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Modular Vaccine Platform

Following the pandemic, there is a clear need for improved technology in the area of vaccines. A pressing challenge is to enable a rapid response to emerging threats, using an established platform technology.

Small Molecules for Treating Clostridium perfringens-related Bacterial Infections

Researchers at the University of California, Davis have developed a method of treating infections caused by Clostridium perfringens bacteria - via inhibiting the bacteria’s normal quorum sensing processes.

Antibiotic to Fight Gram Negative and Resistant Bacteria

Researchers at the University of California, Davis have developed a gyramide antibiotic which is effective against Gram-negative and fluoroquinolones (FQs) resistant bacteria.

COVID-19 Risk Factor Biomarker and Prophylactic

Prof. Declan McCole and colleagues from the University of California, Riverside have identified a loss of function PTPN2 variant biomarker that may identify patients who are susceptible to SARS-CoV-2 infection. These patients have increased expression of ACE2, the receptor for SARS-CoV-2. Increased ACE2 has been tied with increased susceptibility to SARS-CoV-2. By identifying patients who are susceptible to SARS-CoV-2 infection, healthcare workers may reduce these patients’ risk of infection by prophylactically administering JAK inhibitors. Currently there is a debate in the medical community on whether or not patients should discontinue their JAK inhibitor therapies.  Clinicians believe that JAK inhibitors could decrease a patient’s immune response to fight COVID.  However these new findings suggest that ACE2 expression is decreased in individuals on a JAK inhibitor therapy. The findings detailed in this section suggests that patients can maintain their JAK inhibitor treatment since it can reduce expression of the receptor required by SARS-CoV-2 to cause infection. Fig 1: Lung epithelial cell line with PTPN2 knockdown (KD) facilitates entry of virus like particles (VLP) expressing the SARS-CoV-2 spike S protein. "(S)" is the SARS-CoV-2 spike protein with no additional protein. "(G)" is the positive control with the rhabdovirus vesicular stomatitis virus. ‘Ctr’ is the control lung epithelial cell.

Cyclic Peptide Inhibitors of The SARS-Cov-2 Main Protease

The SARS-CoV-2 virus has rapidly spread across the globe with severe medical, social, and economic costs. The Researchers at the University of California Irvine have designed novel cyclic peptide inhibitors based on a crystal structure of an inactive variant of SARS-CoV, known as Mpro318. Based on a small library of cyclic peptide inhibitors, some candidates showed promising in vitro activity at low micromolar concentrations.

Covidseeker. Digital Contact Tracing And Hotspotting In Real-Time

UCSF PIs developed a novel software platform for COVID-19 contact tracing and hotspotting called COVIDseeker. Covidseeker looks back in time and may be able to recreate people’s movements when infection rates were rising and falling in the spring and summer of 2020, giving epidemiologists an invaluable source of data as they try to predict what is going to happen in the fall and winter.This digital health invention has applications broader than COVID-19. The software can potentially be leveraged for other infectious diseases, treating obesity, and controlling smoking or alcohol addiction by showing where and when people are when they smoke, what are the triggers and how their location contributes to the risk of developing a particular disease.

Durable, Washable, and Reusable Antibacterial/Antiviral Cotton Fabrics

Researchers at the University of California, Davis have developed a durable and reusable cotton fabric that is antibacterial/antiviral, and has medical, first-responder, and other potential safety and public health applications.

Anti-microbial, Immune-modulating, Naturally-derived Adjunctive Therapies

Researchers at the University of California, Davis have developed adjunctive therapies applicable to multiple types of infectious conditions. These therapies – derived from compounds found in natural herbs - also have potential prophylactic efficacy.

A Broadly Neutralizing Molecule Against Clostridium Difficile Toxin B

Researchers at UCI have developed a family of recombinant protein therapeutics against Clostridium difficile designed to provide broad-spectrum protection and neutralization against all isoforms of its main toxin, TcdB. These antitoxin molecules feature fragments of TcdB’s human receptors which compete for TcdB binding, significantly improving upon existing antibody therapeutics for Clostridium difficile infections.

A Point Of Care Method To Detect Covid19 Infected And Immune Patients For Pennies

The emergence of a novel coronavirus disease (COVID-19) in late 2019 has caused a worldwide health and economic crisis. Determining which members of the population are infected is key to re-opening of schools, universities, and non-essential businesses. To address this, researchers at UCI and UIC have developed an inexpensive point of care test using RNA aptamer technology for detecting COVID19 infected and immune patients that can be taken at home like a pregnancy test.

COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTIONS

UC Berkley researchers have discovered compositions and methods for treating an RNA virus infection such as SARS-CoV-2 by administering an RNA-dependent RNA polymerase inhibitor, such as remdesivir, combined with a second FDA-approved therapeutic agent. Velpatasvir, Elbasvir, Dabrafenib, Omeprazole sulfide, Telmisartan, Selexipag, and Nifedipine are all FDA-approved molecules that have been shown to function synergistically with remdesivir for treating infection with an RNA virus.

Use of inhibitors and cell based therapies to combat a fatal immune response in COVID-19

UC researchers sought to define the host immune response, the “cytokine storm” , that has been implicated in fatal COVID-19 using an AI-based approach. Over 45,000 publicly available transcriptomic datasets of viral pandemics were analyzed to extract a 166-gene signature. The signature was surprisingly conserved in all viral pandemics, including COVID-19, inspiring the nomenclature ViP-signature. A subset of 20-genes classified disease severity in respiratory pandemics. The ViP signatures pinpointed airway epithelial and myeloid cells as the major contributors of an IL-15 cytokine storm, and epithelial and NK cell destruction as determinants of severity/fatality. They also helped formulate precise therapeutic goals to reduce disease symptoms and severity. Thus, the ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool in our armamentarium to rapidly assess disease severity and vet candidate drugs. 

METHODS OF TREATING SARS-COV-2 INFECTION USING INHIBITORS OF LIPOGENESIS

As of June 2020, the pandemic caused by SARS-CoV-2 infections (Coronaviral Disease 2019 (Covid-19)) caused about 9 million infections and about 460,000 deaths worldwide. The pandemic is expected to expand in the late 2020, particularly, because of the lack of a therapeutically effective treatment for the disease. Therefore, methods of treating SARS-CoV-2 infection are desired.   UC Berkeley inventors have developed methods of treating a SARS-CoV-2 infection in a patient infected with SARS-CoV-2 by administering to the patient a therapeutically effective amount of an inhibitor of lipogenesis. The inhibitor of lipogenesis can be an inhibitor of a lipogenic enzyme or an activator of 5’AMP-activated protein kinase (AMPK).  

Fluorescence Lifetime Imaging Microscopy Device for Antibiotic Susceptibility Testing (FLIM-AST)

Antibiotic resistant bacterial infection is a global public health threat leading to prolonged hospital stays, higher medical costs, and increased mortality rates. UCI researchers developed a device to rapidly determine antibiotic susceptibility of bacteria from patient samples to determine more effective antibiotic treatments.

Method to Enhance the Effectiveness of HIV Vaccines

Researchers at the University of California, Davis have developed adjuvants that promotes the efficacy of HIV vaccines.

Chronic Wound Mouse Model

Prof. Manuela Martins-Green and colleagues from the University of California, Riverside have developed a mouse model for chronic wounds in db/db-/- diabetic mice. Wounds are considered chronic when the body is unable to properly facilitate every stage of the healing process due to Oxidative Stress (OS), which occurs when an imbalance of redox chemicals exists in the damaged tissues. To create the chronic  wounds the mice were treated with inhibitors of antioxidant enzymes (IAE) at the time of wounding only. The wounds were then covered with tegaderm membranes and allowed to become chronic. Control wounds were treated with placebo. Fig 1: Percent open wound area over time in wounds of C57BL/6 and db/db-/- mice.  

COMPOSITIONS AND METHODS FOR IDENTIFYING HOST CELL TARGET PROTEINS FOR TREATING RNA VIRUS INFECTIONS

Viral infection is a multistep process involving complex interplay between viral life cycle and host immunity. One defense mechanism that hosts use to protect cells against the virus are nucleic-acid-mediated surveillance systems, such as RNA interference-driven gene silencing and CRISPR-Cas mediated gene editing. Another important stage for host cells to combat virus replication is translational regulation, which is particular important for the life cycle of RNA viruses, such as Hepatitis C virus and Coronavirus.  While efforts to characterize structural features of viral RNA have led to a better understanding of translational regulation, no systematical approaches to identify important host genes for controlling viral translation have been developed and little is known about how to regulate host-virus translational interaction to prevent and treat infections caused by RNA viruses.   UC Berkeley researchers have developed a high-throughput platform using CRISPR-based target interrogation to identify new therapeutics targets or repurposed drug targets for blocking viral RNA translation.  The new kits can also be used to identify important domains within target proteins that are required for regulating (viral RNA translation) and can inform drug design and development for treating RNA viruses.

Live Attenuated Vaccine Against Group A Streptococcus Infection

Streptococcus pyogenes (group A Streptococcus [GAS]) is a leading health and economic burden worldwide, with an estimated 700 million infections occurring annually. Among these are 18.1 million severe cases that result in over 500,000 deaths. Despite active research, a protective vaccine remains elusive, leaving antimicrobial agents as the sole pharmacological intervention against GAS. To date, penicillin remains a primary drug of choice for combating GAS infections. However, despite no apparent emergence of resistant isolates, the rate of treatment failures with penicillin has increased to nearly 40% in certain regions of the world. Due to the high prevalence of GAS infection and the decreasing efficacy of the available repertoire of countermeasures, it is critical to investigate alternative approaches against GAS infection. An emerging strategy for combating pathogenic bacteria involves targeting virulence. To avoid immune clearance, GAS expresses a wide variety of secreted and cell-associated virulence factors to facilitate survival during infection. Despite decades of inquiry into the role and regulation of GAS virulence factors, the function and potential importance of many proteins involved in pathogenicity remain unknown.

Novel Methods To Eliminate Dormant HIV Reservoirs

Human immunodeficiency virus type-1 (HIV-1) is a pathogenic retrovirus and the causative agent of acquired immunodeficiency syndrome (AIDS) and AIDS-related disorders. There were 1.7 million new infections globally in 2018, and ~38 million people are currently living with HIV-1. Although the introduction of antiretroviral therapy (ART) has prevented millions of AIDS-related deaths worldwide, patients must continue to receive ART for the remainder of their lives. HIV-1 reservoirs persist even while subjects are on ART, leading to a rapid increase in viral replication when therapy is discontinued. Therefore, eradication of persistent HIV-1 reservoirs remains the main barrier to achieving a cure for HIV-1/AIDS. The prevailing view of persistence suggests that the virus remains in a latent state in memory CD4+ T cells regardless of plasma viral loads, allowing the virus to establish a life-long infection in the host. Since the latent virus is refractory to existing antiretroviral therapies, curative strategies are now focusing on agents that reactivate viral replication and render it susceptible to conventional therapy. Any strategy aimed at controlling and eradicating viral reservoirs in HIV-1-infected individuals must target such latent reservoirs. The mammalian genome encodes thousands of long noncoding RNAs (lncRNAs, >200 nucleotides), including intergenic lncRNAs (lincRNAs), which are increasingly recognized to play major roles in gene regulation. The pathophysiological functions and mechanisms of lncRNAs in gene regulation have started to emerge. Work over the last few years has begun to uncover the role of lncRNAs in modulating HIV-1 gene expression.

Computational Cytometer Based On Magnetically-Modulated Coherent Imaging And Deep Learning

UCLA researchers in the Department of Electrical & Computer Engineering have designed and built a computational cytometer capable of detecting rare cells at low concentration in whole blood samples. This technique and instrumentation can be used for cancer metastasis detection, immune response characterization and many other biomedical applications.

Crosslinkable Polymer Coating Prevents Bacterial Infection on Implant Surface

UCLA researchers in the Department of Orthopedic Surgery have developed a polymer implant coating that mitigates bacterial infections on the implant surface.

TRM:CRAMP Knockout Mice In The C57bl/6 Background

The mouse Camp gene is an ortholog of the human gene CAMP, which encodes the precursor of cathelicidin antimicrobial peptide LL-37 (or CRAMP in mouse). Expressed mucosal epithelial cells, circulating neutrophils, and myeloid bone marrow cells, Camp is an essential part of the first line of defense against infection. In addition to antimicrobial activity, cathelicidin antimicrobial peptide plays a role in NK cell-mediated tumor growth suppression, and when secreted by neutrophils acts, as an attractant for monocytes, promoting wound healing or angiogenesis. Mouse CRAMP is implicated in adaptive immune response regulation and can interfere with TLR function via interactions with hyaluronan. Mice deficient in CRAMP are more susceptible to experimentally induced necrotic skin infection with Group A Streptococcus, urinary tract infection with uropathogenic E. coli, Pseudomonas aeruginosa infection, and meningococcal Neisseria meningitidis infection.

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