Syndicate content

Archive - Apr 19, 2020

Date

Rockefeller University Launches Broad Range of Studies on COVID-19

Rockefeller University experts in infectious disease, immunology, biochemistry, structural biology, and genetics have begun over a dozen projects in recent weeks aimed at better understanding the biology of the SARS-CoV-2 virus, which is responsible for the current global COVID-19 pandemic. The research, which involves 18 laboratories and over 130 scientists, has the goal of discovering or developing new, urgently needed approaches to prevent and treat the disease. Although most Rockefeller laboratories have ceased on-campus operations to reduce the spread of the illness, exceptions have been made for those researchers working on essential COVID-19-related projects. Because the development, scale-up, and deployment of a safe and effective vaccine for the virus are still well over the horizon, the researchers are focusing on parallel approaches to provide alternative means of prevention and therapy, attacking the problem from many angles. Projects include the development of antibodies and other protein therapeutics capable of preventing or treating the infection; development of small molecules that inhibit the activity of viral or human proteins that are required for viral replication; improved animal models for testing potential treatments; and identification of new vulnerabilities of the virus via both genomic studies of humans with unusual sensitivity or resistance to infection, and cell-based screens using CRISPR gene-editing technology. “These projects directly relate to pathophysiology, prevention, and treatment of COVID-19, as well as the basic biology of the SARS-CoV-2 virus itself,” says Richard P. Lifton, MD, PhD, the university’s president.

MIT Scientists Design Water-Soluble, Modified Cytokine Receptors That Can Bind Cytokines; New Molecules May Prove Useful in Treating “Cytokine Storms” Associated with COVID-19 and Other Infections

One of the defining features of Covid-19 is the excessive immune response that can occur in severe cases. This burst of immune over-reaction, also called a cytokine storm, damages the lungs and can be fatal. A team of MIT researchers has developed specialized proteins, similar in structure to antibodies, that they believe could soak up these excess cytokines. “The idea is that they can be injected into the body and bind to the excessive cytokines as generated by the cytokine storm, removing the excessive cytokines and alleviating the symptoms from the infection,” says Rui Qing, PhD, an MIT research scientist who is one of the senior authors of the study. The researchers have reported their initial findings in Quarterly Review of Biophysics (QRB) Discovery, and they now hope to begin testing their proteins in human cells and in animal models of cytokine release and coronavirus infection. The article is titled “QTY Code-Designed Water-Soluble Fc-Fusion Cytokine Receptors Bind to Their Respective Ligands.” Shuguang Zhang, PhD, a principal research scientist in the MIT Media Lab’s Laboratory of Molecular Architecture, is also a senior author of the paper. Shilei Hao, PhD, a visiting scientist at MIT, is the lead author of the study, and David Jin, MD, PhD, CEO and President of Avalon GloboCare, is also an author. The researchers’ work on blocking cytokine storms grew out of a project that Dr. Zhang began ten years ago to develop modified versions of membrane-embedded proteins. These proteins are usually difficult to study because once they are extracted from the cell membrane, they only maintain their structure if they are suspended in special types of detergents. After working on the problem for several years, Dr. Zhang and Dr.

Princeton Researchers Design Shorter Promoters for Gene Delivery of Larger or Multiple Genes in Gene Therapy for Neurological Diseases; New Promoters Can Keep Transferred Genes Active for Long Periods of Time

A recently developed system for switching on the activity of genes could improve treatments for a broad range of neurological diseases. Esteban Engel, PhD, a researcher in viral neuroengineering in the Princeton Neuroscience Institute at Princeton University and Director of the Institute’s Viral Core Facility, and his team have developed new gene promoters, which act like switches to turn on gene expression, that promise to broaden the ability to deliver large genes and keep them active for long periods of time. The research was published online on April 14, 2020 in Molecular Therapy: Methods & Clinical Development. The open-access article is titled “Small Alphaherpesvirus Latency-Associated Promoters Drive Efficient and Long-Term Transgene Expression in the Central Nervous System.” [Please see video describing this work in press release at (https://www.eurekalert.org/pub_releases/2020-04/pu-nta041720.php)]. The team is developing these genetic switches for use in gene therapy, the practice of delivering new genes to replace or assist ones that are faulty. Gene therapy is a promising strategy for many diseases, including disorders that involve the brain, such as Parkinson's disease and Alzheimer's disease. To carry genes into cells, scientists take advantage of the fact that viruses come equipped with the machinery to gain entry to cells. Over the years, scientists have engineered viruses to deliver genes in ways that are safe and don't cause disease. One of the viruses commonly used for this is the relatively harmless adeno-associated virus (AAV). Dr. Engel and his team created new gene promoters that turn on genes after they have been transported into neurons, the cells of the brain and nervous system.