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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)


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 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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Flow cytometry (FC) is a powerful method for counting single cells and measuring their molecular components. There is increasing interest in applying flow cytometry to the analysis of extracellular vesicles (EV), but EVs are orders of magnitude smaller than the cells for which FC instruments and protocols were originally designed. To catalyze the development of new instruments and assays for EV flow cytometry, three scientific societies came together to form the EV Flow Cytometry Working Group (evflowcytometry.org):

  • ISEV, the International Society of Extracellular Vesicles
  • ISAC, the International Society for Advancement of Cytometry, and
  • ISTH, the International Society for Thrombosis and Haemostasis.

The working group first performed two standardization studies, distributing standards and samples to EV-FC laboratories worldwide to enable an objective comparison of methods, instruments, controls, and analytical tools. Those initial studies led to the realization that a standard framework for reporting experimental results is essential.

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Illinois researchers developed a method to detect microRNA cancer markers with single-molecule resolution, a technique that could be used for liquid biopsies.

From left: Taylor Canady, postdoctoral scholar; Andrew Smith, professor of bioengineering; Nantao Li, graduate student; Lucas Smith, postdoctoral scholar; and Brian Cunningham – professor of Electrical and Computer Engineering; director of Micro and Nanotechnology Laboratory.
Photo by L. Brian Stauffer

Thanks to the University of Illinois News Bureau for allowing us to share this article here.

CHAMPAIGN, Ill. — A fast, inexpensive yet sensitive technique to detect cancer markers is bringing researchers closer to a liquid biopsy – a test using a small sample of blood or serum to detect cancer, rather than the invasive tissue sampling routinely used for diagnosis.

Researchers at the University of Illinois developed a method to capture and count cancer-associated microRNAs, or tiny bits of messenger molecules that are exuded from cells and can be detected in blood or serum, with single-molecule resolution. The team published its results in the Proceedings of the National Academy of Science.

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Thanks to Eileen Leahy from Elsevier and Chhavi Chauhan, Director of Scientific Outreach for the Journal of Molecular Diagnostics, for sharing this post here.

A novel non-invasive technique may detect human papilloma virus-16, the strain associated with oropharyngeal cancer, in saliva samples, reports The Journal of Molecular Diagnostics.

Philadelphia, December 13, 2019 – Unfortunately, cancers that occur in the back of the mouth and upper throat are often not diagnosed until they become advanced, partly because their location makes them difficult to see during routine clinical exams. A report in The Journal of Molecular Diagnostics, published by Elsevier, describes the use of acoustofluidics, a new non-invasive method that analyzes saliva for the presence of human papilloma virus (HPV)-16, the pathogenic strain associated with oropharyngeal cancers (OPCs). This novel technique detected OPC in whole saliva in 40 percent of patients tested and 80 percent of co published by Elsevier, describes the use of acoustofluidics, a new non-invasive method that analyzes saliva for the presence of human papilloma virus (HPV)-16, the pathogenic strain associated with oropharyngeal cancers (OPCs). This novel technique detected OPC in whole saliva in 40 percent of patients tested and 80 percent of confirmed OPC patients.

“OPC has an approximate incidence of 115,000 cases per year worldwide and is one of the fastest-rising cancers in Western countries due to increasing HPV-related incidence, especially in younger patients. It is paramount that surveillance methods are developed to improve early detection and outcomes,” explained co-lead investigator Tony Jun Huang, PhD, Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.

“Considering these factors, the successful detection of HPV from salivary exosomes isolated by our acoustofluidic platform offers distinct advantages, including early detection, risk assessment, and screening,” added Dr. Huang. This technique may also help physicians predict which patients will respond well to radiation therapy or achieve longer progression-free survival.

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