Researchers at the University of California, Davis have developed a self-assembling, fibrous photosensitizer that targets mitochondria in tumor cells for destruction via photodynamic therapy with enhanced localization and potency.

Researchers from UC San Diego have invented a new form of materials, polymer-integrated crystals (PIX), which combine the structural order of protein crystals with the dynamic, stimuli-responsive properties of synthetic polymers. The inventors have shown that the crystallinity, flexibility, and chemical tunability of PIX can be exploited to encapsulate guest proteins with high loading efficiencies. And, the electrostatic host-guest interactions enable reversible, pH-controlled uptake/release of guest proteins as well as the mutual stabilization of the host and the guest, thus creating a uniquely synergistic platform toward the development of functional biomaterials and the controlled delivery of biological macromolecules.

Professor Min Xue and his lab at the University of California, Riverside have developed a novel hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge that may be used for drug delivery purposes. This peptide is non-toxic and has been shown to transport a wide array of small-molecule cargos into a diverse panel of cells. It enables oral administration and absorption through the intestinal lining, and crosses the BBB in vivo. UCR EPP6 is advantageous over existing technologies since it is nontoxic, efficiently enables oral absorption and transport across the BBB.  Fig 1: A) Structure of the UCR EPP. B) Confocal images showing that EPP6 was able to transport different cargo molecules into the cells. C) Orally administered EPP6 is absorbed by the intestines, entering the blood circulation and reaching the brain.  

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.

Although hematopoietic stem cells (HSCs) are useful in a variety of treatments, HSC donation is a difficult procedure. The original transplantation is commonly extracted from the bone marrow manually, a long and potentially painful procedure. UC Santa Cruz researchers developed a treatment that allows collection of HSC from blood in a 2-hour treatment using already FDA-approved drugs. This makes both the cost and overall comfort of patient donating HSC’s significantly easier.

A major bottleneck in nanocarrier and macromolecule development for therapeutic delivery is our limited understanding of the processes involved in their uptake into target cells. This includes their active interactions with membrane transporters that co-ordinate cellular uptake and processing. Current strategies to elucidate the mechanism of uptake, such as painstaking manipulation of individual effectors with pharmacological inhibitors or specific genetic knockdowns, are limited in scope and biased towards previously studied pathways or the intuition of the investigators. Furthermore, each of these approaches present significant off-target effects, clouding the outcomes. Methods for intracellular transport of nucleic acids are much sought after in the context of both in vitro delivery reagents and in vivo therapeutics. Recently, we found that micellar assemblies of hundreds of amphiphiles consisting of single-stranded DNA which has been covalently linked to a hydrophobic polymer, referred to as DNA-polymer amphiphile nanoparticles or DPANPs, can readily access the cytosol of cells where they modulate mRNA expression of target genomes without transfection or other helper reagents, making them potential therapeutic nucleic acid carriers. However, despite their effective uptake properties and efficacy in the cytosol, it was unknown how these polyanionic structures can enter cells. Indeed, generally, bottlenecks in understanding and achieving delivery and uptake remain a forefront issue in translatability of macromolecular and nanomaterials-based therapeutics generally, including with respect to nucleic acid therapies. The nature of pooled screening requires amplifying a single ~200nt region per cell, leading to screens that require amplification from tens-to hundreds of micrograms of genomic DNA. Inhibitory effects of high DNA concentration per PCR have led to a variety of solutions, ranging from simply pooling hundreds of PCR reactions to utilizing restriction enzyme sites present in the lentiviral backbone constant regions flanking the sgRNA to perform DNA gel electrophoresis and size selection to remove undesired gDNA. However, these approaches can be both expensive and have significant handling challenges when scaled to large screens.

Researchers at the University of California, Davis have developed an approach to improve drug delivery to tumors and metastases in the brain. Their multi-barrier tackling delivery strategy has worked to efficiently impact brain tumor management while also achieving increased survival times in anti-cancer efficacy.

Injectable hydrogels are attracting increasing interest for the therapeutic delivery of cells to tissue. However, these hydrogel formulations can suffer from engraftment efficiencies of less than 5% when delivered to native tissue. These poor engraftment efficiency rates are often attributed to high shear stresses during delivery and inability to provide a stable three-dimensional niche at the delivery site. The inventors have developed a technique for encapsulating cells in the pore space between microscopic hydrogel particles by employing the yield stress fluid properties of packs of microgels. The technology protects the cells from mechanical stress during delivery and facilitates integration to the native tissue. During delivery, the packs of microgels undergo plug flow in which the pressure drop across the length of the pipe is compensated solely by frictional forces at the interface between the pipe wall and microgels. At the delivery site, the pack of microgels behave as an elastic solid across the range of physiological frequencies and provide a stable 3D culture paradigm to support engraftment.Furthermore, the inventors address the challenges associated with cryopreserving, transporting, and delivering this injectable formulation from benchtop-to-bedside with a concept for a perfusable delivery device. The device encapsulates cells in the pore space of the microgels and confines the formulation to a fixed volume where researchers can perfuse liquid freeze/thaw or maintenance media, differentiation factors, and anti-inflammatory agents at virtually any time prior to delivery to the tissue. The porous microgel network facilitates this process and makes the formulation amenable to transport and storage which would otherwise be unattainable in hydrogel formulations.

Researchers at the University of California, Irvine have developed a new vaccine which generates a targeted, specific immune response with fewer complications than currently available vaccines.

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Researchers at UCI have developed a minimally invasive mechanism to help deliver and implant a cardiac assist device inside the body to help patients with heart failure.

Bioorthogonal ligations encompass coupling chemistries that have considerable utility in living systems. Among the numerous bioorthogonal chemistries described to date, cycloaddition reactions between tetrazines and strained dienophiles are widely used in proteome, lipid, and glycan labeling due to their extremely rapid kinetics. In addition, a variety of functional groups can be released after the cycloaddition reaction, and drug delivery triggered by in vivo tetrazine ligation is in human phase I clinical trials. While applications of tetrazine ligations are growing in academia and industry, it has so far not been possible to control this chemistry to achieve the high degrees of spatial and temporal precision necessary for modifying mammalian cells with single-cell resolution.

Researchers at the University of California, Davis have developed a new epigenetic editing system that overcomes packaging limitations of viral delivery systems and can be used for multiplexed epigenetic editing of a genome.

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 UC Berkeley and UCSF have developed a bioelectronic device composed of woven fabric to send impulses directly to the brain. While vast scientific advances have been made in the last century in nearly every realm of biomedical science, neuroscience remains one of the last frontiers. While many scientists have made significant headway in terms of our understanding of the underlying mechanisms of brain functions, this progress has yet to result in a plethora of meaningful therapeutic advances. Because of this, many prominent neurological diseases, such as Alzheimer’s, paraplegia, and multiple sclerosis, have few therapeutic options available and no known curative strategies. One therapeutic strategy for neurologic disorders that is currently being explored is through implantable devices. In this schema, devices are implanted directly into the brain to provide electrical stimulation. However, these devices have significant drawbacks including rigidity, a difficult fabrication process, and limited functionality. Stage of Research The inventors have established a new class of bioelectronic device. This device is composed of woven fabric and will conduct and send electrical signals, provide optical stimulation, as well as support a group of cells. These cells can range from inducible pluripotent stem cells (iPSCs), neural stem cells, or fully differentiated neurons. This method also represents several different weave methods to enable unique applications from the device depending on therapeutic need. This schema also provides for the addition of soluble factors as needed. These factors can include growth factors such as BDNF or VEGF to promote cell growth and survival, as well as anti-inflammatory factors such as IL-1ra. Overall, this device is perfectly positioned to enable brain lesion repair, something that has proved difficult in the past due to the terminally differentiated nature of neurons, which makes them unable to regenerate or divide past a certain point in development.

Researchers at the University of California, Davis have developed the first, digital, droplet infusion system capable of high-precision delivery of very low-volume therapeutics or nutraceuticals.

Researchers at UCI have developed a method of treating inherited retinal diseases, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa, by gene therapy of the RPE65 nonsense mutation. This method uses base editor-mediated genome-editing by viral delivery and lead to improved patient treatment through enhanced editing of single base pairs and reduced off-target genomic editing.

UCI researchers developed a new device that uses electricity to drive ion separation across a membrane. This device can increase the energy efficiency of various applications such as artificial photosynthesis, water desalination, and chemical separations.

UCI researchers developed a percutaneous heart valve delivery system to deliver and implant a prosthetic valve. This system incorporates the means to fracture a previously implanted prosthetic valve in situ without interfering with the transcatheter valve to be implanted.

Prof. Huinan Liu’s lab at the University of California, Riverside has developed a novel tunable hydrogel that achieves tunable crosslinking, reversible phase transition, and may be used as a 3DP scaffold. This new hydrogel utilizes dynamic coordination of its innate carboxylic groups and metal ions. Adding methylacrylate or other functional groups is not required for this technology and the resulting hydrogel is less toxic. Since the functionalization of this hydrogel is not required, it is less process-intensive and results in a more cost-effective hydrogel.  In addition, the UV curing is no longer needed since methylacrylate is no longer utilized to crosslink the hydrogel.   Fig 1: Optical micrographs of top view and cross-section of HyA hydrogels printed using cold-stage method and direct writing method. Hydrogels printed using direct writing method showed better structural integrity and stability.

Researchers at the University of California, Irvine have developed artificial red blood cells consisting of hemoglobin that is tethered to polyethylene glycol (PEG) molecules and formed into microspheres.

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