Innovative cell lines enabling precise genetic modifications to advance research in gene function, disease modeling, and potential therapeutic interventions.

Professor Kevin Kou and his team at the University of California, Riverside, in collaboration with Professor Wendong Huang's lab at City of Hope, have developed a new method for synthesizing modified versions of bersavine. Using this method, several novel bersavine compounds were synthesized. When these new compounds were tested against lymphoma cells, powerful anti-cancer effects were demonstrated. Notably, these newly synthesized analogs are more effective at inhibiting cell growth than the naturally occurring bersavine. 

A revolutionary drug modality for the selective modification and degradation of intracellular proteins in lysosomes.

This technology leverages X-ray-induced acoustic phenomena for real-time, in-line verification of photon beam location and dose during cancer radiotherapy.

Professor Kevin Kou and colleagues from the University of California, Riverside and the City of Hope National Medical Center have developed a chemical synthetic strategy that allows for the efficient generation of a diverse library of oxyberberine derivatives. This technology is advantageous because the family of protoberberine molecules, the best known being berberine, is generally considered non-toxic. As such, protoberberine derivatives are likely to elicit a better safety profile compared to existing AMPK inhibitors that are highly toxic and be developed to treat a range of diseases.  Fig 1: Four of the UCR novel AMPK inhibitors resulting from the UCR synthesis strategy.

A novel technology for real-time, non-invasive monitoring and adaptive control of electron radiotherapy treatments using acoustic signals.

A cutting-edge vaccine delivery platform that enhances tumor treatment by co-delivering MHC class I and II restricted antigens.

The targeted intracellular delivery of protein cargos is critical for therapeutic applications such as enzyme inhibition, transcriptional modulation, and genome editing. For most tissues, the delivery of these molecules must occur in-vivo. This has historically been achieved using viral vectors or lipid nanoparticles. While significant progress has been made in engineering the tropisms of these particles towards different tissues, delivery specificity and packaging limits remain challenging. UC Berkeley researchers have developed engineered immune cells that produce and intercellularly transfer a protein and/or RNA cargo in response to contact with a predetermined antigen. Proof of concept experiments demonstrated that production of EDVs can be induced in a T cell line through either the presence of a small molecule or recognition by the T cells of a specific antigen on co-cultured cells. The researchers showed that delivery can be achieved using multiple strategies and that the system is compatible with multiple cargo proteins of interest, including Cre recombinase and S.pyogenes Cas9. 

A novel dendronized polypeptide architecture for efficient and safe mRNA delivery, suitable for anti-tumor immunotherapy.

This technology provides methods for synthesizing a group of naturally occurring compounds, syrbactins, and their derivatives, being of significant commercial value due to the ability of some of the members to inhibit proteasomal activity. TIR-199, for example, is one of the most potent proteasome inhibitors synthesized so far. The efficacy and efficiency of this novel drug candidate in inducing tumor cell death in multiple myeloma, neuroblastoma, and other types of cancer (e.g. kidney, colon, melanoma, ovarian) has been demonstrated using in vitro systems, cell lines, and animal models (reported for the first time for a syrbactin compound). TIR-199 drug candidate is ready for further pre-clinical and eventually clinical studies.  

Researchers at the University of California, Davis have developed a technology involving statistically reconstructing positronium (or positron) lifetime imaging (PLI) for use with a positron emission tomography (PET) scanner, to produce images having resolutions better than can be obtained with existing time-of-flight (TOF) systems.

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.

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A groundbreaking discovery of small molecule inhibitors of MAP4K3, potentially transforming therapeutic treatment for neurological diseases and cancer.

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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.

This novel technology enables refined temporal control of protein-protein interactions that can be used to regulate cell therapies, including CAR T-cells and “cell factories”.

High flux (e.g., greater than 1012 n/s/cm2) neutrons with energies between 8 and 30 MeV are needed for a number of applications including radioisotope production. However, none of the existing neutron sources available can fulfill these requirements. Neutron flux intensities from typical neutron sources using Deuterium-Tritium (DT) fusion are typically more than 2 orders of magnitude lower in intensity than what is needed for making production practical. Deuterium-Deuterium (DD) fusion sources provide a spectrum which is too low in energy to perform the nuclear reactions needed for isotope production. High-energy proton accelerator-driven spallation sources produce isotopes with significant co-production of unwanted radioisotopes, due to a neutron spectrum which is far higher in energy than required. While accelerator-driven neutron sources using deuteron breakup have been shown to be a viable pathway for producing a range of isotopes including actinium-225 1, a limited number of machines capable of producing ~30 MeV deuteron beams exist commercially. To address this problem, researchers at UC Berkeley have developed systems and methods for producing radionuclides using accelerator-driven fast neutron sources, and more specifically for producing actinium-225, an inherently-safe, fast neutron source based on low energy proton accelerators used throughout the world to support positron emission tomography.

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