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Deep Learning-Based Approach to Accelerate T cell Receptor Design

Researchers at the University of California, Davis have developed a deep learning simulation model to predict mutated T-cell receptor affinity and avidity for immunotherapy applications.

High Accuracy Machine Learning Model for Predicting Liver Cancer Risk

Researchers at the University of California, Davis have developed a method to predict if patients diagnosed with nonalcoholic fatty liver disease are at risk for developing liver cancer using a machine learning algorithm that analyzes a variety of easily available phenotypes and risk factors.

Positive Allosteric Modulators Target TRPV1 with Analgesic Effects

Researchers at the University of California, Davis have developed de novo positive allosteric modulators (PAMs) that bind to TRPV1 proteins involved with pain-sensing in order to provide analgesic effects.

Novel Agonist alpha2aAR Analgesics

Brief description not available

Conjugates That Combine HDAC Inhibitors and Retinoids into Disease Preventatives/Treatments

Researchers at the University of California, Davis have developed methods for creating compositions with the potential to prevent or treat cancer or metabolic diseases. These compositions combine conjugates with covalently linked HDAC inhibitors and retinoids.

Acid Degradable Solid Lipid Nanoparticles

The inventors demonstrate that polyethylene glycol (PEG) conjugated to cholesterol via an acid degradable linkage composed of an azide-benzaldehyde acetal has the potential to allow solid lipid nanoparticles (SLNs) to be PEGylated with mole ratios up to 50%. The azide-benzaldehyde acetal, has its azide in the para position, and generates stable acetals with a t ½ of > 1000 minutes at pH 7.4. These PEG-acetals can be formulated into SLNs, and stored, and then reduced prior to biological use, to generate an amino acetal that has t ½ < 60 minutes at pH 7.4 and several minutes at pH 5.0. The ultra-PEGylated lipids were efficient at transfecting a variety of organs, including the muscle, the lung, spleen and liver and were also able to transfect the blood. Acid degradable PEG-lipids have great potential for overcoming the PEG dilemma, but have previously been challenging to develop due to the synthetic challenges associated with working with acetals and their instability at pH 7.4. (SLNs contain a PEGylated lipid, generally in the 1-5% range, which is needed to maintain SLN stability, size, and tissue diffusion, and lower toxicity. However, excessive PEGylation also results in lower cell uptake and endosomal disruption — a paradox referred to as the PEG dilemma.) The inventors anticipate numerous applications of the azide-benzaldehyde acetal linker, given its unique ability to be stable prior to reductive activation. 

Sialic Acid Inhibitor in Cancer Treatment and Immunotherapy

Researchers at the University of California, Davis have developed a method of inhibiting sialic acid expression which is commonly related to bacterial and viral infections, metastatic cancer, and other pathogenic processes.

Multiplex Epigenetic Editing using a Split-dCas9 System

Researchers at the University of California, Davis have developed a new epigenetic editing system that overcomes packaging limitations of viral delivery systems and can be used for multiplexed epigenetic editing of a genome.

Staged Fascial Closure Device

The current invention enables the safe closure of an open abdomen during surgery when the abdominal fascia cannot be closed primarily.

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.

Optimized Virus-like Particles for Cas9 RNPs & Transgene/HDR Template Delivery

The inventors have developed optimized methods for using virus-like particles for the co-delivery of Cas9 ribonucleoprotein complexes and: a lentiviral genome that encodes a large transgene, such as a chimeric angtigen receptor (CAR) transgene a lentiviral genome that does not encode a sgRNA expression cassette a method for nucleofecting VLPs + homology directed repair (HDR) donor template together to enhance HDR in treated cells  

Using Escherichia coli to Produce Human Milk Oligosaccharide Lactodifucotetraose

Researchers at the University of California, Davis have developed a method for producing human milk oligosaccharide lactodifuctotetraose (LDFT) using E. coli.

A Gene Therapy for treating Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a predominantly genetic-based heart disease characterized by right but also recently left ventricular dysfunction, fibrofatty replacement of the myocardium leading to fatal/severe ventricular arrhythmias leading to sudden cardiac death in young people and athletes. ARVC is responsible for 10% of sudden cardiac deaths in people ≥65 years of age and 24% in people ≤30 years of age. ARVC is thought to be a rare disease as it occurs in 1 in 1000-5000 people, although the prevalence may be higher as some patients are undiagnosed or misdiagnosed due to poor diagnostic markers. Growing evidence also reveals earlier onset since pediatric populations ranging from infants to children in their teens are also particularly vulnerable to ARVC, highlighting the critical need to identify and treat patients at an earlier stage of the disease. At present there are no effective treatments for ARVC nor has there been any randomized clinical trials conducted to examine treatment modalities, screening regimens, or medications specific for ARVC. As a result, treatment strategies for ARVC patients are directed at symptomatic relief of electrophysiological defects, based on clinical expertise, results of retrospective registry-based studies, and the results of studies on model systems. The current standard of care is the use of anti-arrhythmic drugs (sotalol, amniodarone and beta-blockers) that transition into more invasive actions, which include implantable cardioverter defibrillators and cardiac catheter ablation, if the patient becomes unresponsive or intolerant to anti-arrhythmic therapies. However, current therapeutic modalities have limited effectiveness in managing the disease, 40% of ARVC patients (a young heart disease) die within 10-11 years after initial diagnosis, highlighting the need for development of more effective therapies for patients with ARVC.

(SD2019-040) Directed modification of cellular RNA via nuclear delivery of CRISPR/Cas

Present strategies aimed to target and manipulate RNA in living cells mainly rely on the use of antisense oligonucleotides (ASO) or engineered RNA binding proteins (RBP). Although ASO therapies have been shown great promise in eliminating pathogenic transcripts or modulating RBP binding, they are synthetic in construction and thus cannot be encoded within DNA. This complicates potential gene therapy strategies, which would rely on regular administration of ASOs throughout the lifetime of the patient. Furthermore, they are incapable of modulating the genetic sequence of RNA. Although engineered RBPs such as PUF proteins can be designed to recognize target transcripts and fused to RNA modifying effectors to allow for specific recognition and manipulation, these constructs require extensive protein engineering for each target and may prove to be laborious and costly. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

High-yielding Extraction of Single-Stranded Nucleic Acids with Carbon Nanotubes

PCR amplification is widely used in basic biological research and medical diagnostic tests for various infectious diseases, and is a powerful tool for nucleic acid detection. Nucleic acid extraction is an important part of the overall workflow in PCR-based viral infection test, since its function is to separate out viral nucleic acid from the many other biological components in a nasal swab-derived sample. UC Berkeley researchers have developed a method for single-stranded nucleic acid extraction from complex biofluids with DNA-wrapped carbon nanotubes. Large viral single-stranded nucleic acids can be captured by corresponding DNA-wrapped carbon nanotubes and can be concentrated for subsequent polymerase chain reaction (PCR) amplification. This method can extract nucleic acids without complicated manufacturing and experimental processes, can generate higher extraction yields than a conventional commercial PCR kit, and fits into the current PCR workflow while requiring minimal chemical reagents.  

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.

Rapid Generation Of A Droplet Compound Library

The present invention features a device for rapidly formatting a chemical compound library into microfluidic droplets, addressing the challenge of interfacing between the macroscale and the microscale regimes of the production of reagent libraries of chemical compounds.

Delivery System For Transcatheter Valves

Researchers at UCI have developed a novel medical device for use in transcatheter heart valve replacement surgeries. The device provides physicians with more careful control of the catheter insertion, minimizing complications and adverse effects.

MicroRNA regulation of airway mucins for treatment of lung diseases

This invention describes a novel therapeutic microRNA target regulating mucus production for the management of symptoms caused by a range of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and the common cold. Recently, a specific miRNA, along with its highly homologous family members, has been shown to be dysregulated in asthmatic subjects. To modulate the effect of these miRNAs, antagomirs (which target specific endogenous miRNAs and dampen their effect) or miRNA mimics can be administered via an inhaler, allowing for the regulation of mucus production. This invention is at the preclinical stage, and in vivo testing in a mouse model of asthma has shown that treatment with a specific miRNA antagomir results in a significant reduction of airway mucus production. While there are currently no effective therapies targeting mucus production in the airways, miRNAs are a promising new avenue for therapeutic intervention as they are fast-acting and reversible. 

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