Use of such precision diagnostics offer ‘early detection, localization, and the opportunity to monitor response to therapy,’ say the MIT scientists
Oncologists and medical laboratory scientists know that most clinical laboratory tests currently used to diagnose cancer are either based on medical imaging technologies—such as CT scans and mammography—or on molecular diagnostics that detect cancer molecules in the body’s urine or blood.
Now, in a study being conducted at the Massachusetts Institute of Technology (MIT), researchers have developed diagnostic nanoparticles that can not only detect cancer cells in bodily fluids but also image the cancer’s location. This is the latest example of how scientists are combining technologies in new ways in their efforts to develop more sensitive diagnostic tests that clinical laboratories and other providers can use to detect cancer and other health conditions.
Precision diagnostics such as molecular, imaging, and analytics technologies are key tools in the pursuit of precision medicine.
“Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization, and the opportunity to monitor response to therapy,” the authors wrote, adding, “Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumor type.”
Development of Multimodal Diagnostics
The MIT scientists are developing a “multimodal” diagnostic that uses molecular screening combined with imaging techniques to locate where a cancer began in the body and any metastases that are present.
“In principle, this diagnostic could be used to detect cancer anywhere in the body, including tumors that have metastasized from their original locations,” an MIT new release noted.
“This is a really broad sensor intended to respond to both primary tumors and their metastases,” said biological engineer Sangeeta Bhatia, MD, PhD (above), in the news release. Bhatia is the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT and senior author of the study.
“It can trigger a urinary signal and also allow us to visualize where the tumors are,” she added. Bhatia previously worked on the development of cancer diagnostics that can produce synthetic biomarkers which are detectable in urine samples.
“The vision is that you could use this in a screening paradigm—alone or in conjunction with other tests—and we could collectively reach patients that do not have access to costly screening infrastructure today,” said Sangeeta Bhatia, MD, PhD (above), in the MIT news release. “Every year you could get a urine test as part of a general check-up. You would do an imaging study only if the urine test turns positive to then find out where the signal is coming from. We have a lot more work to do on the science to get there, but that’s where we would like to go in the long run.” (Photo copyright: NBC News.)
Precision Diagnostic Assists Assessment of Response to Cancer Therapy
For their research, the scientists added a radioactive tracer known as copper-64 to the nanoparticles. This enabled the particles to be used for positron emission tomography (PET) imaging. The particles were coated with a peptide that induced them to accumulate at tumor sites and insert themselves into cell membranes, producing a strong imaging signal for tumor detection.
The researchers tested their diagnostic nanoparticles in mouse models of metastatic colon cancer where tumor cells had traversed to the liver or the lungs. After treating the cancer cells with a chemotherapy regimen, the team successfully used both urine and imaging to determine how the tumors were responding to the treatment.
Bhatia is hopeful that this type of diagnostic could be utilized in assessing how patients are responding to treatment therapies and the monitoring of tumor recurrence or metastasis, especially for colon cancer.
What is unique about the approach used by Bhatia’s team is that one application of the copper-64 tracer can be used in vivo, in combination with imaging technology. The other application of the copper-64 tracer is in vitro in a urine specimen that can be tested by clinical laboratories.
“Those patients could be monitored with the urinary version of the test every six months, for instance. If the urine test is positive, they could follow up with a radioactive version of the same agent for an imaging study that could indicate where the disease had spread,” Bhatia said in the news release. “We also believe the regulatory path may be accelerated with both modes of testing leveraging a single formulation.”
The graphic above, taken from the MIT news release, shows how “multimodal nanosensors (1) are engineered to target and respond to hallmarks in the tumor microenvironment. The nanosensors provide both a noninvasive urinary monitoring tool (2) and an on-demand medical imaging agent (3) to localize tumor metastasis and assess response to therapy,” the news release states. (Photo and caption copyright: Massachusetts Institute of Technology.)
Precision Medicine Cancer Screening Using Nano Technologies
Bhatia hopes that the nanoparticle technology may be used as a screening tool in the future to detect any type of cancer.
Her previous research with nanoparticle technology determined that a simple urine test could diagnose bacterial pneumonia and indicate if antibiotics could successfully treat that illness, the news release noted.
Nanoparticle-based technology might be adapted in the future to be part of a screening assay that determines if cancer cells are present in a patient. In such a scenario, clinical laboratories would be performing tests on urine samples while imaging techniques are simultaneously being used to diagnose and monitor cancers.
Surgical pathologists may also want to monitor the progress of this research, as it has the potential to be an effective tool for monitoring cancer patients following surgery, chemotherapy, or radiation therapy.
AccuWeather interviewed experts, including pathologists who have analyzed the virus, who say SARS-CoV-2 is susceptible to heat, light, and humidity, while others study weather patterns for their predictions
AccuWeather, as it watched the outbreak of SARS-CoV-2, the novel coronavirus that causes COVID-19, wanted to know what effect that warmer spring temperatures might have on curbing the spread of the virus. There is a good reason to ask this question. As microbiologists, infectious disease doctors, and primary care physicians know, the typical start and end to every flu season is well-documented and closely watched.
As SARS-CoV-2 ravages countries around the world, clinical pathologists and microbiologists debate whether it will subside as temperatures rise in Spring and Summer. Recent analyses suggest it may indeed be a seasonal phenomenon. However, some infectious disease specialists have expressed skepticism.
CNN reported that Nicholls was part of a research team which reproduced the virus in January to study its behavior and evaluate diagnostic tests. Nicholls was also involved in an early effort to analyze the coronavirus associated with the 2003 SARS outbreak involving SARS-CoV, another coronavirus that originated in Asia.
“Sunlight will cut the virus’ ability to grow in half, so the half-life will be 2.5 minutes and in the dark it’s about 13 to 20,” Nicholls told AccuWeather. “Sunlight is really good at killing viruses.” And that, “In cold environments, there is longer virus survival than warm ones.” He added, “I think it will burn itself out in about six months.”
The graphic above, created by John Nicholls, MBBS Adel, FRCPA, FHKCPath, FHKAM (Pathology), Clinical Professor of Pathology at the University of Hong Kong, shows “the temperate zone where the major SARS-CoV-2 hotspots have appeared so far. The variation from year to year, in this case, is minimal; however, meteorologists would typically use the 30-year normal data for this type of analysis.” (Caption and graphic copyright: AccuWeather/John Nicholls.)
Can Weather Predict the Spread of COVID-19?
Other researchers have analyzed regional weather data to see if there’s a correlation with incidence of COVID-19. A team at the Massachusetts Institute of Technology (MIT) found that the number of cases has been relatively low in areas with warm, humid conditions and higher in more northerly regions. They published their findings in SSRN (formerly Social Science Research Network), an open-access journal and repository for early-stage research, titled “Will Coronavirus Pandemic Diminish by Summer?”
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The MIT researchers found that as of March 22, 90% of the
transmissions of SARS-CoV-2 occurred within a temperature range of three to 17
degrees Celsius (37.4 to 62.6 degrees Fahrenheit) and an absolute humidity
range of four to nine grams per cubic meter. Fewer than 6% of the transmissions
have been in warmer climates further south, they wrote.
“Based on the current data on the spread of [SARS-CoV-2], we
hypothesize that the lower number of cases in tropical countries might be due
to warm humid conditions, under which the spread of the virus might be slower
as has been observed for other viruses,” they wrote.
In the US, “the outbreak also shows a north-south divide,”
with higher incidence in northern states, they wrote. The outliers are Oregon,
with fewer than 200 cases, and Louisiana, where, as of March 22, approximately
1,000 had been reported.
There’s been a recent spike in reported cases from warmer
regions in Asia, South America, and Africa, but the MIT researchers attribute
this largely to increased testing.
Still, “there may be several caveats to our work,” they
wrote in their published study. For example, South Korea has been engaged in
widespread testing that includes asymptomatic individuals, whereas other
countries, including the US, have limited testing to a narrower range of
people, which could mean that more cases are going undetected. “Further, the
rate of outdoor transmission versus indoor and direct versus indirect
transmission are also not well understood and environmental related impacts are
mostly applicable to outdoor transmissions,” the MIT researchers wrote.
Even in warmer, more humid regions, they advocate “proper
quarantine measures” to limit the spread of the virus.
The New York Times (NYT) reported that other recent studies have shown a correlation between weather conditions and the incidence of COVID-19 outbreaks as well, though none of this research has been peer reviewed.
Why the Correlation? It’s Unclear, MIT Says
Though the MIT researchers found a strong relation between
the number of cases and weather conditions, “the underlying reasoning behind
this relationship is still not clear,” they wrote. “Similarly, we do not know
which environmental factor is more important. It could be that either
temperature or absolute humidity is more important, or both may be equally or
not important at all in the transmission of [SARS-CoV-2].”
Some experts have looked at older coronaviruses for clues. “The coronavirus is surrounded by a lipid layer, in other words, a layer of fat,” said molecular virologist Thomas Pietschmann, PhD, Director of the Department for Experimental Virology at the Helmholtz Center for Infection Research in Hanover, Germany, in a story from German news service Deutsche Welle. This makes it susceptible to temperature increases, he suggested.
However, Pietschmann cautioned that because it’s a new
virus, scientists cannot say if it will behave like older viruses. “Honestly
speaking, we do not know the virus yet,” he concluded.
Epidemiologist and virologist Joseph Fair, PhD, MPH (above), Special Advisor for Ebola, USAID, and Research Professor at Texas A&M University, said that sunlight might be a bigger factor than temperature or humidity. “It really doesn’t have anything to do with the warmth, but it has to do with the length of the day and the exposure to sunlight which inactivates the virus through UV light,” he told NBC News. “The science is still out,” he said. “We can assume this will follow typical other coronavirus cases,” but “everyone in the scientific and public health community expect it to be back in the fall and we expect to be in this for quite some time.” (Photo copyright: Texas A&M University.)
Marc Lipsitch, DPhil, Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health, is skeptical that warmer weather will put the brakes on COVID-19. “While we may expect modest declines in the contagiousness of SARS-CoV-2 in warmer, wetter weather, and perhaps with the closing of schools in temperate regions of the Northern Hemisphere, it is not reasonable to expect these declines alone to slow transmission enough to make a big dent,” he wrote in a commentary for the center.
How should pathologists and clinical laboratories in this country prepare for COVID-19? Lipsitch wrote that Influenza does tend to be seasonal, in part because cold, dry air is highly conducive to flu transmission. However, “for coronaviruses, the relevance of this factor is unknown.” And “new viruses have a temporary but important advantage—few or no individuals in the population are immune to them,” which means they are not as susceptible to the factors that constrain older viruses in warmer, more humid months.
So, we may not yet know enough to adequately prepare for
what’s coming. Nevertheless, monitoring the rapidly changing data on COVID-19
should be part of every lab’s daily agenda.
Genetic data captured by this new technology could lead to a new understanding of how different types of cells exchange information and would be a boon to anatomic pathology research worldwide
What if it were possible to map the interior of cells and view their genetic sequences using chemicals instead of light? Might that spark an entirely new way of studying human physiology? That’s what researchers at the Massachusetts Institute of Technology (MIT) believe. They have developed a new approach to visualizing cells and tissues that could enable the development of entirely new anatomic pathology tests that target a broad range of cancers and diseases.
Scientists at MIT’s Broad Institute and McGovern Institute for Brain Research developed this new technique, which they call DNA Microscopy. They published their findings in Cell, titled, “DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction.”
Joshua Weinstein, PhD, a postdoctoral associate at the Broad Institute and first author of the study, said in a news release that DNA microscopy “is an entirely new way of visualizing cells that captures both spatial and genetic information simultaneously from a single specimen. It will allow us to see how genetically unique cells—those comprising the immune system, cancer, or the gut for instance—interact with one another and give rise to complex multicellular life.”
The news release goes on to state that the new technology “shows
how biomolecules such as DNA and RNA are organized in cells and tissues,
revealing spatial and molecular information that is not easily accessible
through other microscopy methods. DNA microscopy also does not require
specialized equipment, enabling large numbers of samples to be processed
simultaneously.”
The images above, taken from the MIT study, compares optical imaging of a cell population (left) with an inferred visualization of the same cell population based on the information provided by DNA microscopy (right). Scale bar = 100 μm (100 micrometers). This technology has the potential to be useful for anatomic pathologists at some future date. (Photo and caption copyrights: Joshua Weinstein, PhD, et al/Cell.)
New Way to Visualize Cells
The MIT researchers saw an opportunity for DNA microscopy to
find genomic-level cell information. They claim that DNA microscopy images
cells from the inside and enables the capture of more data than with
traditional light microscopy. Their new technique is a chemical-encoded
approach to mapping cells that derives critical genetic insights from the
organization of the DNA and RNA in cells and tissue.
And that type of genetic information could lead to new precision medicine treatments for chronic disease. New Atlas notes that “ Speeding the development of immunotherapy treatments by identifying the immune cells best suited to target a particular cancer cell is but one of the many potential application for DNA microscopy.”
In their published study, the scientists note that “Despite enormous progress in molecular profiling of cellular constituents, spatially mapping [cells] remains a disjointed and specialized machinery-intensive process, relying on either light microscopy or direct physical registration. Here, we demonstrate DNA microscopy, a distinct imaging modality for scalable, optics-free mapping of relative biomolecule positions.”
How DNA Microscopy Works
The New York Times (NYT) notes that the advantage of DNA microscopy is “that it combines spatial details with scientists’ growing interest in—and ability to measure—precise genomic sequences, much as Google Street View integrates restaurant names and reviews into outlines of city blocks.”
And Singularity Hub notes that “ DNA microscopy, uses only a pipette and some liquid reagents. Rather than monitoring photons, here the team relies on ‘bar codes’ that chemically tag onto biomolecules. Like cell phone towers, the tags amplify, broadcasting their signals outward. An algorithm can then piece together the captured location data and transform those GPS-like digits into rainbow-colored photos. The results are absolutely breathtaking. Cells shine like stars in a nebula, each pseudo-colored according to their genomic profiles.”
“We’ve used DNA in a way that’s mathematically similar to photons in light microscopy,” Weinstein said in the Broad Institute news release. “This allows us to visualize biology as cells see it and not as the human eye does.”
In their study, researchers used DNA microscopy to tag RNA
molecules and map locations of individual human cancer cells. Their method is
“surprisingly simple” New Atlas reported. Here’s how it’s done,
according to the MIT news release:
Small synthetic DNA tags (dubbed “barcodes” by the MIT team) are added to biological samples;
The “tags” latch onto molecules of genetic material in the cells;
The tags are then replicated through a chemical reaction;
The tags combine and create more unique DNA labels;
The scientists use a DNA sequencer to decode and reconstruct the biomolecules;
A computer algorithm decodes the data and converts it to images displaying the biomolecules’ positions within the cells.
The visualization above was created from data gathered by DNA microscopy, which peers inside individual cells. It demonstrates how DNA microscopy enables scientists to identify different cells (colored dots) within a sample—with no prior knowledge of what the sample looks like. (Photo and caption copyright: Joshua Weinstein, PhD, et al./Cell.)
“The first time I saw a DNA microscopy image, it blew me away,” said Aviv Regev, PhD, a biologist at the Broad Institute, a Howard Hughes Medical Institute (HHMI) Investigator, and co-author of the MIT study, in an HHMI news release. “It’s an entirely new category of microscopy. It’s not just a technique; it’s a way of doing things that we haven’t ever considered doing before.”
Precision Medicine Potential
“Every cell has a unique make-up of DNA letters or genotype. By capturing information directly from the molecules being studied, DNA microscopy opens up a new way of connecting genotype to phenotype,” said Feng Zhang, PhD, MIT Neuroscience Professor,
Core Institute Member of the Broad Institute, and
Investigator at the McGovern Institute for Brain Research at MIT, in the HHMI
news release.
In other words, DNA microscopy could someday have applications in precision medicine. The MIT researchers, according to Stat, plan to expand the technology further to include immune cells that target cancer.
The Broad Institute has applied for a patent on DNA
microscopy. Clinical laboratory and anatomic pathology group leaders seeking
novel resources for diagnosis and treatment of cancer may want to follow the MIT
scientists’ progress.
“On-a-chip” devices continue to advance and medical laboratories will be natural repositories for patient data as the technology continues to improve
Dark Daily has predicted that the future of clinical laboratory testing will include highly complex multi-analyte test panels. The biomarkers, however, could number in the hundreds or thousands. So, it’s interesting to see new research by a Massachusetts Institute of Technology (MIT) team currently developing a multi-biomarker organ test device for clinical purposes.
Motivated by the costly failure of animal testing efforts to develop drug safety and efficacy in humans, the MIT research engineers created a microfluidic platform technology they dubbed “physiome-on-a-chip,” or more colloquially, “body-on-a-chip.” Their goal is to identify drug reaction in different cell groups within the body (in vivo).
They acknowledged contributions of in vitro microphysiological systems (MPSs), AKA “organ-on-a-chip” (OOC) systems. They note, however, in their paper published in Scientific Reports, that more complex systems that interconnect and receive data from multiple MPSs are needed due to increasing limitations arising from drugs’ “lack of efficacy” rather than toxicity.
“Here we describe the development and implementation of multi-MPS platforms, AKA physiome-on-a-chip, supporting four-way, seven-way, and 10-way MPS interactions for several weeks,” the MIT engineers wrote.
Though MIT’s new technology needs further research and development time, as well as clinical trials, this type of chip design and its ability to scale is a positive development and progress toward Dark Daily’s prediction. Once finalized, it could be adopted in medical laboratories for many types of diagnostic testing purposes.
Researchers Motivated to Improve Drug Efficacy
According to an MIT news release, “MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.”
The “body-on-a-chip” technology, MIT says, is aimed at determining how drugs may affect one organ while also having side effects on others.
“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic. With our chip, you can distribute a drug and then look for the effects on other tissues and measure the exposure and how it is metabolized,” said Linda Griffith, PhD, Professor of Teaching Innovation at MIT’s School of Engineering, and a senior author of the study, in the news release.
According to MIT, factors affecting the effectiveness of pharmaceuticals may include:
Genetics;
Environment;
Personal lifestyles; and,
Interactions with other drugs.
TechCrunch called the study “unprecedented,” pointing to the platform’s connection of so many tissues and the technology’s ability to keep them stable for weeks.
“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Linda Griffith, PhD, MIT Professor, MIT School of Engineering, told Science Daily. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.” (Photo copyright: MacArthur Foundation.)
How “Body-on-a-Chip” Works
“Body-on-a-chip” is about the size of a tablet computer and links 10 organ types, including: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle.
Using microfluidic platform technology, the researchers placed one- to two-million cells from human tissue samples into the device and then pushed fluid through the chip to resemble blood flow, the Daily Mail reported, adding that MIT’s MPS platform design features:
Compartments made from a plastic block;
Passages for fluid to move (as a circulatory system does) between the compartments;
A water reservoir to limit fluid evaporation; and,
Ability to monitor flow of molecular exchanges and drug distribution.
Essentially, using the MIT device, a drug can be introduced to one organ, processed normally, and then passed to other organs for processing and use in other ways, TechCrunch summarized.
The physiome-on-a-chip system (above schematic) comprises bioengineered devices that nurture many interconnected 3D MPSs representing specified functional behaviors of each organ of interest, designed to capture essential features of in vivo physiology based on quantitative systems models tailored for individual applications such as drug fate or disease modeling. This technology could eventually be utilized for clinical laboratory and anatomic pathology testing. (Image and caption copyright: Victor O. Leshyk/Scientific Reports.)
Drug Delivery, Effects on Multiple Tissues Noted in MIT Study
The MIT researcher engineers reported these findings and accomplishments:
Delivering a drug to the gastrointestinal tissue;
Replicating digesting a drug;
Observing as a drug was transported to other tissues and metabolized;
Measuring a drug’s path; and,
Noting effects of a drug on different tissues and how drugs break down.
“The huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitropharmacology. This study beautifully illustrates that multi-MPS ‘physiome-on-a-chip’ approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” said Kevin Healy, PhD, Professor of Bioengineering and Materials Science and Engineering, at University of California Berkeley in the MIT news release. Healy was not involved in the research.
Unique Device Design
In addition to making it possible to study so many different tissue types, the device design, according to MIT, is unique for these reasons:
Its open microfluidic system, rather than a closed system, means the lid can be removed to manipulate tissue samples;
Instead of external pumps common in closed systems, the MIT team used “on-board pumps” to control flow of liquid between the organs; and,
The pumps used enabled larger engineered tissues, such as those from tumors in an organ, to be assessed.
The MIT engineers next plan to focus on specific organs—including the brain, liver, and gastrointestinal tissue—to model Parkinson’s disease, Digital Trends reported.
As healthcare providers and medical laboratories adopt precision medicine, MIT’s contributions are both timely and important. The ability to accommodate many different configurations in one platform is impressive, and something Dark Daily has been anticipating.
Three innovative technologies utilizing CRISPR-Cas13, Cas12a, and Cas9 demonstrate how CRISPR might be used for more than gene editing, while highlighting potential to develop new diagnostics for both the medical laboratory and point-of-care (POC) testing markets
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is in the news again! The remarkable genetic-editing technology is at the core of several important developments in clinical laboratory and anatomic pathology diagnostics, which Dark Daily has covered in detail for years.
Now, scientists at three universities are investigating ways to expand CRISPR’s use. They are using CRISPR to develop new diagnostic tests, or to enhance the sensitivity of existing DNA tests.
One such advancement improves the sensitivity of SHERLOCK (Specific High Sensitivity Reporter unLOCKing), a CRISPR-based diagnostic tool developed by a team at MIT. The new development harnesses the DNA slicing traits of CRISPR to adapt it as a multifunctional tool capable of acting as a biosensor. This has resulted in a paper-strip test, much like a pregnancy test, that can that can “display test results for a single genetic signature,” according to MIT News.
Such a medical laboratory test would be highly useful during pandemics and in rural environments that lack critical resources, such as electricity and clean water.
One Hundred Times More Sensitive Medical Laboratory Tests!
MIT News highlighted the high specificity and ease-of-use of their system in detecting Zika and Dengue viruses simultaneously. However, researchers stated that the system can target any genetic sequence. “With the original SHERLOCK, we were detecting a single molecule in a microliter, but now we can achieve 100-fold greater sensitivity … That’s especially important for applications like detecting cell-free tumor DNA in blood samples, where the concentration of your target might be extremely low,” noted Abudayyeh.
“The [CRISPR] technology demonstrates potential for many healthcare applications, including diagnosing infections in patients and detecting mutations that confer drug resistance or cause cancer,” stated senior authorFeng Zhang, PhD. Zhang, shown above in the MIT lab named after him, is a Core Institute Member of the Broad Institute, Associate Professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT, and a pioneer in the development of CRISPR gene-editing tools. (Photo copyright: MIT.)
Creating a Cellular “Black Box” using CRISPR
Another unique use of CRISPR technology involved researchers David Liu, PhD, and Weixin Tang, PhD, of Harvard University and Howard Hughes Medical Institute (HHMI). Working in the Feng Zhang laboratory at the Broad Institute, they developed a sort of “data recorder” that records events as CRISPR-Cas9 is used to remove portions of a cell’s DNA.
They published the results of their development of CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems, in Science. The story was also covered by STAT.
“The order of stimuli can be recorded through an overlapping guide RNA design and memories can be erased and re-recorded over multiple cycles,” the researchers noted. “CAMERA systems serve as ‘cell data recorders’ that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.”
This creates a system much like the “black box” recorders in aircraft. However, using Cas9, data is recorded at the cellular level. “There are a lot of questions in cell biology where you’d like to know a cell’s history,” Liu told STAT.
While researchers acknowledge that any medical applications are in the far future, the technology holds the potential to capture and replay activity on the cellular level—a potentially powerful tool for oncologists, pathologists, and other medical specialists.
Using CRISPR to Detect Viruses and Infectious Diseases
Another recently developed technology—DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR)—shows even greater promise for utility to anatomic pathology groups and clinical laboratories.
Also recently debuted in Science, the DETECTR system is a product of Jennifer Doudna, PhD, and a team of researchers at the University of California Berkeley and HHMI. It uses CRISPR-Cas12a’s indiscriminate single-stranded DNA cleaving as a biosensor to detect different human papillomaviruses (HPVs). Once detected, it signals to indicate the presence of HPV in human cells.
Despite the current focus on HPVs, the researchers told Gizmodo they believe the same methods could identify other viral or bacterial infections, detect cancer biomarkers, and uncover chromosomal abnormalities.
Future Impact on Clinical Laboratories of CRISPR-based Diagnostics
Each of these new methods highlights the abilities of CRISPR both as a data generation tool and a biosensor. While still in the research phases, they offer yet another possibility of improving efficiency, targeting specific diseases and pathogens, and creating new assays and diagnostics to expand medical laboratory testing menus and power the precision medicine treatments of the future.
As CRISPR-based diagnostics mature, medical laboratory directors might find that new capabilities and assays featuring these technologies offer new avenues for remaining competitive and maintaining margins.
However, as SHERLOCK demonstrates, it also highlights the push for tests that produce results with high-specificity, but which do not require specialized medical laboratory training and expensive hardware to read. Similar approaches could power the next generation of POC tests, which certainly would affect the volume, and therefore the revenue, of independent clinical laboratories and hospital/health system core laboratories.
