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From AAAS Science News on COVID19: New CRISPR based diagnostic may shorten testing time to 5 minutes

Reporter: Stephen J. Williams, Ph.D.

 

 

 

 

 

 

 

 

 

A new CRISPR-based diagnostic could shorten wait times for coronavirus tests.

 

 

New test detects coronavirus in just 5 minutes

By Robert F. ServiceOct. 8, 2020 , 3:45 PM

Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

 

Researchers have used CRISPR gene-editing technology to come up with a test that detects the pandemic coronavirus in just 5 minutes. The diagnostic doesn’t require expensive lab equipment to run and could potentially be deployed at doctor’s offices, schools, and office buildings.

“It looks like they have a really rock-solid test,” says Max Wilson, a molecular biologist at the University of California (UC), Santa Barbara. “It’s really quite elegant.”

CRISPR diagnostics are just one way researchers are trying to speed coronavirus testing. The new test is the fastest CRISPR-based diagnostic yet. In May, for example, two teams reported creating CRISPR-based coronavirus tests that could detect the virus in about an hour, much faster than the 24 hours needed for conventional coronavirus diagnostic tests.CRISPR tests work by identifying a sequence of RNA—about 20 RNA bases long—that is unique to SARS-CoV-2. They do so by creating a “guide” RNA that is complementary to the target RNA sequence and, thus, will bind to it in solution. When the guide binds to its target, the CRISPR tool’s Cas13 “scissors” enzyme turns on and cuts apart any nearby single-stranded RNA. These cuts release a separately introduced fluorescent particle in the test solution. When the sample is then hit with a burst of laser light, the released fluorescent particles light up, signaling the presence of the virus. These initial CRISPR tests, however, required researchers to first amplify any potential viral RNA before running it through the diagnostic to increase their odds of spotting a signal. That added complexity, cost, and time, and put a strain on scarce chemical reagents. Now, researchers led by Jennifer Doudna, who won a share of this year’s Nobel Prize in Chemistry yesterday for her co-discovery of CRISPR, report creating a novel CRISPR diagnostic that doesn’t amplify coronavirus RNA. Instead, Doudna and her colleagues spent months testing hundreds of guide RNAs to find multiple guides that work in tandem to increase the sensitivity of the test.

In a new preprint, the researchers report that with a single guide RNA, they could detect as few as 100,000 viruses per microliter of solution. And if they add a second guide RNA, they can detect as few as 100 viruses per microliter.

That’s still not as good as the conventional coronavirus diagnostic setup, which uses expensive lab-based machines to track the virus down to one virus per microliter, says Melanie Ott, a virologist at UC San Francisco who helped lead the project with Doudna. However, she says, the new setup was able to accurately identify a batch of five positive clinical samples with perfect accuracy in just 5 minutes per test, whereas the standard test can take 1 day or more to return results.

The new test has another key advantage, Wilson says: quantifying a sample’s amount of virus. When standard coronavirus tests amplify the virus’ genetic material in order to detect it, this changes the amount of genetic material present—and thus wipes out any chance of precisely quantifying just how much virus is in the sample.

By contrast, Ott’s and Doudna’s team found that the strength of the fluorescent signal was proportional to the amount of virus in their sample. That revealed not just whether a sample was positive, but also how much virus a patient had. That information can help doctors tailor treatment decisions to each patient’s condition, Wilson says.

Doudna and Ott say they and their colleagues are now working to validate their test setup and are looking into how to commercialize it.

Posted in:

doi:10.1126/science.abf1752

Robert F. Service

Bob is a news reporter for Science in Portland, Oregon, covering chemistry, materials science, and energy stories.

 

Source: https://www.sciencemag.org/news/2020/10/new-test-detects-coronavirus-just-5-minutes

Other articles on CRISPR and COVID19 can be found on our Coronavirus Portal and the following articles:

The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier & Jennifer A. Doudna
The University of California has a proud legacy of winning Nobel Prizes, 68 faculty and staff have been awarded 69 Nobel Prizes.
Toaster Sized Machine Detects COVID-19
Study with important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection

The University of California has a proud legacy of winning Nobel Prizes, 68 faculty and staff have been awarded 69 Nobel Prizes.

Reporter: Aviva Lev-Ari, PhD, RN

PREVIOUS PRIZE WINNERS

The University of California has a proud legacy of winning Nobel Prizes that stretches all the way back to 1939, when Ernest O. Lawrence was awarded the prize in physics for his invention of the cyclotron. In the years since, dozens of other University of California faculty and staff have been awarded this highest international honor for their contributions in medicine, economics, physics and more.

Today, 68 faculty and staff have been awarded 69 Nobel Prizes.

View as grid

Name

Campus affiliation

Field of study

Year of award

  • Jennifer Doudna

    UC Berkeley

    Chemistry

    2020

  • Andrea Ghez

    UCLA

    Physics

    2020

  • Reinhard Genzel

    UC Berkeley

    Physics

    2020

  • Randy Schekman

    UC Berkeley

    Physiology or medicine

    2013

  • Lloyd Shapley

    UCLA

    Economics

    2012

  • Shinya Yamanaka

    UC San Francisco

    Physiology or medicine

    2012

  • Saul Perlmutter

    UC Berkeley/Berkeley Lab

    Physics

    2011

  • Elizabeth Blackburn

    UC San Francisco

    Physiology or medicine

    2009

  • Oliver E. Williamson

    UC Berkeley

    Economics

    2009

  • Roger Y. Tsien

    UC San Diego

    Chemistry

    2008

  • George Smoot

    UC Berkeley/Berkeley Lab

    Physics

    2006

  • Richard R. Schrock

    UC Riverside

    Chemistry

    2005

  • David Gross

    UC Santa Barbara

    Physics

    2004

  • Finn E. Kydland

    UC Santa Barbara

    Economic sciences

    2004

  • Irwin Rose

    UC Irvine

    Chemistry

    2004

  • Robert F. Engle

    UC San Diego

    Economic sciences

    2003

  • Clive Granger

    UC San Diego

    Economic sciences

    2003

  • Sydney Brenner

    UC San Diego

    Physiology or medicine

    2002

  • George Akerlof

    UC Berkeley

    Economic sciences

    2001

  • Alan J. Heeger

    UC Santa Barbara

    Chemistry

    2000

  • Herbert Kroemer

    UC Santa Barbara

    Physics

    2000

  • Daniel McFadden

    UC Berkeley

    Economic sciences

    2000

  • Louis J. Ignarro

    UCLA

    Physiology or medicine

    1998

  • Walter Kohn

    UC Santa Barbara

    Chemistry

    1998

  • Robert B. Laughlin

    UC Livermore Lab

    Physics

    1998

  • Paul D. Boyer

    UCLA

    Chemistry

    1997

  • Steven Chu

    UC Berkeley/Berkeley Lab

    Physics

    1997

  • Stanley B. Prusiner

    UC San Francisco

    Physiology or medicine

    1997

  • Paul Crutzen

    UC San Diego

    Chemistry

    1995

  • Mario J. Molina

    UC San Diego

    Chemistry

    1995

  • Frederick Reines

    UC Irvine

    Physics

    1995

  • F. Sherwood Rowland

    UC Irvine

    Chemistry

    1995

  • John Harsanyi

    UC Berkeley

    Economic sciences

    1994

  • Harry Markowitz

    UC San Diego

    Economic sciences

    1990

  • J. Michael Bishop

    UC San Francisco

    Physiology or medicine

    1989

  • Harold E. Varmus

    UC San Francisco

    Physiology or medicine

    1989

  • Donald J. Cram

    UCLA

    Chemistry

    1987

  • Yuan T. Lee

    UC Berkeley/Berkeley Lab

    Chemistry

    1986

  • Gerard Debreu

    UC Berkeley

    Economic sciences

    1983

  • Czeslaw Milosz

    UC Berkeley

    Literature

    1980

  • Roger Guillemin

    UC San Diego

    Physiology or medicine

    1977

  • Renato Dulbecco

    UC San Diego

    Physiology or medicine

    1975

  • George Emil Palade

    UC San Diego

    Physiology or medicine

    1974

  • John Robert Schrieffer

    UC Santa Barbara

    Physics

    1972

  • Hannes Alfven

    UC San Diego

    Physics

    1970

  • Luis Walter Alvarez

    UC Berkeley/Berkeley Lab

    Physics

    1968

  • Robert W. Holley

    UC San Diego

    Physiology or medicine

    1968

  • Julian Schwinger

    UCLA

    Physics

    1965

  • Charles H. Townes

    UC Berkeley

    Physics

    1964

  • Maria Goeppert-Mayer

    UC San Diego

    Physics

    1963

  • Francis Crick

    UC San Diego

    Physiology or medicine

    1962

  • Melvin Calvin

    UC Berkeley/Berkeley Lab

    Chemistry

    1961

  • Donald A. Glaser

    UC Berkeley/Berkeley Lab

    Physics

    1960

  • Willard Libby

    UCLA

    Chemistry

    1960

  • Owen Chamberlain

    UC Berkeley/Berkeley Lab

    Physics

    1959

  • Emilio Segrè

    UC Berkeley/Berkeley Lab

    Chemistry

    1959

  • Linus Pauling

    UC San Diego

    Chemistry, Peace

    1954, 1962

  • Edwin McMillan

    UC Berkeley/Berkeley Lab

    Chemistry

    1951

  • Glenn T. Seaborg

    UC Berkeley/Berkeley Lab

    Chemistry

    1951

  • William Giauque

    UC Berkeley

    Chemistry

    1949

  • John Howard Northrop

    UC Berkeley

    Chemistry

    1946

  • Wendell Meredith Stanley

    UC Berkeley

    Chemistry

    1946

  • Ernest Lawrence

    UC Berkeley/Berkeley Lab

    Physics

    1939

  • Harold Urey

    UC San Diego

    Chemistry

    1934

HOW UC NOBEL LAUREATES ARE COUNTED

Our list of Nobel Prize winners includes University of California faculty and staff who were affiliated with UC when they received their award. It also includes faculty and staff who joined UC after receiving their Nobel Prize. And although we are immensely proud of the many UC alumni who have gone on to receive Nobel Prizes, they are not counted here. Nor are visiting scholars or others who had short-term assignments with UC. Finally, our Nobelist list is a “lifetime” list and includes those living, retired or deceased.

SOURCE

https://nobel.universityofcalifornia.edu/


Tiny biologic drug to fight COVID-19 show promise in animal models

Reporter : Irina Robu, PhD

A research team at University of Pittsburg School of Medicine identified an antibody component that is 10 times smaller than a full-sized antibody. Their research published in Cell, indicates that the drug, Ab8 based on it is effective in mice and hamsters. The research was started by screening a library of about 100 billion antibody fragments to identify candidates that bound tightly to the spike protein on SARS-CoV-2’s surface, which the virus uses to enter and infect human cells.

A typical antibody consists of two heavy chains and two light chains. The chosen molecule is the variable domain of the heavy chain of an immunoglobulin, which is a type of antibody. The heavy chain variable domain is essential for binding with an antigen. Ab8 was created by fusing the variable, heavy chain domain with part of the immunoglobulin tail region, giving it immune functions but doing so with a molecule that’s about half the size of a full immunoglobulin.

The smaller size of the antibody can improve the therapeutic efficacy for infectious diseases and can be delivered through inhalation. Their research showed that Ab8 completely neutralized SARS-CoV-2 in lab dishes. The drug developed showed that inhibited the virus in lung tissue in animal body even at the lowest dose 2 mg/kg as compared to untreated controls.

The research team is looking to determine the drug effect in hamsters, which were reported to have better clinical signatures of COVID-19. And the hamsters that got the drug display less severe pneumonia that did the control animals. Drugs with alternative administration routers could provide additions to the first wave of COVID-19 therapies and vaccines.

What is more important, Ab8 does not appear to bind to human cells which is a good sign that it won’t have negative side effects.

SOURCE

https://www.fiercebiotech.com/research/small-sized-biologic-against-covid-19-shows-promise-animal-models

 

 


Llama inspired “AeroNabs” to strangle COVID-19 with an inhaler 

Reporter : Irina Robu, PhD

Llama and other camelids fight off pathogens like viruses with tiny antibodies called nanobodies. A USCF team used protein engineering to make a synthetic nanobody that prevents the spike protein on the surface of SARS-CoV-2 from binding to healthy cells and infecting them. The team indicates promising preclinical results for aerosol formulation and can be used as a self-administered form of protein against the virus.

According to the UCSF team, an aerosolized form of nanobody exhibit SARS-CoV-2 incapable of binding to the ACE2 receptor on healthy cells that line airways. The synthetic nanobody stays functional after it was freeze-dried, exposed to heat and aerosolized.

The researchers ongoing screening a library of synthetic nanobodies, ultimately landing on 21 that banned the spike-ACE2 interaction. The scientists decided that in order to be truly efficient, a nanobody based treatment with interact with all three of the receptor binding domains on the spike protein that attaches to ACE2.  Their solution was to engineer a molecular chain that connects three nanobodies together, which would ensure that when one of the nanobodies attached to RBD, the others would link to the two remaining RBD. This molecular chain resulted in a drug candidate proved to be 200,000 times more potent than a single antibody.

At the same time, ExeVir Bio is also developing an aerosolized COVID-19 treatment inspired by llamas and is currently trying to advance its candidate into clinical trials by the end of the year. Their main candidate, VHH-72Fc was considered to bind to an epitope that is found both in SARS-CoV-2 and SARS-CoV. Yet, the llama inspired treatments are still behind antibody efforts like that of Regeneron.

Even though, there are multiple vaccines in development, researchers at UCSF believe that AeroNabs can be used as a sort of personal protective equipment until vaccines become available. The same researchers are planning human trials and are in discussion with partners who can provide manufacturing and distribution backing.

SOURCE

https://www.fiercebiotech.com/research/ucsf-engineers-develop-llama-inspired-aeronabs-to-strangle-covid-19-inhaler



AI-controlled sensors could save lives in smart hospitals and homes

Reporter: Irina Robu, PhD

Arnold Milstein, professor of medicine and director of Stanford’s Clinical Excellence Research Center along with Fei-Fei Li, computer science professor and graduate student Albert Haque  believe that having the ability to build technologies into the physical spaces where health care is delivered minimize the rate of fatal errors that occur lately due to sheer volumes of patients and complexity of their care. Even though, the technology is a very promising, it also raises legal and regulatory issues as well as privacy concerns.

They believe that the AI can alert clinicians and patient visitors when they fail to sanitize their hands before entering hospital room for example. Also, AI tools can be built into smart homes where the technology can monitor the frail elderly for behavioral clues of a health crises and can let in-home caregivers, remotely located clinicians and patients to make life saving interventions.

Li and Milstein co-direct the 8-year-old Stanford Partnership in AI-Assisted Care (PAC), one of a growing number of centers, including those at Johns Hopkins University and the University of Toronto, where technologists and clinicians have teamed up to develop ambient intelligence technologies to help health care providers manage patient volumes, roughly 24 million Americans required an overnight hospital stay in 2018.

Haque, who compiled the 170 scientific papers cited in the Nature article, the availability of infrared sensors that are inexpensive enough to build into high-risk care-giving environments, and the rise of machine learning systems as a way to use sensor input to train specialized AI applications in health care.

The infrared technologies are of two types. The first is active infrared, such as the invisible light beams used by TV remote controls. Nonetheless as an alternative of simply beaming invisible light in one direction, like a TV remote, new active infrared systems use AI to compute the time it takes the invisible rays to bounce back to the source, like a light-based form of radar that maps the 3D outlines of a person or object.

These alert systems are being confirmed to see if they can reduce the number of ICU patients who get nosocomial infections due to failure of other people in the hospital to fully observe to infection prevention protocols.

The second type of infrared technology are passive detectors, that allow night vision goggles to generate thermal images from the infrared rays generated by body heat. In a hospital setting, a thermal sensor above an ICU bed would allow the governing AI to sense twitching beneath the sheets, and alert clinical team members to forthcoming health crises without continuously going from room to room.

Constant monitoring by ambient intelligence systems in a home environment could also be used to detect clues of serious illness or potential accidents, and alert caregivers to make timely interventions. . Researchers are still developing activity recognition algorithms that can examine through infrared sensing data to detect variations in habitual behaviors, and benefit caregivers get a more holistic view of patient health.

SOURCE

https://engineering.stanford.edu/magazine/article/ai-controlled-sensors-could-save-lives-smart-hospitals-and-homes

 


Noninvasive blood test can detect cancer 4 years before conventional diagnosis

Reporter : Irina Robu, PhD

Several international researchers at  Fudan University and at Singlera Genomics have developed a noninvasive blood test, PanSeer that can detect whether a patient with five common type of cancers such as stomach, esophageal, colorectal, lung and liver cancer; four years before the condition can be diagnosed by the current methods. Early detection is significant for the reason that the survival of cancer patients increases when the disease is identified at early stages, as the tumor can be surgically removed or treated with suitable drugs. Yet, only a partial number of early screening tests exist for a few cancer types.

The blood test detected cancer in 91 percent of samples from individuals who have been asymptomatic when the samples were collected, but only diagnosed with cancer one to four years later. It was found that the test can accurately detect cancer in 88 percent from samples of 113 patience who were diagnosed. The blood test also detects cancer free samples 95 percent of the time.

What is clear is that the study is unique, in that the scientists had access to blood samples from patients who were asymptomatic but not diagnosed yet. This permitted the researchers to design a test that can find a cancer marker much earlier than conventional diagnosis. The sample were collected as part of 10-year longitudinal study started in 2007 by Fudan University in China.

The researchers highlight that the PanSeer assay is improbable to predict which patients will later go on to develop cancer. As a substitute, it is most possible identifying patients who already have cancerous growths, but continue  to be asymptomatic for current detection methods. The team decided that further large-scale longitudinal studies are needed to confirm the potential of the test for the early detection of cancer in pre-diagnosis individuals.

SOURCE

https://www.universityofcalifornia.edu/news/non-invasive-blood-test-can-detect-cancer-4-years-conventional-diagnosis-methods?utm_source=fiat-lux


FDA Authorizes Convalescent Plasma for COVID-19 Patients

Reporter: Irina Robu, PhD

The U.S. Food and Drug Administration authorized convalescent plasma therapy in August 2020 for people with coronavirus disease 2019. The convalescent plasma shows promising efficacy in hospitalized patients with COVID-19 and the benefits outweighs the risk  and FDA gave emergency use authorization. The approval is not  for any particular convalescent plasma product, but for preparation collected by FDA registered blood establishments from individuals whose plasma contains anti-SARS-CoV-2 antibodies, and who meet all donor eligibility requirements.

What exactly is convalescent plasma ? It is blood donated from patients who have recovered from COVID-19 has antibodies to the virus that causes it. The donated blood is processed by removing blood cells, leaving behind plasma and antibodies, which can be given to people with COVID-19 to boost their ability to fight the virus. According to FDA, COVID-19 covalescent plasma with high antibody titer can be effective in reducing mortality in hospitalized patients, but low antibody titer can be used based on health care provider discretion.  FDA also indicated that COVID-19 convalescent plasma may be effective in lessening the severity or shortening the length of COVID-19 illness in some hospitalized patients.

To confirm the results, the FDA recommended randomized trialsas COVID-19 convalescent plasma does not yet describe a new standard of care based on the current available evidence.

SOURCE

https://www.medpagetoday.com/infectiousdisease/covid19/88225?xid=NL_breakingnewsalert_2020-08-23


Bioresorbable Stent Clinical Trials with New Esprit Below-the-knee Scaffold

Reporter: Irina Robu, PhD

Abbott announced on September 3, 2020, the beginning of the LIFE-BTK clinical trial to evaluate effectiveness and safety of  the Esprit BTK Everolimus Eluting Resorbable Scaffold System. The Esprit BTK System consists of a thin strutted scaffold made of poly-L-lactide, a semi-crystalline bioresorbable polymer engineered to resist vessel recoil and provide a platform for drug delivery. The scaffold is coated with poly-D, L-lactide (PDLLA) and the cytostatic drug, everolimus.

This trial is the first Investigational Device Exemption in the US to assess a fully bioresorbable stent to treat blocked arteries below the knees, also known as critical limb ischemia in people battling advanced stages of peripheral artery disease. For people with CLI, blocked vessels weaken blood flow to the lower extremities, which can lead to severe pain, wounds, and in severe cases, limb amputation.

At this time, the standard of care for patients battling critical limb ischemia is balloon angioplasty, which depend on on a small balloon delivered via a catheter to the blockage to compress it against the arterial wall, opening the vessel and restoring blood flow. Yet, blockages treated only with balloon angioplasty have poor short- and long-term results, and in many cases the vessels become blocked again, lacking additional treatment.

Patients treated with balloon angioplasty often require several procedures on treated arteries, and  a drug eluting resorbable device is if at all possible suited to provide mechanical support, decrease the chance of the vessel re-narrowing and then slowly disappear over time. At this time, there are no drug eluding stents, drug coated balloons or bare metal stents approved for use below the knee. Since, there is a limited number of options for stents below the knee, the FDA has granted Esprit BTK breakthrough device designation, which simplifies review and pre-market approval timelines.

According to Abbott, Espirit BTK System is not a permanent implant, but it does provide support to an artery right after a balloon angioplasty, stopping the vessel from reclosing. As soon as it is implanted, the scaffold distributes a drug over a few months that encourages healing and keeps the artery open. The scaffold is naturally resorbed into the body over time, like dissolving sutures, and eventually leaves only a healed artery behind.

The LIFE-BTK trial is the first Investigational Device Exemption trial in the U.S. to evaluate a fully dissoluble device to treat critical limb ischemia in people battling advanced stages of peripheral artery disease (PAD). The trial will be run by principal investigators Brian DeRubertis, M.D. (vascular surgeon, UCLA), Sahil Parikh M.D., (interventional cardiologist, New York-Presbyterian/Columbia University Irving Medical Center.

SOURCE

https://www.dicardiology.com/article/abbott-restarts-bioresorbable-stent-clinical-trials-new-esprit-below-knee-scaffold

 

 

 


Artificial pancreas effectively controls type 1 diabetes in children age 6 and up

Reporter: Irina Robu, PhD

A new trial funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institute of Health created a clinical trial at four pediatric diabetes centers in the US of a new artificial pancreas system, which monitors and regulates blood glucose levels automatically. The artificial pancreas technology, the Control-IQ system has an insulin pump programmed with advanced control algorithms based on a mathematical model using the person’s glucose monitoring information to automatically adjust the insulin dose, and it was originally developed at University of Virginia (UVA), Charlottesville with funding support from NIDDK.

The artificial pancreas closed-loop control is all in one diabetes management system which monitors and tracks blood glucose levels using a continuous glucose monitor and at the same time delivers the insulin when needed via an insulin pump. The system is not only useful in children age 6 and up, but it also replaces reliance on testing by fingerstick or delivering insulin via injection multiple times a day.

The study contains 101 children between ages of 6 and 13 and the children are assigned either to the control or experimental group. The control group uses a standard injection method and separate insulin pump and the experimental uses the artificial pancreas system. Data was conducted every week for four months, while the participants continue on daily lives.

The results of the study showed that using an artificial pancreas system has a 7% improvement in keeping blood glucose in range during the daytime, and a 26% improvement in nighttime control compared to the control group. However, night time control group is important in people with type 1 diabetes, since unchecked hypoglycemia can lead to seizure, coma or even death. The artificial pancreas system shows about 11 % improvement to the standard method and it shows that the improvement in blood glucose control is impressive and safer for kids. No severe case of hypoglycemia or diabetic ketoacidosis occurred during the study, only some minor issues with the equipment.

After the clinical trial and based on the data received, Tandem Diabetes Care has received clearance from the U.S. FDA for use of the Control-IQ system in children as young as age 6 years.

SOURCE
https://www.nih.gov/news-events/news-releases/artificial-pancreas-effectively-controls-type-1-diabetes-children-age-6