This blog originated as a press release from The Ohio State University. Thanks to them for allowing us to repost it here.

Inserting genetic material into the body to treat diseases caused by gene mutations can work, scientists say – but getting those materials to the right place safely is tricky.

Scientists from The Ohio State University have reported in the journal Science Advances that the lipid-based nanoparticles they engineered, carrying two sets of protein-making instructions, showed in animal studies that they have the potential to function as therapies for two genetic disorders.

In one experiment, the payload-containing nanoparticles prompted the production of the missing clotting protein in mice that are models for hemophilia. In another test, the nanoparticles’ cargo reduced the activation level of a gene that, when overactive, interferes with clearance of cholesterol from the bloodstream.

Dr. Yizhou Dong Dr. Yizhou Dong

Each nanoparticle contained an applicable messenger RNA molecule that translates genetic information into functional proteins.

“We demonstrated two applications for lipid-like nanomaterials that effectively deliver their cargo, appropriately biodegrade, and are well-tolerated,” said Yizhou Dong, senior author of the study and associate professor of pharmaceutics and pharmacology at The Ohio State University.

“With this work, we have lowered potential side effects and toxicity and have broadened the therapeutic window. This gives us confidence to pursue studies in larger animal models and future clinical trials.”

This work builds upon a collection of lipid-like spherical compounds that Dong and colleagues had previously developed to deliver messenger RNA. This line of particles was designed to target disorders involving genes that are expressed in the liver.

The team experimented with various structural changes to those particles, effectively adding “tails” of different types of molecules to them, before landing on the structure that made the materials the most stable. The tiny compounds have a big job to do: embarking on a journey through the bloodstream, carrying molecules to the target location, releasing the ideal concentration of messenger RNA cargo at precisely the right time, and safely degrading.

The tests in mice suggested these particles could do just that.

The researchers injected nanoparticles containing messenger RNA holding the instructions to produce a protein called human factor VIII into the bloodstream of normal mice and mouse models for hemophilia. A deficiency of this protein, which enables blood to clot, causes the bleeding disorder. Within 12 hours, the deficient mice produced enough human factor VIII to reach 90 percent of normal activity. A check of the organs of both protein-deficient mice and normal mice showed that the treatment caused no organ damage.

“It can be helpful to think of this as a protein-replacement therapy,” Dong said.

In the second experiment, nanomaterials were loaded with two types of instructions: messenger RNA carrying the genetic code for a DNA base editor, and a guide RNA to make sure the edits occurred in a specific gene in the liver called PCSK9. Dozens of mutations that increase this gene’s activity are known to cause high cholesterol by reducing clearance of cholesterol from the bloodstream.

Analyses showed that the treatment resulted in the intended mutation of about 60 percent of the target base pairs in the PCSK9 gene, and determined that only a low dose was needed to produce high editing effect.

Dong credited academic and industry partners for helping advance this work. Co-corresponding authors include Denise Sabatino of Children’s Hospital of Philadelphia and Delai Chen from Boston-based Beam Therapeutics, who provided expertise in hemophilia and DNA base editing, respectively.

Dong and first author Xinfu Zhang are inventors on patent applications filed by Ohio State related to the lipid-like nanoparticles. This technology has been licensed for further clinical development.

This work was supported by the National Institute of General Medical Sciences, the National Heart, Lung and Blood Institute, and a startup fund from Ohio State’s College of Pharmacy.

Additional co-authors are Giang N. Nguyen of Children’s Hospital of Philadelphia; Weiyu Zhao, Chengxiang Zhang, Chunxi Zeng, Jingyue Yan, Shi Du, Xucheng Hou, Wenqing Li, Justin Jiang, Binbin Deng and David McComb of Ohio State; and Robert Dorkin, Aalok Shah, Luis Barrera, Francine Gregoire and Manmohan Singh of Beam Therapeutics.

Reference
Zhang X et al. Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing. (2020) Sci Adv 6:eabc2315. doi: 10.1126/sciadv.abc2315. PMID: 32937374.

The ASEMV2020 organizing committee would like to congratulate the winners of this year’s Young Investigator Awards. There were three speaker awards, for talks by a Young Investigator, a postdoctoral scholar, and a Ph.D. candidate. There are also two poster winners.

Speaker Awards


Moran Amit

Assistant Professor
Department of Head and Neck Surgery – Research
Division of Surgery
University of Texas MD Anderson Cancer Center

for work on the role of p53 and axonogenesis in cancer



Frederik Verweij

Post-Doctoral Fellow
Team van Niel
Institute of Psychiatry and Neuroscience of Paris

for research on EV biology in a zebrafish model system

See Dr. Verweij’s recent #WebEVTalk outlining the zebrafish model system for tracking EVs.




Hannah McMillan

Ph.D. Candidate
Kuehn Lab
Department of Molecular Genetics and Microbiology
Duke University

for studies on the protective immune pathways in plants elicited by bacterial OMVs


Poster Awards


Killian O’Brien

Post-Doctoral Fellow
Breakefield Lab
Harvard Medical School &
Massachusetts General Hospital

for research on understanding the intracellular fate of EV-delivered content


Kathleen Lennon
Ph.D. Candidate
Talisman Lab
Irell and Manella Graduate School of Biological Sciences
City of Hope

for work on EV characterization using quantitative Single Molecule Localization Microscopy (qSMLM)


This blog originated as a press release from The Ohio State University. Thanks to them for allowing us to repost it here.

Dr. Raphael Pollock has earned the reputation as one of the world’s best surgical oncologists for patients facing one of the toughest cancers to treat, sarcoma. Frequently these tumors start out in the very deepest recesses of the retroperitoneum, the part of the abdomen where the kidneys, pancreas and inferior vena cava are located.

Dr. Raphael Pollock Dr. Raphael Pollock

Director of The Ohio State University Comprehensive Cancer Center, Pollock’s 30 years of experience in the operating room naturally led him to ponder the steps before surgery, specifically if there were better ways to diagnose or detect sarcomas. In early 2019, he tapped into Ohio State’s scientific breadth and depth to investigate a new diagnostic method based upon research he conducted while at MD Anderson Cancer Center in Houston. He reached out to Shaurya Prakash, associate professor of mechanical and aerospace engineering and an expert in microfluidics.

Currently, there are two predominant options to acquire a diagnostic biopsy of a tumor deep in the abdomen: invasive surgery under general anesthesia; or a method utilizing computed tomography (CT) scans to guide a long needle through the skin to acquire tissue from the mass. Both are expensive and take time to schedule.

“I’ve been interested for a while in the role of exosomes in the spread of cancers,” Pollock said. Exosomes are extracellular vesicles containing constituents—protein, DNA, and RNA—of the cells that secrete them. They can affect function and behavior of other cells with which they interact. Until recently, they were regarded as merely cell waste products without much clinical research relevance.

Dr. Shaurya Prakash Dr. Shaurya Prakash

“We learned that there are a number of things inside the exosomes that interact potentially with cells in the tumor microenvironment,” he added. “Then they circulate in the bloodstream and land in other parts of the body.”

So Pollock asked Prakash if there could be an efficient way of extracting these exosomes from a peripheral blood sample to obtain the contents that might be used to diagnose a tumor deep within the body. The microfluidics expert was intrigued.

“I learned that often by the time sarcomas are diagnosed, the disease state is very advanced,” Prakash said. “The value of isolating these circulating biomarkers is earlier detection. Prognosis is better with earlier detection and diagnosis.”

In the past, Pollock had employed ultracentrifugation to isolate exosomes from blood, but it was arduous and expensive. He and Prakash reviewed the literature and realized there might be several different engineering concepts that could be leveraged to improve the process.

Size-based filtration was first, since exosome size is quite specific. Prakash’s previous water treatment research was useful in developing a microfluidic filtration system. Their second area of focus was targeting a surface marker or protein with monoclonal antibodies to attach, secure and extract the exosomes.

Microfluidic device prototype Microfluidic device prototype

The duo’s prototype microfluidic device integrates size-based separation followed by immunoaffinity-based capture of extracellular vesicles in one process. They also are exploring the use of electrical charge to enhance the exosome filtering.

Prakash and Pollock have submitted two manuscripts—one of which was published recently in the Journal of Microelectromechanical Systems—demonstrating their device is more effective than ultracentrifugation in terms of time, yield, and purity.

The collaboration is just the latest example of an emerging partnership between the College of Engineering and The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.

“These circulating biomarkers are a very small fraction of the overall constituency of blood,” explained Prakash. “The real engineering challenge is extracting that proverbial needle from a haystack. And how do you sort that out and get the right needle.”

Exploded view of microfluidic channels Exploded view of microfluidic channels separated by a nanocapillary array membrane. The dotted line represents the cross-section that was utilized for SEM characterization of the device, as seen inset. Only a portion of captured exosomes may have been connected to the tumor, so capturing as many as possible within a blood sample is critical.

Beyond the manuscripts, the research team is gearing up to submit a proposal. Coincidentally, the National Cancer Institute is now seeking proposals that focus on developing new methodologies to extract exosomes to investigate whether the cargo inside may be applicable as biomarkers for cancer.

“We’re now in a position to really drill down into the engineering concepts of the device,” Pollock said.

He added that while this type of device could be applied to many types of cancers, it is especially advantageous for sarcoma diagnosis.

“After a long operation to remove a confirmed tumor, it is very difficult in scans to differentiate tumor recurrence from post-surgical scarring,” he explained. “But if you can detect something a tumor releases in the bloodstream, that provides you with a higher index of suspicion of what you may be seeing on a scan.

“Instead of relying on repeat scans over months to determine size increase or decrease, we can potentially identify recurrence at a very early point when the total volume of recurrence is small and more amenable to treatment. We’re very excited about the potential.”

Looking ahead, Prakash and Pollock want to build toward a systematic clinical trial. While there is nothing in the prototype device that cannot be used in a clinical trial, Prakash said some optimization would be required.

“It’s been a total partnership,” Pollock said. “None of this would have happened without the mutual interest and opportunities to communicate about possibilities.”

The research team included mechanical and aerospace engineering PhD student Prashanth Mohana Sundaram, and Lucia Casadei, Gonzalo Lopez, Danielle Braggio and Gita Balakirsky from the Comprehensive Cancer Center.

Duke Health This blog originated as a press release from Duke Health. Thanks to them for allowing us to repost it here.

DURHAM, N.C. – A team of Duke Health scientists have identified biomarkers that accurately identify numerous viral infections across the clinical stages of disease, advancing a potential new way to guide treatment, quarantine decisions, and other clinical and public health interventions in the setting of endemic and pandemic infectious diseases.

The blood-based test uses a gene expression assay to correctly predict nine different respiratory viral infections including influenza, enterovirus, adenovirus, and coronaviruses known to cause common colds. It shows the body’s genes responding to a pathogen before symptoms are present.

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This blog originated as a press release from Cedars-Sinai. Thanks to them for allowing us to repost it here.

Analysis of particles shed by tumors points to new, less invasive way to diagnose malignancies

A recent study sheds light on proteins in particles called extracellular vesicles, which are released by tumor cells into the bloodstream and promote the spread of cancer. The findings suggest how a blood test involving these vesicles might be used to diagnose cancer in the future, avoiding the need for invasive surgical biopsies.

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This blog originated as a press release from the University of Sussex. Thanks to them for allowing us to repost it here.

Scientists at the University of Sussex have identified a potential pattern within blood which signals the presence of motor neuron disease; a discovery which could significantly improve diagnosis.

Currently, it can take up to a year for a patient to be diagnosed with amyotrophic lateral sclerosis (ALS), more commonly known as motor neuron disease (MND).

But after comparing blood samples from patients with ALS, those with other motor-related neurological diseases, and healthy patients, researchers were able to identify specific biomarkers which act as a diagnostic signature for the disease.

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This blog originated as a press release from ISGlobal, the Barcelona Institute for Global Health. Thanks to ISGlobal for permission to post it here.

A new study shows that extracellular vesicles from the malaria parasite Plasmodium vivax promote parasite adhesion to spleen cells

Extracellular vesicles (EVs) play a role in the pathogenesis of malaria vivax, according to a study led by researchers from the Barcelona Institute for Global Health (ISGlobal), an institution supported by the ”la Caixa” Foundation, and the Germans Trias i Pujol Research Institute (IGTP). The findings, published in Nature Communications, indicate that EVs from P. vivax patients communicate with spleen fibroblasts promoting the adhesion of parasite-infected red blood cells. These data provide important insights into the pathology of vivax malaria. The study was carried out at the Can Ruti Campus, with the participation of the IGTP Genomics platform, the Nephrology service of the Germans Trias i Pujos Hospital, and researchers from the Irsicaixa AIDS Research Institute.

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With a focus on screening local healthcare workers and first responders, the epidemiological study seeks to understand the prevalence of coronavirus infections in the community. The lab of ERCC2’s Louise Laurent is part of the core research team.

LA JOLLA, CA—A consortium that includes many of San Diego’s top medical and scientific research institutes has launched a large-scale COVID-19 screening effort to better understand the spread and prevalence of the virus in the local community, with an initial focus on evaluating healthcare workers and first responders.

Known as the San Diego Epidemiology and Research for COVID Health (SEARCH) alliance, the cross-institutional collaboration is co-led by scientists and clinical researchers at Rady Children’s Hospital-San Diego, Rady Children’s Institute for Genomic Medicine, Scripps Research, and University of California San Diego.

As part of the SEARCH study, San Diego fire fighters are screened for SARS-CoV-2, the virus that causes COVID-19. .
Credit: Don Boomer

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This blog originated as a press release from Notre Dame News.

As testing for the coronavirus continues throughout the United States, researchers have been closely watching results, particularly reported rates of false negatives.

According to the Radiological Society of North America, a reported 40 to 70 percent of coronavirus tests from throat swab samples returned false negatives at the onset of the epidemic. Given the highly infectious nature of this particular coronavirus, individuals receiving false negative results — told they do not carry the virus when in fact they do — could continue to infect others.

“It is very concerning,” said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at the University of Notre Dame. “In an overcrowded hospital, where there is only room to quarantine the COVID-19 carriers, false negatives would mean some carriers can continue to infect other patients and healthcare workers. This, unfortunately, is also true for other infectious viral diseases such as dengue and malaria, when there is an epidemic. False negatives are usually not an urgent problem, when every symptomatic patient can be quarantined and there are fewer people to infect — until an epidemic overcrowds our hospitals and we have only enough space to sequester the carriers.”

At Notre Dame, Chang’s research lab focuses on the development of new diagnostic and micro/nanofluidic devices that are portable, sensitive and fast. His work includes diagnostics with applications to DNA/RNA sensing. Current coronavirus tests are RNA-based.

Chang said technology his lab developed for other uses could easily be extended to apply to testing for the coronavirus.

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This blog originated as a press release from UCSD News.

Researchers at the University of California San Diego discovered that high blood levels of RNA produced by the PHGDH gene could serve as a biomarker for early detection of Alzheimer’s disease. The work could lead to the development of a blood test to identify individuals who will develop the disease years before they show symptoms.

The team published their findings in Current Biology.

The PHGDH gene produces RNA and proteins that are critical for brain development and function in infants, children, and adolescents. As people get older, the gene typically ramps down its production of these RNAs and proteins. The new study, led by Sheng Zhong, a professor of bioengineering at the UC San Diego Jacobs School of Engineering in collaboration with Dr. Edward Koo, a professor of neuroscience at the UC San Diego School of Medicine, suggests that overproduction of extracellular RNA (exRNA) by the PHGDH gene in the elderly could provide an early warning sign of Alzheimer’s disease.

“Several known changes associated with Alzheimer’s disease usually show up around the time of clinical diagnosis, which is a little too late. We had a hunch that there is a molecular predictor that would show up years before, and that’s what motivated this study,” Zhong said.

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