Tag Archives: RNA

Coronavirus Vaccine: Moderna and Pfizer Final Test Results Imminent

Moderna should have enough data from its late-stage trial to know whether its coronavirus vaccine works in November, CEO Stephane Bancel said Thursday. The company could have enough data by October, but that’s unlikely, Bancel said during an interview on CNBC’s “Squawk Box.

If the infection rate in the country were to slow down in the next weeks, it could potentially be pushed out in a worst-case scenario in December,” he added.

Moderna is one of three drugmakers backed by the U.S. in late-stage testing for a potential vaccine. The other two are companies Pfizer and AstraZeneca.

Moderna‘s experimental vaccine contains genetic material called messenger RNA, or mRNA, which scientists hope provokes the immune system to fight the virus. In July, the company released early-stage data that showed its potential vaccine generated a promising immune response in a small group of patients.

Bancel’s comment came four days after the CEO of Pfizer said its vaccine could be distributed to Americans before the end of the year. CEO Albert Bourla told CBS’ “Face the Nation” that the company should have key data from its late-stage trial for the Food and Drug Administration by the end of October. If the FDA approves the vaccine, the company is prepared to distribute “hundreds of thousands of doses,” he said.

Source: https://www.cnbc.com/

Why RNA Is A Better Measure Of A Patient’s Current Health Than DNA

By harnessing the combined power of NGS, machine learning and the dynamic nature of RNA we’re able to accurately measure the dynamic immune response and capture a more comprehensive picture of what’s happening at the site of the solid tumor. In the beginning, there was RNA – the first genetic molecule.

In the primordial soup of chemicals that represented the beginning of life, ribonucleic acid (RNA) had the early job of storing information, likely with the support of peptides. Today, RNA’s cousin – deoxyribonucleic acid – or DNA, has taken over most of the responsibilities of passing down genetic information from cell-to-cell, generation-to-generation. As a result, most early health technologies were developed to analyze DNA. But, RNA is a powerful force. And its role in storing information, while different from its early years, has no less of an impact on human health and is gaining more mindshare in our industry.

RNA is often considered a messenger molecule, taking the information coded in our DNA and transcribing it into cellular directives that result in downstream biological signals and proteinslevel changes.  And for this reason, RNA is becoming known not only as a drug target but perhaps more importantly, as a barometer of health.

3d illustration of a part of RNA chain from which the deoxyribonucleic acid or DNA is composed

How and why is RNA so useful? First, RNA is labile — changing in both sequence and abundance in response to genetic and epigenetic changes, but also external factors such as disease, therapy, exercise, and more. This is in contrast to DNA, which is generally static, changing little after conception.

Next, RNA is a more accurate snapshot of disease progression. When mutations do occur at the DNA level, these do not always result in downstream biological changes. Often, the body is able to compensate by repairing the mutation or overcome it by using redundancies in the pathway in which the gene resides. By instead evaluating RNA, we get one step closer to understanding the real impact disease is imparting on our body.

Finally, RNA is abundant. In most human cells, while only two copies of DNA are present, hundreds of thousands of mRNA molecules are present,representing more than 10,000 different species of RNA. Because even rare transcripts are present in multiple copies, biological signals can be confidently detected in RNA when the right technology is used.

Source: https://medcitynews.com/

3D Mapping of Coronavirus Genome

The novel coronavirus uses structures within its RNA to infect cells. Scientists have now identified these configurations, generating the most comprehensive atlas to date of SARS-CoV-2’s genome. Although contained in a long, noodle-like molecule, the new coronavirus’s genome looks nothing like wet spaghetti. Instead, it folds into stems, coils, and cloverleafs that evoke molecular origami.

A team led by RNA scientist Anna Marie Pyle has now made the most comprehensive map to date of these genomic structures. In two preprints posted in July 2020 to bioRxiv.org, Pyle’s team mapped structures across the entire RNA genome of the coronavirus SARS-CoV-2, using living cells and computational analyses.

SARS-CoV-2 relies on its unique RNA structures to infect people and cause the illness COVID-19. But these structures’ contribution to infection and disease is often underappreciated, even among scientists, says Pyle, a Howard Hughes Medical Institute Investigator at Yale University.

Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland

The general wisdom is that if we just focus on the proteins encoded in the virus’s genome, we’ll understand how SARS-CoV-2 works,” Pyle says. “But for these types of viruses, RNA structures in the genome can influence their ability to function as much as encoded proteins.”

Researchers can now begin to tease out just how these structures aid the virus—information that could ultimately lead to new treatments for COVID-19. Once scientists have identified RNA structures that carry out key tasks, for instance, it may be possible to devise ways to disrupt them—and interfere with infection.

Source: https://www.hhmi.org/

Breakthrough Against COVID-19

A team of scientists from Stanford University is working with researchers at the Molecular Foundry, a nanoscience user facility located at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), to develop a gene-targeting, antiviral agent against COVID-19. Last year, Stanley Qi, an assistant professor in the departments of bioengineering, and chemical and systems biology at Stanford University and his team had begun working on a technique called PAC-MAN – or Prophylactic Antiviral CRISPR in human cells – that uses the gene-editing tool CRISPR to fight influenza.

But that all changed in January, when news of the COVID-19 pandemic emerged. Qi and his team were suddenly confronted with a mysterious new virus for which no one had a clear solution.

Lipitoids, which self-assemble with DNA and RNA, can serve as cellular delivery systems for antiviral therapies that could prevent COVID-19 and other coronavirus infections.

So we thought, ‘Why don’t we try using our PAC-MAN technology to fight it?’” said Qi.

Since late March, Qi and his team have been collaborating with a group led by Michael Connolly, a principal scientific engineering associate in the Biological Nanostructures Facility at Berkeley Lab’s Molecular Foundry, to develop a system that delivers PAC-MAN into the cells of a patient.

Like all CRISPR systems, PAC-MAN is composed of an enzyme – in this case, the virus-killing enzyme Cas13 – and a strand of guide RNA, which commands Cas13 to destroy specific nucleotide sequences in the coronavirus’s genome. By scrambling the virus’s genetic code, PAC-MAN could neutralize the coronavirus and stop it from replicating inside cells.

Qi said that the key challenge to translating PAC-MAN from a molecular tool into an anti-COVID-19 therapy is finding an effective way to deliver it into lung cells. When SARS-CoV-2, the coronavirus that causes COVID-19, invades the lungs, the air sacs in an infected person can become inflamed and fill with fluid, hijacking a patient’s ability to breathe.

But my lab doesn’t work on delivery methods,” he said. So on March 14, they published a preprint of their paper, and even tweeted, in the hopes of catching the eye of a potential collaborator with expertise in cellular delivery techniques. Soon after, they learned of Connolly’s work on synthetic molecules called lipitoids at the Molecular Foundry. Lipitoids are a type of synthetic peptide mimic known as a “peptoid” first discovered 20 years ago by Connolly’s mentor Ron Zuckermann. In the decades since, Connolly and Zuckermann have worked to develop peptoid delivery molecules such as lipitoids. And in collaboration with Molecular Foundry users, they have demonstrated lipitoids’ effectiveness in the delivery of DNA and RNA to a wide variety of cell lines.

Today, researchers studying lipitoids for potential therapeutic applications have shown that these materials are nontoxic to the body and can deliver nucleotides by encapsulating them in tiny nanoparticles just one billionth of a meter wide – the size of a virus. Now Qi hopes to add his CRISPR-based COVID-19 therapy to the Molecular Foundry’s growing body of lipitoid delivery systems.

Source: https://newscenter.lbl.gov/

New Biosensor Measures The Concentration Of Covid-19 In The Air

A team of researchers from Empa, ETH Zurich and Zurich University Hospital has succeeded in developing a novel sensor for detecting the new coronavirus. In future it could be used to measure the concentration of the virus in the environment – for example in places where there are many people or in hospital ventilation systems.

Jing Wang and his team at Empa and ETH Zurich usually work on measuring, analyzing and reducing airborne pollutants such as aerosols and artificially produced nanoparticles. However, the challenge the whole world is currently facing is also changing the goals and strategies in the research laboratories. The new focus: a sensor that can quickly and reliably detect SARS-CoV-2 – the new coronavirus.

But the idea is not quite so far removed from the group’s previous research work: even before the COVID-19 began to spread, first in China and then around the world, Wang and his colleagues were researching sensors that could detect bacteria and viruses in the air. The sensor will not necessarily replace the established laboratory tests, but could be used as an alternative method for clinical diagnosis, and more prominently to measure the virus concentration in the air in real time: For example, in busy places like train stations or hospitals.

Fast and reliable tests for the new coronavirus are urgently needed to bring the pandemic under control as soon as possible. Most laboratories use a molecular method called reverse transcription polymerase chain reaction, or RT-PCR for short, to detect viruses in respiratory infections. This is well established and can detect even tiny amount of viruses – but at the same time it can be time consuming and prone to error.

Jing Wang and his team have developed an alternative test method in the form of an optical biosensor. The sensor combines two different effects to detect the virus safely and reliably: an optical and a thermal one.

The sensor uses an optical and a thermal effect to detect the COVID-19-Virus safely and reliably

The sensor is based on tiny structures of gold, so-called gold nanoislands, on a glass substrate. Artificially produced DNA receptors that match specific RNA sequences of the SARS-CoV-2 are grafted onto the nanoislands. The coronavirus is a so-called RNA virus: Its genome does not consist of a DNA double strand as in living organisms, but of a single RNA strand. The receptors on the sensor are therefore the complementary sequences to the virus’ unique RNA sequences, which can reliably identify the virus.

The technology the researchers use for detection is called LSPR, short for localized surface plasmon resonance. This is an optical phenomenon that occurs in metallic nanostructures: When excited, they modulate the incident light in a specific wavelength range and create a plasmonic near-field around the nanostructure. When molecules bind to the surface, the local refractive index within the excited plasmonic near-field changes. An optical sensor located on the back of the sensor can be used to measure this change and thus determine whether the sample contains the RNA strands in question.

Source: https://www.empa.ch/

Why Are HIV Drugs Being Used to Treat the Coronavirus?

On Tuesday, the Japanese government announced it will begin clinical trials to test treatments for the deadly new coronavirus that’s engulfed China and spread to over two dozen countries. Rather than new drugs, they’ll be studying existing medications already used to treat HIV and other viral diseases. But why exactly are researchers hopeful that these drugs can be repurposed for the new coronavirus, and how likely are they to work?

The new coronavirus, recently named SARS-CoV-2 due to its close genetic ties to the SARS coronavirus, is made out of RNA. Other RNA viruses include the ones that cause Ebola, hepatitis C, and yes, HIV/AIDS.

RNA viruses come in all shapes and sizes, and those that infect humans can do so in different ways. But many of the drugs that go after HIV and the hepatitis C virus broadly target weaknesses found in all sorts of viruses. The approved hepatitis C drug ribavirin, for instance, interferes with something called the RNA-dependent RNA polymerase, an enzyme essential for many virusesincluding coronaviruses—to produce more of themselves inside a cell. HIV drugs like lopinavir inhibit other enzymes that allow viruses to break down certain proteins, which cripples their ability to infect cells and replicate.

Broad antiviral drugs like lopinavir should be able to work against SARS-CoV-2scientists theorize. And there’s already some circumstantial evidence they do. Some of these drugs have been successfully tested out for SARS and MERS, for instance, two other nasty coronaviruses that have emerged in recent years.

In January, the Chinese government announced a trial of 41 patients in Wuhan that would use a combination therapy of lopinavir and another HIV drug, ritonavir. In February, the Chinese government also began a trial using an experimental drug that’s been tested out for Ebola, called remdesivir.

Remdesivir has already been deployed during this outbreak, with seemingly impressive results so far. Last month, the first documented U.S. patient with the virus was treated with remdesivir, following a week of worsening symptoms that had developed into full-blown pneumonia. Within a day of receiving the drug through an IV, though, the man’s symptoms started to improve, and he was eventually released from the hospital.

But one case does not a surefire treatment make. And even if remdesivir or other drugs do prove effective against SARS-CoV-2, they’ll only play a small part in stopping this current outbreak from getting worse. Most cases of COVID-19 (the official name of the disease caused by SARS-COV-2) are still mild and won’t be helped much by antiviral drugs. In terms of preventing the next pandemic, it’s more important to keep people from getting the virus at all, rather than finding drugs to treat them once they do.

Source: https://gizmodo.com/

The Rising Of Gene Therapy

After false starts, drugs that manipulate the code of life are finally changing lives. The idea for gene therapy—a type of DNA-based medicine that inserts a healthy gene into cells to replace a mutated, disease-causing variant—was first published in 1972. After decades of disputed results, treatment failures and some deaths in experimental trials, the first gene therapy drug, for a type of skin cancer, was approved in China in 2003. The rest of the world was not easily convinced of the benefits, however, and it was not until 2017 that the U.S. approved one of these medicines. Since then, the pace of approvals has accelerated quickly. At least nine gene therapies have been approved for certain kinds of cancer, some viral infections and a few inherited disorders. A related drug type interferes with faulty genes by using stretches of DNA or RNA to hinder their workings. After nearly half a century, the concept of genetic medicine has become a reality.

These treatments use a harmless virus to carry a good gene into cells, where the virus inserts it into the existing genome, canceling the effects of harmful mutations in another gene.

GENDICINE: China’s regulatory agency approved the world’s first commercially available gene therapy in 2003 to treat head and neck squamous cell carcinoma, a form of skin cancer. Gendicine is a virus engineered to carry a gene that has instructions for making a tumor-fighting protein. The virus introduces the gene into tumor cells, causing them to increase the expression of tumor-suppressing genes and immune response factors.The drug is still awaiting FDA approval.

GLYBERA: The first gene therapy to be approved in the European Union treated lipoprotein lipase deficiency (LPLD), a rare inherited disorder that can cause severe pancreatitis. The drug inserted the gene for lipoprotein lipase into muscle cells. But because LPLD occurs in so few patients, the drug was unprofitable. By 2017 its manufacturer declined to renew its marketing authorization; Glybera is no longer on the market.

IMLYGIC: The drug was approved in China, the U.S. and the E.U. to treat melanoma in patients who have recurring skin lesions following initial surgery. Imlygic is a modified genetic therapy inserted directly into tumors with a viral vector, where the gene replicates and produces a protein that stimulates an immune response to kill cancer cells.

KYMRIAH: Developed for patients with B cell lymphoblastic leukemia, a type of cancer that affects white blood cells in children and young adults, Kymriah was approved by the FDA in 2017 and the E.U. in 2018. It works by introducing a new gene into a patient’s own T cells that enables them to find and kill cancer cells.

LUXTURNA: The drug was approved by the FDA in 2017 and in the E.U. in 2018 to treat patients with a rare form of inherited blindness called biallelic RPE65 mutation-associated retinal dystrophy. The disease affects between 1,000 and 2,000 patients in the U.S. who have a mutation in both copies of a particular gene, RPE65. Luxturna delivers a normal copy of RPE65 to patients’ retinal cells, allowing them to make a protein necessary for converting light to electrical signals and restoring their vision.

STRIMVELIS: About 15 patients are diagnosed in Europe every year with severe immunodeficiency from a rare inherited condition called adenosine deaminase deficiency (ADA-SCID). These patients’ bodies cannot make the ADA enzyme, which is vital for healthy white blood cells. Strimvelis, approved in the E.U. in 2016, works by introducing the gene responsible for producing ADA into stem cells taken from the patient’s own marrow. The cells are then reintroduced into the patient’s bloodstream, where they are transported to the bone marrow and begin producing normal white blood cells that can produce ADA.

YESCARTA: Developed to treat a cancer called large B cell lymphoma, Yescarta was approved by the FDA in 2017 and in the E.U. in 2018. It is in clinical trials in China. Large B cell lymphoma affects white blood cells called lymphocytes. The treatment, part of an approach known as CAR-T cell therapy, uses a virus to insert a gene that codes for proteins called chimeric antigen receptors (CARs) into a patient’s T cells. When these cells are reintroduced into the patient’s body, the CARs allow them to attach to and kill cancer cells in the bloodstream.

ZOLGENSMA: In May 2019 the FDA approved Zolgensma for children younger than two years with spinal muscular atrophy, a neuromuscular disorder that affects about one in 10,000 people worldwide. It is one of the leading genetic

causes of infant mortality. Zolgensma delivers a healthy copy of the human SMN gene to a patient’s motor neurons in a single treatment.

ZYNTEGLO: Granted approval in the E.U. in May 2019, Zynteglo treats a blood disorder called beta thalassemia that reduces a patient’s ability to produce hemoglobin, the protein in red blood cells that contains iron, leading to life-threatening anemia. The therapy has been approved for individuals 12 years and older who require regular blood transfusions. It employs a virus to introduce healthy copies of the gene for making hemoglobin into stem cells taken from the patient.The cells are then reintroduced into the bloodstream and transported to the bone marrow, where they begin producing healthy red blood cells that can manufacture hemoglobin.

The approach called ‘Gene Interference‘ uses a synthetic strand of RNA or DNA (called an oligonucleotide) that, when introduced into a patient’s cell, can attach to a specific gene or its messenger molecules, effectively inactivating them. Some treatments use an antisense method, named for one DNA strand, and others rely on small interfering RNA strands, which stop instruction molecules that go from the gene to the cell’s protein factories.

Source: https://www.nature.com/

Safe Stem Cells Therapies To Fight Alzheimer’s, Parkinson’s Diseases

A Rutgers-led team has created better biosensor technology that may help lead to safe stem cell therapies for treating Alzheimer’s and Parkinson’s diseases and other neurological disorders.

The technology, which features a unique graphene and gold-based platform and high-tech imaging, monitors the fate of stem cells by detecting genetic material (RNA) involved in turning such cells into brain cells (neurons), according to a study in the journal Nano Letters.

Stem cells can become many different types of cells. As a result, stem cell therapy shows promise for regenerative treatment of neurological disorders such as Alzheimer’s, Parkinson’s, stroke and spinal cord injury, with diseased cells needing replacement or repair. But characterizing stem cells and controlling their fate must be resolved before they could be used in treatments. The formation of tumors and uncontrolled transformation of stem cells remain key barriers.

This unique biosensing platform consists of an array of ultrathin graphene layers and gold nanostructures. The platform, combined with high-tech imaging (Raman spectroscopy), detects genetic material (RNA) and characterizes different kinds of stem cells with greater reliability, selectivity and sensitivity than today’s biosensors.

A critical challenge is ensuring high sensitivity and accuracy in detecting biomarkers – indicators such as modified genes or proteins – within the complex stem cell microenvironment,” said senior author KiBum Lee, a professor in the Department of Chemistry and Chemical Biology in the School of Arts and Sciences at Rutgers UniversityNew Brunswick.Our technology, which took four years to develop, has demonstrated great potential for analyzing a variety of interactions in stem cells.”

Source: https://news.rutgers.edu/

New Crispr Fixes 89% Of The Mutations That Cause Heritable Diseases

Andrew Anzalone was restless. It was late autumn of 2017. The year was winding down, and so was his MD/PhD program at Columbia. Trying to figure out what was next in his life, he’d taken to long walks in New York’s leaf-strewn West Village. One night as he paced up Hudson Street, his stomach filled with La Colombe coffee and his mind with Crispr gene editing papers, an idea began to bubble through the caffeine brume inside his brainCrispr, for all its DNA-snipping precision, has always been best at breaking things. But if you want to replace a faulty gene with a healthy one, things get more complicated. In addition to programming a piece of guide RNA to tell Crispr where to cut, you have to provide a copy of the new DNA and then hope the cell’s repair machinery installs it correctly. Which, spoiler alert, it often doesn’t. Anzalone wondered if instead there was a way to combine those two pieces, so that one molecule told Crispr both where to make its changes and what edits to make. Inspired, he cinched his coat tighter and hurried home to his apartment in Chelsea, sketching and Googling late into the night to see how it might be done. A few months later, his idea found a home in the lab of David Liu, the Broad Institute chemist who’d recently developed a host of more surgical Crispr systems, known as base editors. Anzalone joined Liu’s lab in 2018, and together they began to engineer the Crispr creation glimpsed in the young post-doc’s imagination. After much trial and error, they wound up with something even more powerful. The system, which Liu’s lab has dubbed “prime editing,” can for the first time make virtually any alterationadditions, deletions, swapping any single letter for any other—without severing the DNA double helix.

“If Crispr-Cas9 is like scissors and base editors are like pencils, then you can think of prime editors to be like word processors,” Liu told reporters in a press briefing. Why is that a big deal? Because with such fine-tuned command of the genetic code, prime editing could, according to Liu’s calculations, correct around 89 per cent of the mutations that cause heritable human diseases. Working in human cell cultures, his lab has already used prime editors to fix the genetic glitches that cause sickle cell anemia, cystic fibrosis, and Tay-Sachs disease. Those are just three of more than 175 edits the group unveiled in a scientific article published in the journal Nature.

The work “has a strong potential to change the way we edit cells and be transformative,” says Gaétan Burgio, a geneticist at the Australian National University who was not involved in the work, in an email. He was especially impressed at the range of changes prime editing makes possible, including adding up to 44 DNA letters and deleting up to 80. “Overall, the editing efficiency and the versatility shown in this paper are remarkable.”

Source: https://www.broadinstitute.org/

Biomimetic Nanoparticles Used As Carriers Improve AntiCancer Drugs

Researchers at the University of Helsinki in collaboration with researchers from Åbo Akademi University (Finland) and Huazhong University of Science and Technology (China) have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy. This new nano-tool provides a new approach to use cell-based nanomedicines for efficient cancer chemotherapy.

Exosomes contain various molecular constituents of their cell of origin, including proteins and RNA. Now the researchers have harnessed them together with synthetic nanomaterial as carriers of anticancer drugs. The new exosome-based nanomedicines enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma after intravenous administration.


The new exosome-based nanomedicines enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma after intravenous administration.

This study highlights the importance of cell-based nanomedicines”, says the principal investigator and one of the corresponding authors of this study, Hélder A. Santos, Associate Professor at the Faculty of Pharmacy, University of Helsinki.

Nanoparticles-based drug delivery systems have shown promising therapeutic efficacy in cancer. To increase their targetability to tumors, nanoparticles are usually functionalized with targeted antibodies, peptides or other biomolecules. However, such targeting ligands may sometimes have a negative influence on the nanoparticle delivery owing to the enhanced immune-responses.

Biomimetic nanoparticles on the other hand combine the unique functionalities of natural biomaterials, such as cells or cell membranes, and bioengineering versatility of synthetic nanoparticles, that can be used as an efficient drug delivery platform. The developed biocompatible exosome-sheathed porous silicon-based nanomedicines for targeted cancer chemotherapy resulted in augmented in vivo anticancer drug enrichment in tumor cells. “This demonstrates the potential of the exosome-biomimetic nanoparticles to act as drug carriers to improve the anticancer drug efficacy”, Santos concludes.

Source:  https://www.helsinki.fi/