Researchers at UCSF have developed XYZeq, a method for coupling a cell’s spatial location with single-cell sequencing. Single-cell genomic techniques have emerged as powerful approaches to further our understanding of disease states and cellular heterogeneity. Single-cell imaging methods gain spatial information, but lack throughput and detailed transcriptomic information. Current single-cell sequencing approaches require dissociation of cells during preparation, as a result cannot record a cell’s physical location. UCSF researchers eliminate this step using XYZeq, a new scRNA-seq process that incorporates the benefits of single-cell imaging techniques with single-cell sequencing, without an imaging step. XYZeq simultaneously discerns the location and gene expression of a single cell residing within a complex tissue microenvironment. The technology has been validated in a laboratory setting.

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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.

The present invention features a device for rapidly formatting a chemical compound library into microfluidic droplets, addressing the challenge of interfacing between the macroscale and the microscale regimes of the production of reagent libraries of chemical compounds.

The present invention features a method and device that addresses the need for a low-cost and easy-to-use method and device to pattern a sharp interface between two or more cell populations or, more generally, two or more coatings wherein their interfacing properties are of interest. As a result, the present invention enables new types of experiments that analyze cell-cell interactions and the study of tissue biology in general. 

The invention is an integrated device that provides a high efficiency single cell encapsulation solution. The two core modules of the invention are responsible for generating the cell encapsulating droplet, then sorting the generated droplets to eliminate the empty ones. Such a two-step process yields a high throughput, single cell indexed droplets, with an overall encapsulation efficiency reaching 80%, which is crucial for various applications ranging from genomics and proteomics to pharmacology.

Common drug screen models, such as animals and 2D cell cultures, do not properly recapitulate human organ structure and environment. Using 3D bioprinting technology, researchers at UCI have developed all-inclusive customized organ-on-a-chip-like platforms. These platforms produce cell models that properly mimic the microenvironment of cells for drug screening and cell-therapeutic response studies.

Researchers at UCI have developed an imaging technique that can monitor and measure small mobile structures called cilia in our airways and in the oviduct. This invention will serve as a stepping stone for study of respiratory diseases, oviduct ciliary colonoscopy and future clinical translations.

Researchers at UCI have developed a novel microfluidic-based platform that enables personalized drug screening of patient-derived cancer cells. This versatile device features real-time, continuous screening of patient samples without the need for expensive labeling reagents, large sample sizes, or bulky readout equipment.

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.

Molecular self-assembly with scaffolded DNA origami offers a route for folding nucleic acid molecules in user-defined ways, to generate DNA nanostructures. DNA nanostructures have a single-stranded DNA that is folded into distinct shapes via oligonucleotides termed “staples.” Engineered nuclease systems can be used to cleave a target DNA at a specified location. Examples of engineered nuclease systems include TALENs, zinc finger nucleases, mega-nucleases, and CRISPR-Cas systems. Introduction of a break in a nucleic acid (e.g. genome) can facilitate the introduction of a donor nucleic acid.    UC Berkeley researchers have discovered compositions comprising a gene-editing polypeptide, a single-stranded donor DNA, and one or more staple oligonucleotides which can be used for gene editing. 

This invention leverages the nuclease activity of CRISPR proteins for the direct, sensitive detection of specific nucleic acid sequences. This all-in-one detection modality includes an internal Nuclease Chain Reaction (NCR), which possesses an amplifying, feed-forward loop to generate an exponential signal upon detection of a target nucleic acid.Cas13 or Cas12 enzymes can be programmed with a guide RNA that recognizes a desired target sequence, activating a non-specific RNase or DNase activity. This can be used to release a detectable label. On its own, this approach is inherently limited in sensitivity and current methods require an amplification of genetic material before CRISPR-base detection. 

Viral infection is a multistep process involving complex interplay between viral life cycle and host immunity. One defense mechanism that hosts use to protect cells against the virus are nucleic-acid-mediated surveillance systems, such as RNA interference-driven gene silencing and CRISPR-Cas mediated gene editing. Another important stage for host cells to combat virus replication is translational regulation, which is particular important for the life cycle of RNA viruses, such as Hepatitis C virus and Coronavirus.  While efforts to characterize structural features of viral RNA have led to a better understanding of translational regulation, no systematical approaches to identify important host genes for controlling viral translation have been developed and little is known about how to regulate host-virus translational interaction to prevent and treat infections caused by RNA viruses.   UC Berkeley researchers have developed a high-throughput platform using CRISPR-based target interrogation to identify new therapeutics targets or repurposed drug targets for blocking viral RNA translation.  The new kits can also be used to identify important domains within target proteins that are required for regulating (viral RNA translation) and can inform drug design and development for treating RNA viruses.

Researchers at the University of California, Davis have developed a robotic dispensing interface that uses a microfluidic-embedded container cap – often referred to as a microfluidic Cap-to-Dispense or μCD - to seamlessly integrate robotic operations into precision liquids handling.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. It can be broadly sub-classified into nonalcoholic fatty liver (NAFL), which is thought to have minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), which is thought to have an increased risk of progression to cirrhosis. The current diagnostic gold standard for differentiating whether a patient with NAFLD has NAFL versus NASH is liver biopsy. However, liver biopsy is an invasive procedure, which is limited by sampling variability, cost, and may be complicated by morbidity and even death, although rare. Accurate, non-invasive, biomarkers for the detection of liver disease and liver disease progression e.g., progression to NASH, are currently also not available.

In this invention, the HNH domain of a Cas9 is replaced by a domain that could have diverse enzymatic activities. This invention enables engineering of Cas9 chimeras that possess novel, conformation-sensitive enzymatic activity to perform specific genome editing in vitro, in vivo, and ex vivo.Prior to this invention, all of the strategies to engineer Cas9 fusion proteins and provide Cas9 with non-natural enzymatic activity for genome manipulations were engineered by fusing specific domains to the N- or C-terminus of Cas9 via long and flexible linkers, or through domain insertion approach. The disadvantages of these synthetic Cas9 chimeras are that the attached domain is on the long flexible linker, and it is very dynamic. Thus, these fusions have a broad activity window and they are large, which makes it difficult to deliver them to the cells. 

Researchers at the University of California, Davis have developed monoclonal antibodies with multiple applications relevant to canine PD-1 and PD-L1.

UCLA researchers in the Departments of Bioengineering and Head & Neck Surgery have developed a novel robotic platform for the training of transoral surgery.

Cardiovascular disease (CVD) is a tremendous burden on the population in terms of morbidity and mortality, as well as on the healthcare system in terms of cost. Various forms of CVD including atherosclerosis, valve and ventricular dysfunction, aneurysms, and thrombogenesis can be identified by measuring localized abnormalities in blood flow. Accordingly, the ability to noninvasively interrogate physiological flows enables identification and diagnosis of disease, monitoring of the effects of therapy, and research on the hemodynamic nature of CVD and its associated interventions. In the clinic, blood flow measurements are primarily made using phase contrast magnetic resonance imaging (PC-MRI) and ultrasonic color Doppler imaging. Certain limitations of these techniques for patients who have contraindications or suffer from arrhythmias, as well as the desire for volumetric flow information necessitate the development of a new modality for blood flow velocimetry.

Constructing antibody repertoires is an important error-correcting step in analyzing immunosequencing datasets that is important for reconstructing evolutionary (clonal) development of antibodies. However, the state-of-the-art repertoire construction tools typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction. Thus, although repertoire construction is a prerequisite for follow up clonal tree reconstruction, the existing repertoire reconstruction algorithms are not well suited for this task because they typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction.

Autism Spectrum Disorder (ASD) is a developmental disorder associated with difficulties in social interaction and communication as well as repetitive behavior. ASD is thought to be the result of genetic and environmental factors that affect approximately 1 in 59 children in the US, and 25 million people worldwide. The current method of diagnosis for ASD involves evaluations and tests performed by a team of specialists.  The latest forms of diagnosis can detect ASD as early as 18 months. However, more standard methods take until 4 years of age before the diagnosis of ASD is confirmed. There remains an unmet need to develop a reliable and accurate diagnostic methods for early detection for a child at risk with chronic and/or developmental disorders, such as ASD, so that an early intervention measures will be applied before the first symptoms appear.

Prof. Min Xue and his colleague at the University of California, Riverside have developed peptide-based selective MMP-2 inhibitors with nanomolar activities. Unlike known MMP inhibitors, n-TIMP-2 and GM6001 that inhibit a broad spectrum of the MMP family, these peptide inhibitors do not exhibit off-target effects with other MMP family members such as MMP-9.  Fig. 1 shows how a proMMP2 inhibitor (orange) interferes with the protein-protein interaction (PPI) between proMMP2 and TIMP2 (tissue inhibitor of metalloproteinases 2). This PPI inhibition blocks the TIMP2-assisted proMMP2 activation process and thereby results in lower levels of active MMP2. Fig. 2 shows the novel UCR MMP-2 peptide binds to proMMP2 with an Kd of 2.3 nM and inhibits MMP2 activation with an IC50 of 20 nM.  

Brief description not available

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a Compliant Membrane Acoustic Patterning (CAMP) technology capable of patterning cells in an arbitrary pattern at a high resolution over a large area.

UCLA researchers in the Department of Electrical & Computer Engineering have designed and built a computational cytometer capable of detecting rare cells at low concentration in whole blood samples. This technique and instrumentation can be used for cancer metastasis detection, immune response characterization and many other biomedical applications.