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

Researchers at the University of California, Davis, have developed a novel imaging system that improves the diagnostic accuracy of PET imaging. The system combines machine learning and computed tomography (CT) imaging to reduce noise and enhance resolution. This novel technique can integrate with commercial PET imaging systems, improving diagnostic accuracy and facilitating superior treatment of various diseases.

      Biologics are antibodies produced by genetically engineered cells and are widely used in therapeutic applications. Examples include pembrolizumab (Keytruda) and atezolizumab (Tecentriq), both employed in cancer immunotherapy as checkpoint inhibitors to restore T- cell immune responses against tumor cells. These biologics are produced by engineered cells in bioreactors in a process that is highly sensitive to the bioreactor environment, making it essential to integrate process analytical technologies (PAT) for closed-loop, real-time adjustments. Recent trends have focused on leveraging integrated circuit (IC) solutions for system miniaturization and enhanced functionality, for example enabling a single IC that monitors O2, pH, oxidation-reduction potential (ORP), temperature, and glucose levels. However, no current technology can directly and continuously quantify the concentration and quality of the produced biologics in real-time within the bioreactor. Such critical measurements still rely on off-line methods such as immunoassays and mass spectrometry, which are time-consuming and not suitable for real- time process control.       UC Berkeley researchers have developed a microsystem for real-time, in-vivo monitoring of antibody therapeutics using structure-switching aptamers by employing an integrator-based readout front-end. This approach effectively addresses the challenge of a 100× reduction in signal levels compared to the measurement of small-molecule drugs in prior works. The microsystem is also uniquely suited to the emerging paradigm of “living pharmacies.” In living pharmacies, drug-producing cells will be hosted on implantable devices, and real-time monitoring of drug production/diffusion rates based on an individual’s pharmokinetics will be crucial.

      Current clinical practice for detecting low-concentration molecular biomarkers requires sending samples to centralized labs, leading to high costs and delays. Successful point-of-care (POC) diagnostic technology exist, such as the paper-based lateral-flow assay (LFA) used for pregnancy tests and SARS-CoV-2 rapid antigen tests, or miniaturized instruments such as the Abbot i-Stat Alinity. However, the former provides binary results or limited quantitative accuracy, and the latter is too expensive for in-home deployment. A promising approach for POC diagnostics, offering tailored circuit optimization, multiplexed detection, and significant cost and size reductions, is millimeter-sized CMOS integrated circuits coupled with microfluidics. Recent demonstrations include protein, DNA/RNA, and cell detection. The current complexity of system packaging (e.g., wire/flip-chip bonding) makes integrating microfluidics with more sophisticated functions challenging, and often-required syringe pumps and tubing are operationally unfriendly, limiting current approaches.       UC Berkeley researchers have developed a fully integrated, multi-mode POC device that requires single-step assembly and operates autonomously. Drawing inspiration from RFID technology and implantables, they have introduced inductively-coupled wireless powering and communication functionality into a CMOS bio-analyzer. With the chip being fully wireless, the die can be easily integrated into a substrate carrier, achieving a completely flat surface that allows for seamless bonding with the microfluidic module. In the final product, the device will be sealed in a pouch inside a vacuum desiccator. The user tears the pouch, adds a drop of sample, and the system automatically begins operation. The operation window can last up to 40 minutes, making the process insensitive to time delays. The present CMOS bio-analyzer integrates pH-sensing and amperometric readout circuits for both proton-based and redox-based immunoassays.

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Inflatable pouches are attractive as actuators and structural links in soft robots due to their low deflated profile and high deformation ratio. Particularly compelling for minimally invasive surgery, deflated robots/actuators may be deployed in small form factors and maneuver delicately in tight spaces once inflated. However, current fabrication methods do not readily scale for production of actuators with less than 1 mm feature sizes; they often require precision handling of separator films; and/or there are limited multilayer integration capabilities. Fully miniaturized, high degree-of-freedom surgical pouch robots and actuators have not yet been realized.To overcome these challenges, UC Berkeley researchers have developed a rapid, monolithic, and scalable manufacturing method for fabricating thin-film-based pneumatic pouch soft robots. Small features (less than 0.3 mm) can be patterned at high speeds and using commercially available manufacturing tools while maintaining film planarity. Resulting robots can have complex, multilayer structures including single- and bi-directional joint actuators, structural links, integrated in-plane air channels, through-holes for interlayer connectivity, and air inlets to a supply manifold—from a single integrated processing step. Researchers have demonstrated a miniature four finger hand which can dexterously manipulate a cube (8 degrees of freedom), as well as an 10 degree-of-freedom planar arm with a gripper which can maneuver around obstacles. Entire pouch robot structures can have un-inflated thickness of less than 300 um and be inherently soft, allowing the robots to be used in tight spaces with fragile tissues for surgical applications.

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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.

Researchers at the University of California, Davis have developed multi-specific antibody molecules including bi-specific and tri-specific antibodies that could serve to co-localize effector T-cells, target tumor B-cells and would simultaneously enhance anti-tumor activity and proliferation, whilst minimizing potential systemic toxicities

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

Researchers at UC Irvine have identified and tested a molecular target that regulates T cell function during chronic viral infection and cancer. The molecular target is one of the high mobility group proteins (HMGB2). HMGB2 is a DNA binding protein that regulates transcriptional processes, meaning that its modulation will have profound effects on T cell differentiation and ultimate function by altering the expression of many genes.

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UC San Diego researchers synthesized a cell‐penetrating NEMOActPep where the NEMO peptide was fused to a peptide known to penetrate cell membrane. They also synthesized the corresponding mutant version where all six critical amino acids within this NEMOActPep were mutated to glycines.Currently, UC San Diego is looking for a company interested in developing US Patent Rights.

Plasma medicine has emerged as a promising approach for treatment of biofilm-related and virus infections, assistance in cancer treatment, and treatment of wounds and skin diseases. However, an important challenge arises with the need to adapt control policies, often only determined after each treatment and using limited observations of therapeutic effects. Control policy adaptation that accounts for the variable characteristics of plasma and of target surfaces across different subjects and treatment scenarios is needed. Personalized, point-of-care plasma medicine can only advance efficaciously with new control policy strategies.To address this opportunity, UC Berkeley researchers have developed a novel control scheme for tailored and personalized plasma treatment of surfaces. The approach draws from concepts in deep learning, Bayesian optimization and embedded control. The approach has been demonstrated in experiments on a cold atmospheric plasma jet, with prototypical applications in plasma medicine.

Immune responses are crucial in fighting against infections. An uncontrolled immune response, however, can be deadly. Sepsis is one such inflammatory disease that can lead to organ failure and death, so it is crucial to develop new sepsis therapies. Long noncoding RNAs (lncRNAs), although not translated into proteins themselves, can regulate gene expression in biological processes. Studies have shown that lncRNAs can regulate immune responses, which leads to substantial interest in implicating lncRNAs in inflammatory diseases.

Scientists have developed a CRISPR-Cas9 based genome editing method for universal correction of disease-causing mutations in the CTLA4 gene, which most commonly manifest as a Primary Immunodeficiency. Current treatment involves monthly IV injections or weekly subcutaneous injections of a recombinant CTLA4-Ig fusion protein abatacept. This invention includes one-time infusion of a CTLA4-corrected autologous T cell therapy. The corrected patient cells are generated by ex vivo electroporation of a specific gRNA:Cas9 ribonucleoprotien (RNP) complex and cognate homology-directed-repair template (HDRT) targeting a functional copy of the CTLA4 gene within an intronic region of the endogenous CTLA4 gene. This combination allows for (1) highly efficient knockin (up to 70% in patient cells), (2) cell-type and context specific regulation of CTLA4 expression under natural promoter and regulatory elements, and (3) preservation of endogenous CTLA4 expression in uncorrected cells.

Researchers at UCSF have developed methods of treating Rheumatoid arthritis and for predicting the response of patients to methotrexate. 

Researchers at UCSF and the Chan Zuckerberg Biohub have identified multiple common autoantibody targets in APS1 patients through proteome-wide programmable phage-display.

Professor Ameae Walker from the University of California, Riverside, Professor Srividya Swaminathan from the City of Hope Beckman Research Institute and their colleagues have developed a method for the prevention and treatment of B cell lymphomas. This technology works by systemically inhibiting expression of one form of the set of cell surface molecules that allow cells to respond to prolactin. This highly specific technology suppresses the deleterious downstream effects of prolactin that promote and sustain abnormal B cells. This invention is advantageous compared to existing technologies: all measures in mouse models and analysis of human cells suggest it is nontoxic and therefore will have significantly fewer, if any, side effects. It may also be used together with anti-psychotics that elevate prolactin. Finally, the technology includes a method for screening populations susceptible to development of DLBCL and other B lymphomas for early signs of disease. Antimaia Acts at Three Stages of B Lymphoma Development: 1) Antimaia, a splice modulating oligonucleotide (SMO) that decreases expression of the long form of the prolactin receptor, reduces the number of premalignant cells and the formation of abnormal antibody-producing cells. This also improves the symptomatology of autoimmune disease. 2) Antimaia prevents the conversion of premalignant to overt malignant B cells. 3) Antimaia kills B lymphoma cells. Antimaia works by reducing the number of long and intermediate form prolactin receptors (LF/IF PRLR) without effect on short receptors (SFPRLR). PRL, prolactin; Bcl2, B cell lymphoma 2; Myc, a proto-oncogene.

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Researchers at the University of California, Davis have developed a potential drug target for cancer and inflammation by studying the binding of integrins to P-selectin.

Researchers at the University of California, Davis have developed a potential therapeutic treatment for sepsis by modulating the interaction between integrins and Myeloid Differentiation factor 2 (MD-2).

Researchers from the University of California, Riverside have identified novel protease inhibitory mAbs including MMP-12, MMP-14, BACE-1, Alp2, and cathepsin mAbs. Matrix metalloproteinases MMP-12 and MMP-14 are involved in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. This technology is significant because these proteases precisely control a wide variety of physiological processes and thus are important drug targets for use in therapy for a wide range of diseases. Fig 1: Selection windows for the UCR cdMMP-14 inhibitors. β-lactamase TEM-1 was modified by insertion of the protease specific cleavage peptide sequences (shown in parentheses) between Gly196 and Glu197 of TEM-1.