Researchers at the University of California, Davis have identified a short peptide which rapidly promotes protein degradation in cancerous enzymes and induces cell differentiation to kill lymphomas.

Researchers at the University of California, Davis have developed a virally derived homolog to increase the inflammatory response desirable in cancer immunotherapy.

Researchers at the University of California, Davis have developed a viral peptide therapeutic that targets MYC-based cancerous tumors.

Prof. Thomas Kuhlman at the University of California, Riverside has developed a high yield method to scale and purify native, full-length SARS-CoV-2 Membrane (M) protein.  This method may be utilized to scale the production and purification of M protein for research purposes.

Brief description not available

Existing art in modulation of gene expression by nucleic acid targeting mechanisms primarily comprises methods for REDUCING gene expression, e.g. via DNA targeting (CRISPR gene knockout, reduction of transcription via CRISPR-i), or RNA targeting (shRNAs/siRNAs, ASOs, microRNA mimics). ENHANCEMENT of gene expression on the RNA level has been achieved using microRNA inhibitors; however the effects are typically small and are not target-specific (many other microRNA target-RNAs are also upregulated).The molecular functions of the majority of RNA-binding proteins (RBPs) remain unclear, highlighting a major bottleneck to a full understanding of gene expression regulation. 

Researchers at the University of California, Davis have developed a single-use chip for the identification of protein crystals using X-ray based instruments.

Researchers at the University of California, Davis, have developed an environmentally friendly one-pot multienzyme (OPME) method for synthesizing sialidase reagents, probes, and inhibitors.

The inventors have developed two new CasX gene-editing platforms (DpbCasXv2 and PlmCasXv2) through rationale structural engineering of the CasX protein and gRNA, which yield improved in vitro and in vivo behaviors. These platforms dramatically increase DNA cleavage activity and can be used as the basis for further improving CasX tools.The RNA-guided CRISPR-associated (Cas) protein CasX has been reported as a fundamentally distinct, RNA-guided platform compared to Cas9 and Cpf1. Structural studies revealed structural differences within the nucleotide-binding loops of CasX, with a compact protein size less than 1,000 amino acids, and guide RNA (gRNA) scaffold stem. These structural differences affect the active ternary complex assembly, leading to different in vivo and in vitro behaviors of these two enzymes.

Researchers at the University of California, Davis have developed a viral amplicon-based vector system for heterologous protein expression and production in plants.

Researchers at the University of California, Davis have developed a method for preparing a bacterial cell lysate that results in higher protein expression than existing cell-free systems. The new whole-cell lysate system comes with additional advantages, including the ability to synthesize protein from linear DNA, directly amenable to continuous or flow-based reaction, and compatibility with existing manufacturing workflow.

The inventors have developed an enzymatically catalyzed method for simple and rapid coupling of biomolecules to native amino acids on protein surfaces. This method is capable of attaching tyrosine or phenol containing molecules, peptides, or proteins to cystine or thiol containing targets at neutral pH with high yields. The inventors demonstrate the utility of this system by modifying Cas9 and other proteins with fluorophores, peptides, and whole proteins, such as green fluorescent proteins (GFPs) and antibody short chain variable fragments. This technology represents a novel paradigm in biomolecule coupling.

To meet the ever-growing demand for effective, safe, and affordable protein therapeutics, decades of intense efforts have aimed to maximize the quantity and quality of recombinant proteins produced in Chinese hamster ovary (CHO) cells. CHO cells are extensively used to produce biopharmaceuticals and one advantage is their reduced susceptibility to many human virus families. However, there have been a few episodes of animal viral contamination of biopharmaceutical production runs, mostly from trace levels of viruses in raw materials. These infections more often caused by RNA viruses have led to expensive decontamination efforts and threatened the supply of critical drugs. Viral contamination in biopharmaceutical manufacturing can lead to shortages in the supply of critical therapeutics. Therefore there is a need to understand the mechanisms by which CHO cells are infected and how the cells can be universally engineered to enhance their viral resistance.

UCLA researchers in the Department of Bioengineering and Department of Chemistry & Biochemistry have developed a novel method for the introduction of various functional groups onto recombinant elastin-like polypeptides (ELPs), creating new compositions of ELPs that may be used for medical therapeutic or diagnostic applications.

Researchers at the University of California, Davis have developed a microbial culture capable of translating mRNA molecules into a polypeptide with a single reaction mixture.

Inventors at UC Irvine have engineered an orthogonal DNA replication system capable of rapid, accelerated continuous evolution. This system enables the directed evolution of specific biomolecules towards user-defined functions and is applicable to problems of protein, enzyme, and metabolic pathway engineering.

Living bioreactors are powerful systems for producing a variety of valuable compounds. The versatility of such bioreactors is one of the more useful aspects of the system. Large quantities of compounds or cellular components can be produced efficiently, with minimal cost. Alternately, these systems can be used to produce pathway components that are necessary in the production of secondary products. A common problem with such systems is that they are limited by non-uniform production of pathway components, or require an isolation process to ensure the components are in the appropriate quantity and sequence in the process. Inventors at Texas A&M and UC San Francisco have developed a novel technique to address these issues. The technology effectively results in a stoichiometric production of protein components that are produced in an array, ready for secondary production.

UCLA researchers in the Department of Bioengineering and Department of Chemistry & Biochemistry have developed a novel method for efficient, chemoselective transformation of methionines in peptides and polypeptides into stable, functional homocysteine derivatives. This method provides a means of creation of new functional biopolymers, site-specific peptide tagging, and synthesis of biomimetic and structural analogs of peptides.

While current methods for membrane protein functional reconstitution in biomimetic membranes approaches are powerful and have uncovered fundamental properties of protein function, they are methodologically cumbersome, requiring chromatography steps to remove detergents. Moreover, structural features normally found in cell membranes such as curvature and polarity are mostly absent. In this regard, an efficient reconstitution methodology that better mimics the native chemical environment of a whole-cell embedded protein would be highly useful.

Biotherapeutic proteins manufactured in cell culture systems have transformed modern medicine. Selling many tens of billions per year, new biotherapeutics such as monoclonal antibodies have delivered dramatic clinical results, while posing significant manufacturing problems.: During the cell culture manufacturing process, toxic bioproducts such as lactate and ammonia have posed considerable challenges in bioprocessing, since they limit cell growth and impact critical quality attributes of recombinant protein production (e.g., therapeutic drugs, enzymes). That is because the lactate alters the regulation of biosynthetic enzymes, and can lead to changes in pH in the culture. To mitigate the negative effects of lactic acid accumulation and control the culture pH, chemical ‘base’ is added to the media during the course of a bioprocess. However, the base addition negatively impacts the bioprocess by inhibiting growth and shortening the length of time in which the cells can produce the recombinant protein. This leads to reduced yield, and increased cost-of-goods. Thus, it is of great interest to eliminate lactate production, and UC San Diego researchers have recently developed a new process for achieving this.  

Alzheimer’s Disease is a prevalent neurodegenerative disorder affecting 10% of people over age 65. It is characterized by a progressive loss of cognitive function and memory impairments that are associated with increased peptide and protein aggregation in the brain. The invention herein describes a novel therapy for Alzheimer’s Disease which would promote the removal of toxic Amyloid-beta peptides out of the brain.

Protein aggregation in the brain are the causes of the neurodegenerative diseases Alzheimer’s and Parkinson’s. To study diseases and cellular mechanisms, biologists need to be able to efficiently synthesize, isolate and purify proteins. The invention herein is a synthetic nanoparticle (NP) that protects proteins from aggregation at temperatures, which normally cause aggregation. Furthermore, multiple stimuli can release the protein in high yield from the NPs.

The invention is a diagnostic technology, as well as a research and development tool. It is a simple, easy to operate, and effective platform for the analysis of pharmaceuticals and biological species. Specifically, this platform generates hydroxyl radicals for oxidative footprinting – a technique commonly employed in protein mapping and analysis. The platform itself is inexpenisve to fabricate, scalable, and requires nothing more than an ordinary pipet to use. In addition, it is highly amenable to scale-up, multiplexing, and automation, and so it holds promise as a high-throughput method for mapping protein structure in support of product development, validation, and regulatory approval in the protein-based therapeutics industry.

Glycosylation is a key post-translational modification that can affect critical properties of proteins produced in biopharmaceutical manufacturing, such as stability, therapeutic efficacy, or immunogenicity. However, unlike a protein's amino acid sequence, glycosylation is hard to engineer since it does not follow any direct equivalent of a genetic code. Despite various attempts to computationally model the process of glycosylation, industrial glycoengineering is still largely carried out using costly and time-consuming trial-and-error strategies and could greatly benefit from computational models that would better meet the requirements for industrial utilization.

Prof. Xin Ge and his colleagues at the University of California, Riverside have developed a library of human, selective MMP-14 antibody inhibitors with nanomolar activities. Unlike known MMP inhibitors, n-TIMP-2 and GM6001, that inhibit a broad spectrum of the MMP family these antibody inhibitors do not exhibit off-target effects with other MMP family members such as MMP-2/MMP-9. Fig. 1 shows inhibition selectivity tests of Fab 3A2, GM6001 and n-TIMP-2. Unlike n-TIMP-2 and GM6001, Fab3A2 shows selectivity for MMP-14 and did not inhibit MMP-2 or MMP-9.     Fig. 2 shows the weight and number of the pulmonary metastic lesions in B16F1 (Mock) and B16F1 MT-MMP (mMT1) mouse models. The mMT1 mouse model treated with the 3A2 (mMT+3A2) antibody showed a reduction in the weight and number of pulmonary metastatic lesions.