Various plasmids from Michael Rape's lab, including but not limited to:pQE-UbcH5c/pET-Ube2D3-6xHispET28-E2NpET28-UEV1ApET28a-UBE2S-6xHISpET28a-E2R1-6xHIS 

Various ubiquitin plasmids from Michael Rape lab, including but not limited to: pCS2-no his-ubiquitin wtpCS2-no his-ubiquitin all RpET30a-ubiquitin (no tag)pET30a-ubiquitin K0 (no tag) 

Dysfluent speech modeling requires time-accurate and silence-aware transcription at both the word-level and phonetic-level. However, current research in dysfluency modeling primarily focuses on either transcription or detection, and the performance of each aspect remains limited.To address this problem, UC Berkeley researchers have developed a new unconstrained dysfluency modeling (UDM) approach that addresses both transcription and detection in an automatic and hierarchical manner. Furthermore, a simulated dysfluent dataset called VCTK++ enhances the capabilities of UDM in phonetic transcription. The effectiveness and robustness of UDM in both transcription and detection tasks has been demonstrated experimentally.UDM eliminates the need for extensive manual annotation by providing a comprehensive solution.

Various plasmid constructs and cell lines for E3 Ligase project from Julia Schaletzky lab, including but not limited to:  pET28-ubiquitin wtpET28-ubiquitin deltaGGpLentiX1hygropLentiX1 blastpLentiX1 puropLentiX1 neopCS2-6xHIS-Htt-73QpCS2-6xHIS-Htt-23QpInducer Htt-23Q-GFPpInducer Htt-73Q-GFP

Listeria monocytogenes has been used as a therapeutic vaccine in more than 20 cancer clinical trials and administered to more than 1800 patients. However, Listeria monocytogenes vaccines have been less immunogenic in clinical trials. In rare cases, live bacteria were found in patients’ blood or on implants, after the administration of live vaccines. Additionally, even attenuated vaccine strains still caused severe adverse events and consequently put clinical trials on hold. Due, in part, to the safety and efficacy concerns of using Listeria monocytogenes as a live vector for cancer immunotherapy, there is a need for safer and more potent strains of Listeria monocytogenes.  UC Berkeley researchers have created a Listeria monocytogenes mutant strain that will likely be a safer and potentially more potent platform for the future development of cancer therapeutics. The strain is auxotrophic for adenosine, a purine nucleoside with extremely low levels in blood and healthy cells. The strain cannot grow in the host cell cytosol and is significantly attenuated in the mouse infection model. The improvement in the safety of this invention is further demonstrated by the poor growth of the mutant strain in host extracellular environments such as mouse gallbladders and human blood. Although attenuated, the invented strain elicits a robust effector CD8+ T cell response in mice and protects mice against lethal-dose challenges of wild-type L. monocytogenes. More importantly, the immunogenicity of this invention is more potent in mice than in previous Listeria monocytogenes vaccine strains. Another facet of this invention is that because of the high concentration of adenosine in tumor microenvironments, the mutant strain could potentially survive and multiply in tumors.  

A primary reason behind the lack of progress in heart therapeutics is the inability to use phenotypic human tissue-level approaches to discover novel therapies. In recent years, there have been significant advances in the development microphysiological systems (MPS), which recapitulate organ-level and even organism-level functions.   MPS are quickly becoming representative of the future of disease modeling and drug screening, therefore paving the way for complex in vitro models to dominate the preclinical drug discovery landscape. However, there has yet to be an effective LNP formulation for therapeutic mRNA delivery to the heart. Therefore, despite progress in this area, one of the remaining challenges is to develop a LNP formulation capable of diffusing within human cardiac muscle, transfecting cardiomyocytes, and escaping the endo-lysosome before degradation more efficiently than current strategies. UC Berkeley researchers and others have developed compositions and methods using lipid nanoparticles for delivery of a payload (e.g., messenger RNA (mRNA)) to the heart, for delivery of mRNA for transfection of cells and methods of treatment.

Delivery technologies such as lipid nanoparticles (LNP) offer significant advantages over the delivery of free RNA for various RNA therapeutic, vaccine, and basic science applications. UC Berkeley researchers developed a new class of lipid nanoparticle (LNP) which is effective in delivering various types of nuclei acids in different tissues.  The LNP was successfully tested in in-vivo mouse models and therefore poses a significant promise in the gene editing field. The lipid formulation was packaged together with CRISPR Cas9 and a gRNA targeting the endogenous Tau locus. Tau dysrregulation is a pathological feature of Alzheimers disease, thus the invention provides a means to intervene in the development of pathological states associated with Tau aggregate formation. 

There are 118 known elements. Nearly all of them have NMR active isotopes and at least 39 different nuclei have been shown to have biological relevance. Despite this, most of today’s MRI is based on only one nucleus – 1H. To work towards making use of all potential nuclei, here, UC Berkeley researchers have created a coil enabling the excitation of arbitrary nuclei in human-scale MRI with a single coil. To excite arbitrary nuclei, they developed a completely new type of RF coil, the Any-nuclei Distributed Active Programmable Transmit Coil (ADAPT Coil), that can operate at any relevant frequency. This coil eliminates the need of the expensive traditional RF amplifier by directly converting DC power into RF magnetic fields with frequencies chosen by digital control signals sent to the switches. Semiconductor switch imperfections are overcome by breaking the coil into several segments. The ADAPT Coil presents a scalable and efficient method of exciting arbitrary nuclei in human-scale MRI. This coil concept provides further opportunities for scaling, programmability, lowering coil costs, lowering dead-time, reducing multinuclear MRI workflow complexity, and enabling the study of dozens of biologically relevant nuclei.  

Volumetric additive manufacturing and vat-polymerization 3D printing methods rapidly solidify freeform objects via photopolymerization, but problematically raises the local temperature in addition to degree-of-conversion (DOC). The generated heat can critically affect the printing process as it can auto-accelerate the polymerization reaction, trigger convection flows, and cause optical aberrations. Therefore, temperature measurement alongside conversion state monitoring is crucial for devising mitigation strategies and implementing process control. Traditional infrared imaging suffers from multiple drawbacks such as limited transmission of measurement signal, material-dependent absorptions, and high background signals emitted by other objects. Consequently, a viable temperature and DOC monitoring method for volumetric 3D printing doesn’t exist.To address this opportunity, UC Berkeley researchers have developed a tomographic imaging technique that detects the spatiotemporal evolution of temperature and DOC during volumetric printing. The invention lays foundations for the development of volumetric measurement systems that uniquely resolve both temperature and DOC in volumetric printing.This novel Berkeley measurement system is envisaged as an integral tool for existing manufacturing technologies, such as computed axial lithography (CAL, Tech ID #28754), and as a new research tool for commercial biomanufacturing, general fluid dynamics, and more.

UC Berkeley researchers have developed variant Listeria bacteria that have one or more  nucleic acids that encode polypeptides required for isoprenoid synthesis through the non-mevalonate pathway, wherein the Listeria bacterium grows aerobically in the presence or absence of a functional mevalonate pathway. The Listeria strain can be used to induce enhanced activation and expansion of human gamma delta T-cells and have been shown to do so in vitro.  

Hyperspectral imaging, the practice of capturing detailed spectral (color) information from the output of an optical instrument such as a microscope or telescope, is useful in biological and astronomical research and in manufacturing. In addition to being bulky and expensive, existing hyperspectral imagers typically require scanning across a specimen, limiting temporal resolution and preventing dynamic objects from being effectively imaged. Snapshot methods which eliminate scanning are limited by a tradeoff between spatial and spectral resolution.In order to address these problems, researchers at UC Berkeley have developed a hyperspectral imager which can be attached to the output of any benchtop microscope. The imager is compact (about 6-inches), and can achieve a higher spatial resolution than traditional snapshot imagers. Additionally, this imager needs only one exposure to collect measurements for an arbitrary number of spectral filters, giving it unprecedented spectral resolution.

Rhamnolipids (RLs) are a class of bacterially produced biosurfactants that possess antimicrobial as well as surface-active properties. While RLs have broad utility in industry as antimicrobial biosurfactants, their anionic nature limits the efficacy of these molecules in certain applications. Alternatively, rhamnolipid esters (RLEs) exhibit improved properties as nonionic surfactants. However, a major challenge in RLE application in the commercial arena is that, to date, they are only reliably accessed via chemical synthesis, a costly and unsustainable approach.To address this problem, UC Berkeley researchers have developed a novel, reliable microbial source for biosynthesized RLEs enabling their production in an efficient, sustainable, and renewable manner. Additionally, three novel rhamnolipid methyl ester (RLME) congeners have been produced and a new enzyme for RLE production identified. The produced RLEs are expected to be more effective than RLs in many ways, including antifungal activity and hydrocarbon solubilization.

Cardiovascular disease is the leading cause of death both worldwide and in the United States, with associated costs in the U.S. reaching approximately $229 billion, each, in 2017 and 2018. Early detection, which can drastically reduce both rates of death and treatment costs, requires access to facilities and highly-trained physicians that can be difficult to access in rural areas and developing countries—despite their prevalence of cardiovascular disease. Computer-based models that use, e.g., PCG (phonocardiogram), EKG (electrocardiogram), or other cardiac data, are a promising route to bridge the gap in standard-of-care for these underserved areas. However, current algorithms are unable to account for demographic features, such as race, sex, or other characteristics, which are known to affect both the structure of the heart and presentation of heart disease. To address this problem, UC Berkeley researchers have developed a new, cloud-based system for collecting a patient's continuous cardiovascular data, monitoring for and detecting disease, and keeping a doctor informed about the cardiac health of the patient. The system sends an alarm when disease or heart attack are detected. To generate the most accurate diagnoses by taking into account demographic information, the system includes private and ethical dataset collection and model-training techniques.

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.

RNA-mediated adaptive immune systems in bacteria and archaea rely on Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) genomic loci and CRISPR associated (Cas) proteins that function together to provide protection from invading viruses and plasmids. Genome editing can be carried out using a CRISPR-Cas system comprising a CRISPR-Cas effector polypeptide and a guide nucleic acid, such as a guide RNA. However, unintended chromosomal abnormalities following on-target genome editing, such as chromosome loss, are potential concerns for genome editing. UC Berkeley researchers and others have developed a method to modulate the expression levels of the DNA damage response factor p53 in order to mitigate chromosomal abnormalities that occur after genome editing by nucleases like Cas9. The invention provides treatment methods by generating a modified cell and then administering the modified cell to an individual in need thereof and compositions having a CRISPR-Cas effector polypeptide, a guide nucleic acid, and an agent that increases the level of a p53 polypeptide in a mammalian cell.

Researchers at UCSF and UC Berkeley have developed a recombinant adeno-associated virus (rAAV) with an altered capsid protein, where the rAAV exhibits greater ability to infect a central nervous system cell compared to wild-type AAVs. The central nervous system (CNS) comprises a multitude of cell types with diverse functionality and specialization. Dysregulation of neuronal or glial (including microglial) populations has been implicated in multiple disorders, including Alzheimer’s, Parkinson’s, Multiple Sclerosis and Huntington’s disease. AAVs hold tremendous promise as a gene delivery vector to treat such conditions given their reasonable starting efficiency and safety profile. However, challenges in efficient and targeted delivery to specific cell populations make strategies employing these vectors in the CNS particularly challenging. Stage of Research The inventors have developed a recombinant AAV with an altered capsid protein, where the rAAV exhibits greater ability to infect a CNS cell compared to wild-type AAV.

Gut microbiomes play central roles in health and disease. For example, the early-life gut microbiome is a simple yet rapidly changing ecosystem crucial for infant development. Early-life events, such as feeding, influence the succession of the gut microbiome. Breast milk is considered the preferred food source for infants due to its protection against infections and allergy development, among other benefits.  It remains unknown how to best recover a healthy microbiome following disturbance.  UC Berkeley researchers have developed a method of generating an in vitro microbiome that allows the discovery of treatments that enable recovery of infant gut microbiomes from a dysbiotic state. The invention provides the advantage of finding personalized treatments, thus minimizing side effects. A novel component is the use of microbial genome editing to eliminate specific microbial strains or to modify the capacities of specific members of personalized microbiomes to improve their performance or to eliminate pathogenicity factors. This will increase the chances of successful microbiome manipulation compared to more disruptive treatments, such as antibiotics or addition of organisms not normally resident in the native microbiome (e.g., probiotics).

DP-L4056 is a prophage-cured strain of Listeria monocytogenes based on wild-type strain 10403S. A prophage is a bacteriophage genome that is integrated into a bacterial genome. It remains latent until activation by an external factor, and activation leads to production of new bacteriophage particles that lyse the bacterial cell and spread. Curing the prophages in Listeria monocytogenes strain 10403S, which is ubiquitous in the microbiology community as a wild-type reference strain, allows for more predictable engineering and performance of Listeria monocytogenes.

Biological fluids are complex, with compositions that vary constantly and evade molecular definition. Nevertheless, within these fluids proteins fluctuate, fold, function, and evolve as programmed. Synthetic heteropolymers capable of emulating such interactions would replicate how proteins behave in biological fluids, individually and collectively, leading the way toward synthetic biological fluids. However, while there exist known monomeric sequence requirements, the chemical and sequence characteristics of proteins at the segmental level, rather than the monomeric level, may be the key factor governing how proteins transiently interact with neighboring molecules (and how biological fluids collectively behave). To address this opportunity, UC Berkeley researchers have developed a new process of heteropolymer design for protein stabilization and synthetic mimics of biological fluids. The process leverages chemical characteristics and sequential arrangements along protein chains at the segmental level to design heteropolymer ensembles as mixtures of disordered, partially folded, and folded proteins. In studies, for each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids, including: assisting protein folding during translation; preserving the viability of fetal bovine serum without refrigeration; enhancing the thermal stability of proteins; and, behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability.

Positron emission tomography (PET) scanners map the metabolic or biochemical function of tissues by detecting the gamma radiation released by the decay of radioactive tracers ingested by a patient. This technology is particularly useful for mapping tumors because one can devise tracers which tumor cells uptake preferentially. Current gamma radiation detectors are expensive and inefficient, requiring large integration times and radionuclide doses for meaningful image quality. Additionally, the spatial resolution of the resulting map is limited by detector latency, which for traditional technology is 200-500 picoseconds.To address these problems, researchers at UC Berkeley have developed a novel gamma radiation detector with much greater time resolution (potentially down to 10 picoseconds), and higher efficiency (nearly all gamma rays successfully detected). Additionally, these detectors use well-established nanotechnology manufacturing methods and can be produced an order of magnitude more cheaply than existing detectors. The high efficiency of these detectors allows amounts of radioactive tracer used to be decreased by an order of magnitude and spatial resolution to be increased by an order of magnitude when compared to traditional methods.

Measurement of electrical activity in nervous tissue has many applications in medicine, but the implantation of a large number of sensors is traditionally very risky and costly. Devices must be large due to their necessary complexity and power requirements, driving up the risk further and discouraging adoption. To address these problems, researchers at UC Berkeley have developed devices and methods to allow small, very simple and power-efficient sensors to transmit information by backscatter feedback. That is, a much more complex and powerful external interrogator sends an electromagnetic or ultrasound signal, which is modulated by the sensor nodes and reflected back to the interrogator. Machine learning algorithms are then able to map the reflected signals to nervous activity. The asymmetric nature of this process allows most of the complexity to be offloaded to the external interrogator, which is not subject to the same constraints as implanted devices. This allows for larger networks of nodes which can generate higher resolution data at lower risks and costs than existing devices.

This invention are inhibitory nucleic acids, compositions comprising the inhibitory nucleic acids, and methods of using the inhibitory nucleic acids to treat carcinomas.

Existing screening tools for respiratory pathogens, including PCR-based methods and antibody-based methods, are generally time-consuming to perform and analyze, difficult to manufacture at scale, and reliant on a detailed understanding of the targeted pathogen. Additionally, these traditional methods give little insight into the extent to which an individual is capable of spreading the disease. All of these features hamstring early responses to emerging pathogens and early-stage epidemics, as can be seen from the ongoing SARS-COV-2 pandemic. To address these problems, researchers at UC Berkeley have developed a device which ionizes large biomolecules from aerosol droplets and routes them to the inlet of a mass spectrometer or ion mobility spectrometer for identification based on size and/or mass. This can serve as the basis for a screening tool which measures the concentration of pathogenic particles, including common respiratory viruses and bacteria, in the breath. Results from this test could be read out in a matter of seconds, and it does not depend on detailed knowledge of the pathogen in question. Researchers have demonstrated the efficacy of such a device in detecting both large human proteins and virus-sized styrofoam particles.

Viruses have caused substantial health problems in the world. In 2019, the ravage caused by SARS-CoV-2 highlights the global health danger of emergent pathogens again. Rapid diagnostics of viruses is essential for timely, frequently life-saving treatment.  Rapid diagnostics of viruses is essential for timely, and frequently life-saving, treatment. However, most diagnostic testing methods are only capable of detecting single species of virus. In addition, viruses can mutate rapidly, a process which can render single-target diagnostics ineffective. UC Berkeley researchers have developed synthetic DNA arrays as a universal platform to bind viruses with multivalent aptamers which is more tolerant to mutations and capable of detecting multiple species of viruses simultaneously.

BACKGROUND: Triacetic acid lactone (TAL) is an important building block for a diverse set of chemicals and plastic polymers. Native pathways using microbes can serve as an environmentally-friendly and renewable source of TAL production. However, microbial production of TAL is limited to a few platform microbes. Further, native pathways using platform microbes such as E. coli show toxicity to TAL, which reduces its production. Therefore, there is a need for thiolases that provide higher yield and can be used in additional microorganisms. TECHNOLOGY OVERVIEW: Researchers at the Joint BioEnergy Institute (JBEI) have discovered novel thiolases for production of Triacetic acid lactone (TAL) via platform microorganisms. The discovered thiolases achieved production of 2.77 g/L of TAL when expressed in E. coli, which is the highest titer production reported using E. coli. The discovered thiolases were identified from homologs of Cupriavidus necator, and their TAL production was verified by in vitro and in vivo testing. Unlike the energetically expensive native TAL-producing enzyme 2-pyrone synthase, the discovered thiolases utilize acetyl-CoA instead of malonyl-CoA as an extension unit. The Burkholderia thiolases identified by the researchers can be engineered to further boost production of TAL in existing platform microorganisms such as E. coli, as well as other microorganisms such as yeasts. DEVELOPMENT STAGE: Validated system