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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.

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.

Stable N-acetylated analogs of Sialic Acids and Sialosides

Researchers at the University of California, Davis have constructed a library of glycans containing N-acetyl sialic acids to mimic those containing naturally occurring O-acetyl sialic acids.

2-D Polymer-Based Device for Serial X-Ray Crystallography

Researchers at the University of California, Davis have developed a single-use chip for the identification of protein crystals using X-ray based instruments.

One-Pot Multienzyme Synthesis of Sialidase Reagents, Probes and Inhibitors

Researchers at the University of California, Davis, have developed an environmentally friendly one-pot multienzyme (OPME) method for synthesizing sialidase reagents, probes, and inhibitors.

DNA-based, Read-Only Memory (ROM) for Data Storage Applications

Researchers at the University of California, Davis have collaborated with colleagues at the University of Washington and Emory University to develop a DNA-based, memory and data storage technology that integrates seamlessly with semiconductor-based technologies and conventional electronic devices.

Synthesis of Capsular Polysaccharides

Researchers at the University of California, Davis have developed a more cost effective and consistent method for producing capsular polysaccharides, a component of certain types of vaccines.

Novel PET Plastic Degrading Enzyme

Prof. Adam Godzik and colleagues from the University of California, Riverside have developed an enzyme with the potential of high PET degrading ability. Based on computer modeling experiments, this enzyme has the potential of high PET degrading ability. This enzyme may be useful because it may have higher PET degrading activity than existing enzymes and could provide a less expensive and more efficient means of recycling PET plastic. Fig 1: Predicted structure of the UCR PET degrading enzyme.

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.

Highly Effective Broad Spectrum Mosquito Larvacide

Prof. Brian Federici and his colleagues from the University of California, Riverside have developed a highly effective commercial larvicide based on two mosquitocidal bacteria, Bacillus thuringiensis subsp. israelensis (Bti) and Lysinibacillus sphaericus (Ls). By using specific chimeric proteins, this method allows for a broad-spectrum targeting domain for insecticidal proteins. Results have shown that this larvicide will have high efficacy against most major mosquitoes that transmit diseases, including Malaria, Yellow Fever, Filariasis, and newly emerging viruses such as the Zika virus. This technology serves to confront the growing need for preventing deadly diseases from being spread by insects in order to save lives. Fig 1: Midgut histopathology caused by Cyt1Aa-BinA chimera in 8 hours post-treatment at the LC95 concentration; Control midgut epithelium, (i) and (ii), respectively, 100x and 400x magnification. Midgut epithelium of a treated larva (iii) and (iv), respectively 100x and 600x magnification.  

Deep Learning Techniques For In Vivo Elasticity Imaging

Imaging the material property distribution of solids has a broad range of applications in materials science, biomechanical engineering, and clinical diagnosis. For example, as various diseases progress, the elasticity of human cells, tissues, and organs can change significantly. If these changes in elasticity can be measured accurately over time, early detection and diagnosis of different disease states can be achieved. Elasticity imaging is an emerging method to qualitatively image the elasticity distribution of an inhomogeneous body. A long-standing goal of this imaging is to provide alternative methods of clinical palpation (e.g. manual breast examination) for reliable tumor diagnosis. The displacement distribution of a body under externally applied forces (or displacements) can be acquired by a variety of imaging techniques such as ultrasound, magnetic resonance, and digital image correlation. A strain distribution, determined by the gradient of a displacement distribution, can be computed (or approximated) from measured displacements. If the strain and stress distributions of a body are both known, the elasticity distribution can be computed using the constitutive elasticity equations. However, there is currently no technique that can measure the stress distribution of a body in vivo. Therefore, in elastography, the stress distribution of a body is commonly assumed to be uniform and a measured strain distribution can be interpreted as a relative elasticity distribution. This approach has the advantage of being easy to implement. The uniform stress assumption in this approach, however, is inaccurate for an inhomogeneous body. The stress field of a body can be distorted significantly near a hole, inclusion, or wherever the elasticity varies. Though strain-based elastography has been deployed on many commercial ultrasound diagnostic-imaging devices, the elasticity distribution predicted based on this method is prone to inaccuracies.To address these inaccuracies, researchers at UC Berkeley have developed a de novo imaging method to learn the elasticity of solids from measured strains. Our approach involves using deep neural networks supervised by the theory of elasticity and does not require labeled data for the training process. Results show that the Berkeley method can learn the hidden elasticity of solids accurately and is robust when it comes to noisy and missing measurements.

Gasdermin-D Deficient Mice

UC researchers created a Gasdermin-D deficient mice that carry a CRISPR/Cas9-derived knock-out allele of the mouse Gsdmd gene that involves a 19 bp and a 1 bp (20 bp total) insertion in exon 2. 

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.

Injectable Extracellular Matrix For Treating Skeletal Muscle Atrophy And Degeneration

The primary therapeutic goal in female pelvic medicine is to restore normal pelvic floor function. Despite this, the current standard treatments are 5 compensatory, as they do not directly target sphincteric and supportive muscle dysfunction and do not reverse the existing injury or halt functional deterioration. Surgical treatments, such as muscle transplantation and transposition techniques, have had some success; however, there still exists a need for alternative therapies. Tissue engineering approaches offer potential new solutions; however, current options offer incomplete regeneration. Many naturally derived as well as synthetic materials have been explored as scaffolds for skeletal tissue engineering, but none offer a complex mimic of the native skeletal extracellular matrix, which possesses important cues for cell survival, differentiation, and migration. The extracellular matrix consists of a complex tissue-specific network of proteins and polysaccharides, which help regulate cell growth, survival and differentiation.Despite the complex nature of native ECM, in vitro cell studies traditionally assess cell behavior on single ECM component coatings, thus posing limitations on translating findings from in vitro cell studies to the in vivo setting. Overcoming this limitation is important for cell-mediated therapies, which rely on cultured and expanded cells retaining native cell behavior over time.Skeletal muscles are composed of bundles of highly oriented and dense muscle fibers, each a multinucleated cell derived from myoblasts. The muscle fibers in native skeletal muscle are closely packed together in an extracellular three dimensional matrix to form an organized tissue with high cell density and cellular orientation to generate longitudinal contraction. Skeletal muscle can become dysfunctional due to a variety of different factors including trauma, atrophy or degeneration.The reconstruction of skeletal muscle, which is lost by injury, tumor resection, or various myopathies, is limited by the lack of functional substitutes.  

Implantable Substance Delivery Devices

This invention describes a method for preparing an implantable device made from biocompatible polymers for sustained delivery of a substance within a body of human or an animal.

XNA enzymes to Validate and Treat Genetic Diseases

Allelic proteins are often considered undruggable targets, because therapeutics that interfere with these proteins while leaving the wild-type protein unharmed are difficult to come by. Researchers at UCI have developed a xeno-nucleic enzyme (XNAzyme) that offers a solution to this problem by selectively cleaving the mRNA of mutant alleles while leaving the wild-type mRNA unharmed. This novel gene silencing technology offers an efficient, safe, and effective approach to treating genetic diseases.

Oxime Crosslinked Hydrogels To Prevent Postsurgical Cardiac Adhesions

Although a wide variety of hydrogels have been developed for a multitude of uses, various functional characteristics have been hard to capture in a controllable manner. A significant feature is the ability to ‘tune’ the gel so its gelling time can be controlled in a manner suitable to its application. In this disclosure, because the gel is both tunable and its composition allows it to bond to tissue, the inventors believe it can be used to address an unmet medical need – the formation of adhesions after cardiac surgery. Current methods used are either drug therapy or various physical barriers but their success is limited.

Compositions And Methods For Allelic Gene Drive Systems And Lethal Mosaicism

Efficient super-Mendelian inheritance of transgenic insertional elements has been demonstrated in flies, mosquitoes, yeast, and mice. While numerous potentially impactful applications of such so-called gene-drive systems have been proposed they are currently limited to copying relatively large DNA cargo sequences (~1-10 Kb). Many desired genetic traits (e.g., drought tolerance in plants, crop yield, pest-resistance, or insecticide sensitivity), however, result from allelic variants altering only one or a few base pairs. An efficient system for super-Mendelian inheritance of such subtle genetic variants would accelerate a wide array of efforts to disseminate favorable traits throughout populations, or to assemble complex genotypes consisting of point-mutant alleles in combination with insertional transgenes for a multitude of research and applied purposes.

(SD2020-014) Biosynthetic Production Of L-4-Chlorokynurenine

The non‐proteinogenic amino acid l‐4‐chlorokynurenine (l‐4‐Cl‐Kyn) is a next‐generation, fast‐acting oral prodrug for the treatment of major depressive disorder. Additional studies report that this drug candidate is effective in animal models for the treatment of neuropathic pain, epilepsy, and Huntington's disease.  After active transport across the blood–brain barrier, it is enzymatically converted into the active agent 7‐chlorokynurenic acid, which is a highly selective competitive antagonist of the N‐methyl‐d‐aspartic acid (NMDA) receptor.   Suicide is 2-7x higher in Veterans than non-veterans, and may be related to brain kynurenine pathway (KP) dysregulation and NMDA receptor (NMDAR) hyperactivation.  L-4-Chlorokynurenine (L-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder (Double-Blind, Placebo-Controlled, Phase 2 Trial to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) as Adjunct to Current Antidepressant Therapy in Patients With Major Depressive Disorder (the ELEVATE Study)).

Antimicrobial and Osteoinductive Hydrogel for Dental Applications

UCLA researchers in the Department of Chemical & Biomolecular Engineering developed osteoinductive and antimicrobial hydrogel adhesives for dental applications.

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These technologies are part of the UC QuickStart program.