Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Researchers at the University of California, Davis have developed an algorithm for designing and identifying complex structures having custom release profiles for controlled drug delivery.

Researchers at the University of California, Davis have developed a method and composition for modifying genetic sequences using Adenosine deaminases that act on RNA (ADARs).

This technology introduces a novel vaccine delivery system using thermosensitive hydrogels for sustained antigen release, aiming to improve immune response durability and breadth.

Brief description not available

mRNA-based cancer therapies include vaccination via mRNA delivery of tumor neoantigens, delivery of mRNA encoding for immune checkpoint and other protein therapeutics, and induced expression of anticancer surface proteins such as CAR expression in T cells. Success requires transfection of a critical number of immune cells together with appropriate immune-stimulation to effectively drive anti-tumor responses. UC Berkeley researchers have developed an adjuvant-assisted mRNA LNP delivery method that uses mRNA LNP and adjuvant to enhance delivery of nucleic acids to immune cells in vivo and stimulate immune cells. They demonstrated the use of this system to reduce mRNA reporter protein expression in the liver and enhance protein expression in the spleen in mice and also demonstrated this system can be used to genetically engineer T cells by delivering a Cre-recombinase mRNA construct- transfection and editing of approximately 4% of T cells is achieved in vivo. The immune response is superior in our system compared to current, commercial lipid nanoparticle delivery technologies.

Antibodies against poly(ethylene glycol) (PEG) have the potential to cripple the development of lipid nanoparticle (LNP) based therapeutics and new polymers that can stabilize LNPs are greatly needed. Developing alternatives to the PEG-lipid has been challenging partially because of the synthetic challenges associated with making PEG-lipids.  UC Berkeley researcher have created methods for synthesizing PEG replacement polymers based on RAFT block copolymerization and have shown that the block co-polymers synthesized via RAFT polymerization can replace the PEG on LNPs and can generate LNPs that are more efficient at delivering mRNA than PEG-LNPs and are less immunogenic. Block copolymers synthesized via RAFT have great potential for improving the performance of LNPs given their ability to be rapidly synthesized, the commercial availability of numerous methacrylate monomers and the large functional group tolerance of RAFT. 

Researchers at the University of California, Davis have developed a technology to expedite COVID-19 diagnosis and treatment using viral spike protein (S-protein) targeted peptides Zika virus envelop protein.

The invention entails a unique catheter device utilizing electromotive drug administration (EMDA) to enhance drug penetrance into tissues of the ureter, renal pelvis, and calyces. By incorporating a conductive wire and fluid delivery system, the catheter enables targeted drug delivery, potentially revolutionizing the treatment of kidney stones, urothelial carcinoma, infections, and inflammation without systemic side effects.

The invention pertains to a prosthetic valve featuring a saddle-shaped annulus that synchronously transforms between concave and convex configurations, facilitating seamless opening and closure synchronized with cardiac cycles. Comprising leaflets and support elements, the valve mimics natural heart valve function, enabling effective blood flow regulation and offering versatile deployment options for cardiac and vascular applications.

This technology describes a prosthetic heart valve system designed to accommodate the growth of children.

The rippled sheet was proposed by Pauling and Corey as a structural class in 1953. Following approximately a half century of only minimal activity in the field, the experimental foundation began to emerge, with some of the key papers published over the course of the last decade. Researchers at UC Santa Cruz have explored the structure of and have discovered ways to form new beta rippled sheets. 

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.

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 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.

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. Other techniques for mobilizing HSC to the bloodstream involve a 5-day regimen of G-CSF treatment, that has significant side effects of fatigue, nausea, and bone pain. 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.

Brief description not available

Brief description not available