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In-situ Production of Anti-inflammatory Lipids for Treating Inflammation

Researchers at the University of California, Davis, have developed a process for isolating anti-inflammatory lipids for treating autoimmune and inflammatory diseases.

Systems and Methods of Single-Cell Segmentation and Spatial Multiomics Analyses

Researchers at the University of California, Davis have developed a novel cell segmentation technology for accurate analysis of non-spherical cells and that offers a comprehensive, high-throughput approach for analyzing the transcriptomic and metabolomic data to study complex biological processes at the single-cell level.

A Multi-Chip Module for Treatment of Ear/Brain Disorders

This unique device delivers electrical stimulation to the inner ear or cranial nerves to treat a panel of ear/brain disorders, including tinnitus.

(SD2022-222) Optimized CAG repeat‐targeting CRISPR/cas13d designs

Reseachers from UC San Diego demonstrated a proof of principle for a CAGEX RNA-targeting CRISPR–Cas13d system as a potential allele-sensitive therapeutic approach for HD, a strategy with broad implications for the treatment of other neurodegenerative disorders.

Compact Series Elastic Actuator Integration

      While robots have proven effective in enhancing the precision and time efficiency of MRI-guided interventions across various medical applications, safety remains a formidable challenge for robots operating within MRI environments. As the robots assume full control of medical procedures, the reliability of their operation becomes paramount. Precise control over robot forces is particularly crucial to ensure safe interaction within the MRI environment. Furthermore, the confined space in the MRI bore complicates the safe operation of human-robot interaction, presenting challenges to maneuverability. However, there exists a notable scarcity of force-controlled robot actuators specifically tailored for MRI applications.       To overcome these challenges, UC Berkeley researchers have developed a novel MRI-compatible rotary series elastic actuator module utilizing velocity-sourced ultrasonic motors for force-controlled robots operating within MRI scanners. Unlike previous MRI-compatible SEA designs, the module incorporates a transmission force sensing series elastic actuator structure, while remaining compact in size. The actuator is cylindrical in shape with a length shorter than its diameter and integrates seamlessly with a disk-shaped motor. A precision torque controller enhances the robustness of the invention’s torque control even in the presence of varying external impedance; the torque control performance has been experimentally validated in both 3 Tesla MRI and non-MRI environments, achieving a settling time of 0.1 seconds and a steady-state error within 2% of its maximum output torque. It exhibits consistent performance across low and high external impedance scenarios, compared to conventional controllers for velocity-sourced SEAs that struggle with steady-state performance under low external impedance conditions.

Cas13a RNP with Split gRNA for miRNA Detection

UC Berkeley researchers have developed systems and methods of using a split guide RNA (gRNA) to extend the lower size range of RNA detectable by Cas13a. When Cas13a is in complex with a split gRNA and capture RNA (capRNA), it can directly detect single-stranded RNA ranging from 8-24 nucleotides. The Cas13a split gRNA system is sensitive, enabling detection of femtomolar levels of RNA, and specific to sequence mismatches and gaps. We show that the split Cas13a RNP can detect miRNAs from extracted cell RNA. To detect a new RNA target, only the sequence of the capRNA needs to be modified; the same Cas13a RNP can be used for all targets. The capRNA can be tuned to maximize sensitivity of specificity, depending on the desired application. The split gRNA system expands the current use of Cas13a in molecular diagnostics and opens the door for its use in miRNA discovery.

Virus-encoded DNA-binding Proteins

Rapid virus evolution generates proteins essential to infectivity and replication but with unknown function due to extreme sequence divergence. Using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, it was found that 62% of viral proteins are structurally distinct and lack homologs in the Alphafold database. Structural comparisons suggested putative functions for >25% of unannotated viral proteins.  UC Berkeley researcher have created new single stranded DNA (ssDNA) bindingproteins and double stranded (dsDNA) binding proteins, and methods and compositions for using them, such as binding to target DNA.   

Multi-channel ZULF NMR Spectrometer Using Optically Pumped Magnetometers

         While nuclear magnetic resonance (NMR) is one of the most universal synthetic chemistry tools for its ability to measure highly specific kinetic and structural information nondestructively/noninvasively, it is costly and low-throughput primarily due to the small sample-size volumes and expensive equipment needed for stringent magnetic field homogeneity. Conversely, zero-to-ultralow field (ZULF) NMR is an emerging alternative offering similar chemical information but relaxing field homogeneity requirements during detection. ZULF NMR has been further propelled by recent advancements in key componentry, optically pumped magnetometers (OPMs), but suffers in scope due to its low sensitivity and its susceptibility to noise. It has not been possible to detect most organic molecules without resorting to hyperpolarization or 13C enrichment using ZULF NMR.         To overcome these challenges, UC Berkeley researchers have developed a multi-channel ZULF spectrometer that greatly improves on both the sensitivity and throughput abilities of state-of-the art ZULF NMR devices. The novel spectrometer was used in the first reported detection of organic molecules in natural isotopic abundance by ZULF NMR, with sensitivity comparable to current commercial benchtop NMR spectrometers. A proof-of-concept multichannel version of the ZULF spectrometer was capable of measuring three distinct chemical samples simultaneously. The combined sensitivity and throughput distinguish the present ZULF NMR spectrometer as a novel chemical analysis tool at unprecedented scales, potentially enabling emerging fields such as robotic chemistry, as well as meeting the demands of existing fields such as chemical manufacturing, agriculture, and pharmaceutical industries.

High-Speed, High-Memory NMR Spectrometer and Hyperpolarizer

         Recent advancements in nuclear magnetic resonance (NMR) spectroscopy have underscored the need for novel instrumentation, but current commercial instrumentation performs well primarily for pre-existing, mainstream applications. Modalities involving, in particular, integrated electron-nuclear spin control, dynamic nuclear polarization (DNP), and non-traditional NMR pulse sequences would benefit greatly from more flexible and capable hardware and software. Advances in these areas would allow many innovative NMR methodologies to reach the market in the coming years.          To address this opportunity, UC Berkeley researchers have developed a novel high-speed, high-memory NMR spectrometer and hyperpolarizer. The device is compact, rack-mountable and cost-effective compared to existing spectrometers. Furthermore, the spectrometer features robust, high-speed NMR transmit and receive functions, synthesizing and receiving signals at the Larmor frequency and up to 2.7GHz. The spectrometer features on-board, phase-sensitive detection and windowed acquisition that can be carried out over extended periods and across millions of pulses. These and additional features are tailored for integrated electron-nuclear spin control and DNP. The invented spectrometer/hyperpolarizer opens up new avenues for NMR pulse control and DNP, including closed-loop feedback control, electron decoupling, 3D spin tracking, and potential applications in quantum sensing.

Methods and Systems for Rapid Antimicrobial Susceptibility Tests

Rapid antimicrobial susceptibility testing (AST) is a method for quickly determining the most effective antibiotic therapy for patients with bacterial infections. These techniques enable the detection and quantification of antibiotic-resistant and susceptible bacteria metabolites at concentrations near or below ng/mL in complex media. Employing bacterial metabolites as a sensing platform, the system integrates machine learning data analysis processes to differentiate between antibiotic susceptibility and resistance in clinical infections within an hour. With the results, a clinician can prescribe appropriate medicine for the patient's bacterial infection.

High-Precision Chemical Quantum Sensing In Flowing Monodisperse Microdroplets

      Quantum sensing is rapidly reshaping our ability to discern chemical processes with high sensitivity and spatial resolution. Many quantum sensors are based on nitrogen-vacancy (NV) centers in diamond, with nanodiamonds (NDs) providing a promising approach to chemical quantum sensing compared to single crystals for benefits in cost, deployability, and facile integration with the analyte. However, high-precision chemical quantum sensing suffers from large statistical errors from particle heterogeneity, fluorescence fluctuations related to particle orientation, and other unresolved challenges.      To overcome these obstacles, UC Berkeley researchers have developed a novel microfluidic chemical quantum sensing device capable of high-precision, background-free quantum sensing at high-throughput. The microfluidic device solves problems with heterogeneity while simultaneously ensuring close interaction with the analyte. The device further yields exceptional measurement stability, which has been demonstrated over >103s measurement and across ~105 droplets.  Greatly surpassing the stability seen in conventional quantum sensing experiments, these properties are also resistant to experimental variations and temperature shifts. Finally, the required ND sensor volumes are minuscule, costing only about $0.63 for an hour of analysis. 

Allele Selective Epiediting Of Huntington's Disease Locus

Huntington's disease is an autosomal dominant neurodegenerative disease that has a wide impact on a person's functional abilities and usually results in movement, cognitive, and psychiatric disorders. A treatment for HD that can selectively reduce expression of a mutant copy of the HTT gene (e.g., while having little to no effect on expression of a normal copy of the HTT gene) is highly desirable.UC Berkeley researchers have discovered methods and compositions that take advantage of naturally occurring single nucleotide polymorphisms (SNPs) in the regulatory region of the HTT gene to distinguish between an HTT gene allele containing a pathogenic CAG trinucleotide repeat expansion and an HTT allele that lacks a pathogenic CAG trinucleotide repeat. Potential benefits of using this strategy include 1) lowering both mutant mRNA and mutant protein levels while normal allele remains unaffected, 2) lowering levels of toxic HTTexon11 species and 3) by lowering transcription across the mutant CAG repeats could slow down repeat expansion in mutant allele poten5ally leading to a delay in age of onset. 

O-Acetyl Glycosphingosines and Gangliosides, as well as Their N-Acetyl Analogs

Researchers at the University of California, Davis have developed a technology providing the creation of stable analogs of glycosphingosines and gangliosides containing O-acetylated sialic acid for extensive biological and medical applications.

Affinity Peptides for Diagnosis and Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 and Zika Virus Infections

Researchers at the University of California, Davis have developed a technology to expedite COVID-19 diagnosis and treatment using viral spike protein (S-protein) targeted peptides Zika virus envelop protein.

New Sulfoxide-Containing MS-Cleavable Cross-Linker for Proteomics

An innovative sulfoxide-containing MS-cleavable cross-linker, DBrASO, specifically designed for cysteine residues and aimed at enhancing protein-protein interactions studies and protein complexes architecture analysis.

New Cross-Linking Mass Spectrometry Platform: SDASO-L, SDASO-M, and SDASO-S

An innovative mass spectrometry platform that utilizes sulfoxide-containing MS-cleavable heterobifunctional photoactivated cross-linkers to enhance protein structural elucidation.

Compositions And Methods For Wound Healing

A breakthrough technology using insulin-secreting cells and stem cells to enhance wound healing and reduce scar formation.

Antisense Oligonucleotide Discovery Platform And Splice Modulating Drugs For Hemophilia

Aberrant splicing contributes to the etiology of many inherited diseases. Pathogenic variants impact pre-mRNA splicing through a variety of mechanisms. Most notably, variants remodel the cis-regulatory landscape of pre-mRNAs by ablation or creation of splice sites, and auxiliary splicing regulatory sequences such as exonic or intronic splicing enhancers (ESE and ISE, respectively) and splicing silencers (ESS and ISS, respectively). Splicing-sensitive variants cripple the integrity of the gene, resulting in the production of a faulty message that is either unstable or encodes an internally deleted protein. Antisense oligonucleotides (ASOs) are a promising therapeutic modality for rescuing pathogenic aberrant splicing patterns as their direct base pairing abilities make them highly customizable and specific to targets. Although challenges such as toxicity, delivery and stability represent barriers to the clinical translation of ASOs, solutions to these challenges exist, as exemplified by the recent FDA approval of multiple ASO drugs.Generally, ASO's that target splicing mutations are limited to mutations in and around splicing enhancers and exonic mutations are commonly not targeted because of the idea that the mutation causes a significant change in protein function. 

Engineering Pasteurella Multocida Heparosan Synthase 2 (Pmhs2) For Efficient Synthesis Of Heparosan Heparin And Heparan Sulfate Oligosaccharides

Researchers at the University of California, Davis have developed improved variants of a Heparosan synthase supporting efficient synthesis of heparosan, heparin, and heparan sulfate analogs.

Substrate And Process Engineering For Biocatalytic Synthesis And Facile Purification Of Human Milk Oligosaccharides (HMOs)

Researchers at the University of California, Davis have developed an innovative method for efficient, high-yield production and easy purification of Human Milk Oligosaccharides (HMOs) using a Multistep One-Pot Multienzyme (MSOPME) process.

Legionaminic Acid Glycosyltransferases for Chemoenzymatic Synthesis of Glycans and Glycoconjugates

Researchers at the University of California, Davis have developed a method for preparing a glycan product containing a nonulosonic acid moiety by means of legionaminic acid transferase fusion proteins

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