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Antiviral Compounds for HIV and Other Viral Infections

This invention identifies a novel class of HIV inhibitors targeting RNA-protein interactions.

Novel Small Protein Inhibitors for Rapid and Controllable CRISPR-Cas9 Interference

This invention identifies a novel class of natural protein-based inhibitors of CRISPR-Cas9, which could eliminate off-target effects of Cas9-mediated gene editing. It also presents an attractive antibiotic strategy and a potential biodefense agent against CRISPR bioterror threat.

A Novel Method to Generate Specific and Permanent Macromolecular Covalent Inhibitors

UCSF researchers have invented a novel method to generate covalent macromolecular inhibitors. This strategy allows a peptide inhibitor to bind to its target protein specifically and irreversibly through proximity-enabled bioreactivity.

Novel Method Of Imaging Infection Using Radiotracers

UCSF researchers have invented novel radiotracers that allow imaging of both gram-positive and gram-negative bacteria infections using positron emission tomography (PET) to detect spread of infection and to distinguish that from other mimics.

A Mouse Model of Human Papillomavirus (HPV) infection for Drug Discovery

UCSF researchers have generated and validated a K14-HPV16 transgenic mouse model, in which transgene expression produces neoplastic progression that fully resembles the gynecological and other epithelial dysplastic lesions induced by high risk HPVs. This model offers an invaluable tool for studying HPV infection and developing new drugs for HPV treatment.

A Novel Therapeutic Against HIV Using Human T Cell Immunoglobulin Mucin (TIM-3) Ligands to Modulate Immune Response

Blocking human T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) signaling can restore functionality to defective T cells in HIV-1 infected patients. Additionally, measuring TIM-3 provides clinicians with a novel way of evaluating, staging, and monitoring the progression of HIV infections.

A Gene Expression Panel For Diagnosis Of Ebola Virus Infection

This invention identifies a novel host gene expression panel to screen for the Ebola virus in pre-symptomatic patients.

Small Molecule Targeting HSP70 for Antiviral Therapy

Inhibitors of host Heat Shock Protein-70 (HSP70) as antiviral agents

Methods for Real-Time Sequencing Analysis of Infectious Diseases

A novel point-of-care technology enables real-time analysis and visualization of metagenomic sequence data for pathogen detection using a device that generates long sequencing reads at low cost and high speed with minimal sample preparation and instrumentation.

A Novel Tumor Targeting Strategy for Cancer Chemotherapy

A novel small molecule tumor-activated prodrug technology that produces a therapeutic index multiplying effect, leading to reduced drug-associated toxicity and improved efficacy in cancer patients.

Collaboration Opportunity: Novel Mouse Models of Human Hepatitis B Virus Infection for Drug Discovery and Vaccine Research

HBV infection can lead to chronic infections that result in 0.6 million deaths per year worldwide by causing liver failure and cancer. Clearance of HBV infection is age dependent, with the majority of adult-acquired infections leading to spontaneous clearance, whereas infection in young children often leads to chronic infections. To study these early events of infection and immune activation that lead to HBV clearance or persistence, in vivo models are needed to screen and validate lead drug candidates. HBV cannot infect mice, however, researchers at UCSF have generated transgenic mouse models that mimic critical features of primary HBV infection observed in humans.

Chemically Novel Beta-Lactamase Inhibitors

The market for new therapeutic products that will combat resistant strains of infectious pathogens commands $26 billion annually.  The U.S. market share for new generation antibiotics alone is expected to reach $10 billion this year.  To overcome the growing problem of microbial resistance, drug development companies have adopted a number of strategies based on the production of beta-lactamases, including developing new beta-lactamase inhibitors that can be co-administered with beta-lactam antibiotics.  This particular strategy has yielded three beta-lactamase inhibitors are all active against most class A enzymes, such as TEM-1, but not against class C enzymes, like AmpC.  Also, these inhibitors afford no protection to cephalsoporins clinically and have never been combined, for example, with the 3rd generation cephalosporins, leaving these widely used drugs susceptible to the evolution of the extended spectrun beta-lactamases (ESBLs).  Thus there is pressing need for new inhibitors that can be combined with a primary beta-lactam, especially a cephalosporin, rescuing these first-line antibiotics for continued clinical utility.

Apicoplast-Deficient, Attenuated Strains of Plasmodium for Use as Malaria Vaccines

Currently, no malaria vaccines are available for clinical use. The need for a vaccine is also compounded by the emergence of multiple drug-resistant Plasmodium strains. In 2008, there were nearly 250 million cases of malaria and one million deaths worldwide according to the World Health Organization. Moreover, in addition to chloroquine resistance, resistance to newer anti-malarials is growing. Thus, innovative vaccines and anti-malarials are needed to reduce the morbidity and mortality caused by malaria infections in humans.

Endogenous Small Molecule Immune Response Modulator

UCSF investigators have identified a novel endogenous agent that activates the Aryl Hydrocarbon Receptor.

NOVEL PRENATAL DIAGNOSTIC BIOMARKERS FOR CYTOMEGALOVIRUS INFECTION

UCSF researchers have identified novel biomarkers of CMV replication that permit early detection of virus transmission before the onset of symptomatic disease. Quantification of these biomarkers is a more sensitive and reliable method than detection of viral DNA and therefore could result in novel tests for diagnosis of congenital infection in early gestation. Additionally, these biomarkers could be used to measure efficacy of treatment in pregnancies at high risk for congenital CMV disease and to serve as endpoints for successful antiviral therapy.

STRAINS AND PLASMIDS FOR MAKING HOMOZYGOUS KNOCKOUTS IN C. ALBICANS

Researchers at UCSF have developed new C. albicans strains that use different auxotrophic markers that do not affect the virulence of C. albicans in a mouse model. Furthermore, these researchers have cloned complementing markers to be used in selection of knockout mutants from Candida strains other than C. albicans, thereby greatly reducing misintegration of DNA gene disruption fragments into the Candida auxotrophic marker site instead of the knockout target site. Combining these strains and markers with a fusion PCR technique allows for quick and efficient disruption of both alleles of the target gene in C. albicans. Generating homozygous knockouts is improved from 2% to 70% efficiency for knocking out the more difficult second allele.

POTENT DOMINANT NEGATIVE TRANSCRIPTIONAL INHIBITORS

BACKGROUND:  The regulation of gene expression by transcription factors is a fundamental aspect of the physiology of all cells. The aberrant expression of transcription factors can lead to abnormal development and various diseases, like cancer and heart defects. One disease which might be approached by modulating transcription factor function is acquired immune deficiency syndrome (AIDS), caused by the retrovirus HIV, which incorporates itself into the host cell via reverse transcription of its RNA. Several therapeutics exist currently that target various critical points in the HIV life cycle, however, used alone, these drugs have low effectiveness and cannot prevent the virus from developing resistance to these known agents. Effective new methods of targeting underexploited aspects of the HIV life cycle, such as transcription of the HIV virus, remain desirable.   TECHNOLOGY:  The present invention was conceived as a dominant negative regulator of the Tat transcription factor, thus leading to the inhibition of HIV-1 transcription. More broadly, this application can be used to generate multiple potent dominant negative regulators of transcription by linking a transcription factor to a protein that localizes to the transcriptional machinery.

Novel Pro-Drug Technology for Targeted Delivery of Therapeutic Agents

UCSF investigators have developed a novel targeted pro-drug technology that can selectively deliver a chemotherapeutic payload to cells in areas of high concentrations of endogenous free ferrous iron. The pro-drug can be conjugated to a variety of existing and novel pharmacologically active compounds to increase their therapeutic window and lower systemic toxicity by increasing the selectivity of their delivery. Applications include therapies for cancer and malaria and as imaging agents. 

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