Apr 18, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
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!
Co-lead authors Jonathan Gootenberg, PhD Candidate, Harvard University and Broad Institute; and Omar Abudayyeh, PhD and MD student, MIT, published their findings in Science. They used CRISPR Cas13 and Cas12a to chop up RNA in a sample and RNA-guided DNA binding to target genetic sequences. Presence of targeted sequences is then indicated using a paper-based testing strip like those used in consumer pregnancy 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 author Feng 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.)
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.
—Jon Stone
Related Information:
Multiplexed and Portable Nucleic Acid Detection Platform with Cas13, Cas12a, and Csm6
Rewritable Multi-Event Analog Recording in Bacterial and Mammalian Cells
CRISPR-Cas12a Target Binding Unleashes Indiscriminate Single-Stranded DNase Activity
Researchers Advance CRISPR-Based Tool for Diagnosing Disease
CRISPR Isn’t Just for Gene Editing Anymore
CRISPR’s Pioneers Find a Way to Use It as a Glowing Virus Detector
With New CRISPR Inventions, Its Pioneers Say, You Ain’t Seen Nothin’ Yet
New CRISPR Tools Can Detect Infections Like HPV, Dengue, and Zika
Breakthrough DNA Editing Tool May Help Pathologists Develop New Diagnostic Approaches to Identify and Treat the Underlying Causes of Diseases at the Genetic Level
CRISPR-Related Tool Set to Fundamentally Change Clinical Laboratory Diagnostics, Especially in Rural and Remote Locations
Harvard Researchers Demonstrate a New Method to Deliver Gene-editing Proteins into Cells: Possibly Creating a New Diagnostic Opportunity for Pathologists
Feb 21, 2018 | Instruments & Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
It has been regularly demonstrated in recent decades that human breath contains elements that could be incorporated into clinical laboratory tests, so the decision to use this “breath biopsy” test in a therapeutic drug trial will be closely watched
When a major pharma company pays attention to a breath test, implications for clinical laboratories are often forthcoming. Such may be the case with GlaxoSmithKline (GSK). The global healthcare company has selected Owlstone Medical’s Breath Biopsy technology for use in its Phase II clinical trial of danirixin (DNX), a respiratory drug under development by GSK for treatment of chronic obstructive pulmonary disease (COPD), an Owlstone Medical news release announced.
Anatomic pathologists and medical laboratory leaders will be intrigued by GSK’s integration of breath-based specimens in a clinical trial of a respiratory drug. The partners in the trial aim to analyze breath samples to better understand the drug’s treatment effects and to discover personalized medicine (AKA, precision medicine) opportunities.
GSK (NYSE:GSK), headquartered in the UK but with a large presence in the US, researches and develops pharmaceutical medicines, vaccines, and other consumer health products.
Owlstone Medical, a diagnostic company, is developing a breathalyzer for disease and says it is on a mission to save 100,000 lives and $1.5 billion in healthcare costs. Dark Daily previously reported on Owlstone Medical’s Breath Biopsy platform. The Cambridge, England-based company has raised significant funding ($23.5 million) and already garnered credible cancer trial collaborators including the UK’s National Health Service (NHS).
Now, Owlstone Medical has brought its breath analysis technology to bear on chronic disease outside of cancer diagnostics development. A pharmaporum article called Owlstone’s Medical’s work with GSK an “additional boost of confidence” in the company’s technology, as well as a means for revenue.
Billy Boyle, co-founder and Chief Executive Officer, Owlstone Medical (above), shown with the company’s ReCIVA Breath Sampler device. This will be used by GSK in its Phase II respiratory disease clinical trial of danirixin to “capture VOC biomarkers in breath samples.” (Photo copyright: Business Weekly UK.)
GSK Studying Future Treatments for Respiratory Diseases
COPD affects about 700 million people worldwide, an increase of about 65% since 1990, GSK pointed out. In September 2017, GSK presented respiratory disease data and its pipeline medications at the European Respiratory Society in Milan, Italy. Included was information on danirixin (an oral CXCR2 antagonist), which is part of the company’s focus on COPD disease modification, according to a GSK news release.
“Each of our studies sets the bar for our future research and innovation,” noted Neil Barnes, MA Cantab, FRCP, FCCP(Hon), Vice President, Global Franchise Medical Head, GSK Respiratory, in the GSK press release.
Clinical Trial Aimed at Identifying the ‘Right’ Patients
With Owlstone Medical’s breathalyzer, GSK plans to explore how volatile organic compounds (VOCs) can help identify patients who will benefit most from the company’s medications, as well as evaluate Danirixin’s effects. A critical element of personalized medicine.
“It’s part of our efforts to identify the right patient for the right treatment,” said Ruth Tal-Singer, PhD, GSK’s Vice President of Medicine Development Leader and Senior Fellow, Respiratory Research and Development, in the Owlstone Medical news release.
VOCs in breath will be captured in a non-invasive way from patients who wear Owlstone Medical’s ReCIVA Breath Sampler, which, according to Owlstone Medical, has CE-mark clearance, a certification noting conformity with European health and safety standards. The VOCs breath samples will then be sent to Owlstone Medical’s lab for high-sensitivity analysis.
“Non-invasive Breath Biopsy can establish a role in precision medicine applications such as patient stratification and monitoring treatment response,” said Billy Boyle, Owlstone Medical’s co-Founder and Chief Executive Officer.
VOC Biomarkers in Respiratory Disease
VOC profiles can be characteristic of COPD as well as other respiratory diseases including asthma, tuberculosis, and cystic fibrosis, reported Science/Business.
According to Owlstone Medical’s Website, VOCs are gaseous molecules produced by the human body’s metabolism that are suitable for Breath Biopsy. Their research suggests that exhaled breath reflects molecular processes responsible for chronic inflammation. Thus, VOCs captured through Breath Biopsy offer insight into respiratory disease biomarkers.
Breath also includes VOCs that originate from circulation, which can provide information on a patient’s response to medications.
How the Breath Biopsy Platform Works
Owlstone Medical’s platform relies on its patented Field Asymmetric Ion Mobility Spectrometry (FAIMS) technology, which “has the ability to rapidly monitor a broad range of VOC biomarkers from breath, urine and other bodily fluids with high sensitivity and selectivity,” according to the company’s website. During the process:
- Gases are exchanged between circulating blood and inhaled fresh air in the lungs;
- VOC biomarkers pass from the circulation system into the lungs along with oxygen, carbon dioxide, and other gases;
- Exhaled breath contains exiting biomarkers.
It takes about a minute for blood to flow around the body. So, a breath sample during that time makes possible collection and analysis of VOC biomarkers from any part of the body touched by the circulatory system.
The medical analysis is enabled by software in the Owlstone Medical lab, Boyle told the Cambridge Independent.
“There’s an analogy with blood prints—you get the blood and can look for different diseases, and we’ve developed core hardware and technology to analyze the breath sample,” he said.
Another Breath Sample Device
The ReCIVA Breath Sampler is not the only breathalyzer focused on multiple diseases. Dark Daily reported on research conducted by Technion, Israel’s Institute of Technology, into a breath analyzer that can detect up to 17 cancers, and inflammatory and neurological diseases.
But Owlstone Medical stands out due, in part, to its noteworthy partners: the UK’s National Health Service, as well as the:
And now the company can add collaboration with GSK to its progress. Though some question the reliability of breath tests as biomarkers in the areas of sensitivity and specificity required for cancer diagnosis, Owlstone Medical appears to have the wherewithal to handle those hurdles. It is a diagnostics company that many pathologists and medical laboratory professionals may find worth watching.
—Donna Marie Pocius
Related Information:
Owlstone Medical’s Breath Biopsy Platform Integrated into GSK’s Phase II Respiratory Disease Clinical Trial
GSK Utilizes Owlstone Disease Breathalyser for Key Clinical Trials
GSK Presents Respiratory Data from Pipeline to Clinical Practice at ERS
GSK Boosts Medtech First Owlstone with Use of Breath Biopsy in Respiratory Trial
Glaxo to Stratify COPD Trial Using Breath Biopsy Device
Billy Boyle of Owlstone Medical on the Inspiration Behind His Mission to Save 100,000 From Dying of Cancer
Owlstone Medical and UK’s NHS Study Whether Breath Contains Useful Biomarkers
Breath Based Biomarker Detection: Informing Drug Development and Future Treatment Regimes
Clinical Laboratories Could Soon Diagnose 17 Diseases with a Single Breath Analyzer Test from Israel’s Institute of Technology
Feb 6, 2017 | Laboratory Hiring & Human Resources, Laboratory Pathology, Laboratory Testing
As chronic disease and aging populations strain the UK’s medical systems, staffing shortages at pathology laboratories contribute to lengthening delays of critical diagnostic services
In the United Kingdom (UK), pathologists and other physicians are going public with their concerns that a growing shortage of pathologists and medical laboratory scientists will soon contribute to delays in performing the lab tests needed to diagnose patients—particularly those with cancer—and identify which therapies will work best for them.
Thanks to vast improvements to both medical laboratory capabilities and treatment options, the cancer survival rate in the UK doubled over the past four decades. However, early diagnosis is a critical component to a successful outcome. As further strain is placed on medical laboratories and diagnostic providers, wait times continue to increase beyond the thresholds created by the UK’s National Health Service (NHS).
Worsening an already dire situation, a November 2016 report from Cancer Research UK, “Testing Times to Come? An Evaluation of Pathology Capacity Across the UK,” predicts a critical shortage in laboratory staffing within the next decade. Data on Provider-based Cancer Waiting Times for August 2016 from National Health Service England shows that 17.2% of patients with an urgent referral for suspected cancer fail to start treatment within two months of the referral. (more…)
Dec 30, 2016 | Compliance, Legal, and Malpractice, Laboratory News, Laboratory Operations, Laboratory Pathology, Managed Care Contracts & Payer Reimbursement
In this second installment of a two-part briefing, the impact of the Affordable Care Act on healthcare spending by businesses and consumers during the past eight years is assessed
No single piece of legislation during the Obama Administration generated more controversy than the Affordable Care Act (ACA), which became law in 2010. It was touted by proponents within and without the administration as the needed solution to the nation’s healthcare problems.
The two biggest problems with healthcare in the United States are probably the sustained year-over-year growth in total healthcare spending and the large number of Americans who lack adequate health insurance. At the time that the ACA was signed into law by President Obama, there were assurances that this law would help solve both problems.
Thus, at the end of the Obama Administration’s eight years in office, both academic experts and journalists are writing their assessment about how the ACA has changed healthcare in the United States. This is a high-interest subject for medical laboratories and pathology groups, hospitals and health systems, and physicians. (more…)
Jun 20, 2016 | Instruments & Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
IBM’s Watson continues to seek a role as a cognitive computing tool of choice for physicians and pathologists in need of evidence-based clinical patient data
Remember IBM’s Watson? It’s been five years since Watson beat human contestants on Jeopardy. Since then, IBM has hoped Watson could be used in healthcare. To that end, some oncologists are exploring the use of Watson in cancer care. This could have implications for anatomic pathologists if oncologists developed a way to use Watson in the diagnosing cancers and identifying appropriate therapies for those cancers.
In 2011, IBM’s Watson supercomputer defeated human contestants for a charity prize during the television show Jeopardy. Just days later, Dark Daily reported on IBM’s goal for Watson to play a major role in helping physicians diagnose and treat disease. Since then, IBM has been exploring ways to commercialize Watson’s cognitive computing platform through partnerships with some of the healthcare industry’s biggest brands. (more…)
