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Researchers at UC Irvine have developed methods to facilitate the delivery of a high dose, low energy electron beam or X-ray in a compact manner.

Researchers at UC Irvine have developed an optical detection system for SARS-CoV-2 and other pathogens that features improvements in screening time, cost, sensitivity, and practicality. As vaccine availability, economic pressure, and mental health considerations has gradually returned society to pre-pandemic activities that require frequent and close interactions, it is imperative that SARS-CoV-2 detection systems remain effective.

Researchers at UC Irvine have developed a novel algorithm that more accurately filters raw blood pressure (BP) data collected from continuous non-invasive blood pressure sensors. The algorithm features improvements in eliminating baseline signal drift while maintaining signal integrity and BP estimation accuracy across significant hemodynamic changes.

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Researchers at UC San Diego have developed a dipeptide composed of two arginine (Arg-Arg) that is capable of inducing the assembly of citrate-capped gold nanoparticles (AuNPs-citrate). Surprisingly, the resulting Arg-Arg-AuNPs are stable over time as the peptide protects the particles from degradation. The assemblies can even be dried without any loss of particles. The assembly of AuNPs-citrate changes their optical properties and the color of the suspension turns from red to blue. Importantly, the assemblies can be dissociated with thiolated polyethylene glycol (HS-PEGs) molecules which leads to the recovery of the initial optical properties of the AuNPs, i.e. the red color of the suspension. Surprisingly, we have observed that such dissociation of AuNPs assemblies is not sensitive to the composition of the medium. It can thus be performed in biological fluids such as pure plasma, saliva, urine, bile, cell lysates or even sea water.

Scientists at UCSF have developed a novel class of BCR-ABL inhibitors that engages two binding sites in BCR-ABL simultaneously. This two-site binding (bitopic) mechanism of action is unprecedented against BCR-ABL, one of the most well-validated targets in oncology.

Long read nanopore sequencing can directly sequence RNA molecules, including rRNA, and result in full-length RNA sequences. rRNA sequencing is particularly useful for identifying microbes and full-length rRNA sequencing can identify microbes with post transcriptional modifications that confer antibiotic resistance. Such post transcriptional modifications are invisible to amplification based sequencing or other sequencing techniques that require reverse transcription.Before this technology was developed, there were few if any efficient methods for preparing rRNA libraries for direct RNA sequencing, particularly for microbial identification in either a clinical or an environmental setting.   

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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 the University of California, Davis have developed a customizable polysaccharide that can be added to nanoparticles to reduce their rejection by the human immune system.

The function of living tissue relies not only on its structure, but crucially on its dynamics at an array of timescales. Structural imaging of biological molecules at very high resolution has become routine in recent years, but these static snapshots provide little insight into the structural changes crucial for biological function. It is well known that changes in the geometry of macromolecules induce fluctuations in the Raman spectrum, but measurements of these fluctuations inherently suffer from poor signal strengths, meaning that dynamics at many timescales are obscured by the time-averaging necessary to obtain sufficient sensitivity.To address these problems, researchers at UC Berkeley have developed a method for probing the Raman spectrum, and hence dynamics of biological molecules at very high sensitivity and across timescales inaccessible to extant techniques. This technique, in fact, can in principle obtain arbitrarily fine spectral and temporal resolution, opening the door to, for example, probe everything from the dynamics of side chain rotations (picoseconds) to protein folding and domain motion (milliseconds).

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.

Vaccine design is at the forefront of therapeutic development. Candidate proteins for recombinant vaccine design are expressed as soluble proteins lacking the native transmembrane domain. These proteins are often fused with multimerization domains to stabilize the native oligomeric state of the candidate protein. However, these multimerization domains can elicit off-target immune responses, raising concerns regarding risks of unintended immunogenicity. Thus, there is a need to eliminate potential off-target effects of recombinant vaccine candidates that contain multimerization domains such as the foldon domain.

Researchers at the University of California, Davis, have developed a novel approach to treat hearing-related disorders with a new type of psychoplastogen that can increase the synapse density in the ear, correlating with hearing ability.

Cardiovascular disease is among the leading causes of death for citizens in affluent nations, and the most significant cause of morbidity in those with cardiovascular disease is hypertension. Often called the “silent killer” because it has few clinical signs in its early stages, elevated blood pressure is often in an advanced stage before it is treated, leading to a substantially worse prognosis than if it had been detected earlier.In order to address this problem, researchers at UC Berkeley have developed a wearable device which continuously monitors diastolic blood pressure, transmitting data to a portable device such as a cell phone, where it can be stored and analyzed. The device utilizes piezoelectric transducers to perform the measurement, which allows the wearable device to remain small while containing a large number of sensors in order to reduce noise.

Researchers at the University of California, Davis have developed a method to stop bacterial growth while maintaining desirable metabolic functions for therapeutic and biotechnological applications.

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 (CSPG4 and FZD) which compete for TcdB binding, significantly improving upon existing antibody therapeutics for Clostridium difficile infections.

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Researchers at the University of California, Davis have developed a targeted epigenetic approach for the prevention and treatment CDKL5 deficiency disorder.

There are no approved disease-modifying therapies for Huntington’s disease (HD), a fatal neurodegenerative condition caused by a heterozygous expansion of a CAG array in exon 1 of Huntingtin (Htt). Typically, HD patients are heterozygous for the toxic gain of function disease allele, yet expression of the wildtype version of the gene is essential. The inventors have developed methods and compositions to selectively silence expression from the disease-associated allele while leaving the wildtype version intact. The invention relies on the introduction of a 'poison' exon into the diseased allele wherein introduction of the poison exon may be accomplished by standard methods in the art, such as introduction of the exon sequences through homology-directed repair following targeted nuclease cleavage, transposon-associated targeted sequence introduction, base editing, and prime editing. Following the introduction of the poison exon, post-transcriptional splicing results in an RNA that is susceptible to nonsense mediated decay due to the introduction of a stop codon in the introduced exon. RNAs comprising the poison exon are subsequently degraded in the cell, effectively silencing expression of the mutant disease-associated allele.

Methyl-CpG-binding-protein 2 (MeCP2) is a nuclear protein expressed in all cell types, especially neurons. Mutations in the MECP2 gene cause Rett syndrome (RTT), an incurable neurological disorder that disproportionately affects young girls. Strategies to restore MeCP2 expression phenotypically reverse RTT-like symptoms in male and female MeCP2-deficient mice, suggesting that direct nuclear delivery of functional MeCP2 could restore MeCP2 activity.The inventors have discovered that ZF-tMeCP2, a conjugate of MeCP2(aa13-71, 313-484) and the cell-permeant mini-protein ZF5.3, binds DNA in a methylation-dependent manner and reaches the nucleus of model cell lines intact at concentrations above 700 nM. When delivered to live cells, ZF-tMeCP2 engages the NCoR/SMRT co-repressor complex and selectively represses transcription from methylated promoters. Efficient nuclear delivery of ZF-tMeCP2 relies on a unique endosomal escape portal provided by HOPS-dependent endosomal fusion.In a comparative evaluation, the inventors observed the Tat conjugate of MeCP2 (Tat-tMeCP2) (1) degrades within the nucleus, (2) is not selective for methylated promoters, and (3) traffics in a HOPS-independent manner. These results support the feasibility of a HOPS-dependent portal for delivering functional macromolecules to the cell interior using the cell-penetrant mini-protein ZF5.3. Such a strategy could broaden the impact of multiple families of protein-derived therapeutics.

Type III CRISPR-Cas systems recognize and degrade RNA molecules using an RNA-guided mechanism that occurs widely in microbes for adaptive immunity against viruses. The inventors have demonstrated that this multi-protein system can be leveraged for programmable RNA knockdown of both nuclear and cytoplasmic transcripts in mammalian cells. Using single-vector delivery of the S. thermophilus Csm complex, RNA knockdown was achieved with high efficiency (90-99%) and minimal off-targets, outperforming existing technologies of shRNA- and Cas13-mediated knockdown. Furthermore, unlike Cas13, Csm is devoid of trans-cleavage activity and thus does not induce non-specific transcriptome-wide degradation and cytotoxicity. Catalytically inactivated Csm can also be used for programmable RNA-binding, which the inventors exploit for live-cell RNA imaging. This work demonstrates the feasibility and efficacy of multi-subunit CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes.