth Biosciences — CRISPR Diagnostics Platform Overview — Company pipeline and diagnostic technology description.
- Sherlock Biosciences — CRISPR-Powered Diagnostics — Company information and SHERLOCK technology background.
- Li, S.Y. et al. "CRISPR-Cas12a-assisted nucleic acid detection." Cell Discovery 4, 20 (2018) — Early demonstration of Cas12a diagnostic applications.
- World Health Organization. "Access to diagnostics: a critical component of universal health coverage." — WHO data on global diagnostic access gaps.
Last updated: December 2025.
