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Injectable Extracellular Matrix For Treating Skeletal Muscle Atrophy And Degeneration

The primary therapeutic goal in female pelvic medicine is to restore normal pelvic floor function. Despite this, the current standard treatments are 5 compensatory, as they do not directly target sphincteric and supportive muscle dysfunction and do not reverse the existing injury or halt functional deterioration. Surgical treatments, such as muscle transplantation and transposition techniques, have had some success; however, there still exists a need for alternative therapies. Tissue engineering approaches offer potential new solutions; however, current options offer incomplete regeneration. Many naturally derived as well as synthetic materials have been explored as scaffolds for skeletal tissue engineering, but none offer a complex mimic of the native skeletal extracellular matrix, which possesses important cues for cell survival, differentiation, and migration. The extracellular matrix consists of a complex tissue-specific network of proteins and polysaccharides, which help regulate cell growth, survival and differentiation.Despite the complex nature of native ECM, in vitro cell studies traditionally assess cell behavior on single ECM component coatings, thus posing limitations on translating findings from in vitro cell studies to the in vivo setting. Overcoming this limitation is important for cell-mediated therapies, which rely on cultured and expanded cells retaining native cell behavior over time.Skeletal muscles are composed of bundles of highly oriented and dense muscle fibers, each a multinucleated cell derived from myoblasts. The muscle fibers in native skeletal muscle are closely packed together in an extracellular three dimensional matrix to form an organized tissue with high cell density and cellular orientation to generate longitudinal contraction. Skeletal muscle can become dysfunctional due to a variety of different factors including trauma, atrophy or degeneration.The reconstruction of skeletal muscle, which is lost by injury, tumor resection, or various myopathies, is limited by the lack of functional substitutes.  

Implantable Substance Delivery Devices

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.

XNA enzymes to Validate and Treat Genetic Diseases

Allelic proteins are often considered undruggable targets, because therapeutics that interfere with these proteins while leaving the wild-type protein unharmed are difficult to come by. Researchers at UCI have developed a xeno-nucleic enzyme (XNAzyme) that offers a solution to this problem by selectively cleaving the mRNA of mutant alleles while leaving the wild-type mRNA unharmed. This novel gene silencing technology offers an efficient, safe, and effective approach to treating genetic diseases.

Oxime Crosslinked Hydrogels To Prevent Postsurgical Cardiac Adhesions

Although a wide variety of hydrogels have been developed for a multitude of uses, various functional characteristics have been hard to capture in a controllable manner. A significant feature is the ability to ‘tune’ the gel so its gelling time can be controlled in a manner suitable to its application. In this disclosure, because the gel is both tunable and its composition allows it to bond to tissue, the inventors believe it can be used to address an unmet medical need – the formation of adhesions after cardiac surgery. Current methods used are either drug therapy or various physical barriers but their success is limited.

Selective Antimicrobial Peptides From Human Milk For Treatment Of Severe Infections

Researchers at the University of California, Davis have developed human milk-derived peptides that have demonstrated broad-spectrum, antibacterial, activity against a variety of harmful pathogens - without these peptides harming most, non-pathogenic, bacterial, flora.

Compositions And Methods For Allelic Gene Drive Systems And Lethal Mosaicism

Efficient super-Mendelian inheritance of transgenic insertional elements has been demonstrated in flies, mosquitoes, yeast, and mice. While numerous potentially impactful applications of such so-called gene-drive systems have been proposed they are currently limited to copying relatively large DNA cargo sequences (~1-10 Kb). Many desired genetic traits (e.g., drought tolerance in plants, crop yield, pest-resistance, or insecticide sensitivity), however, result from allelic variants altering only one or a few base pairs. An efficient system for super-Mendelian inheritance of such subtle genetic variants would accelerate a wide array of efforts to disseminate favorable traits throughout populations, or to assemble complex genotypes consisting of point-mutant alleles in combination with insertional transgenes for a multitude of research and applied purposes.

Biosynthetic Production Of L-4-Chlorokynurenine

The non‐proteinogenic amino acid l‐4‐chlorokynurenine (l‐4‐Cl‐Kyn) is a next‐generation, fast‐acting oral prodrug for the treatment of major depressive disorder. Additional studies report that this drug candidate is effective in animal models for the treatment of neuropathic pain, epilepsy, and Huntington's disease.  After active transport across the blood–brain barrier, it is enzymatically converted into the active agent 7‐chlorokynurenic acid, which is a highly selective competitive antagonist of the N‐methyl‐d‐aspartic acid (NMDA) receptor.   Suicide is 2-7x higher in Veterans than non-veterans, and may be related to brain kynurenine pathway (KP) dysregulation and NMDA receptor (NMDAR) hyperactivation.  L-4-Chlorokynurenine (L-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder (Double-Blind, Placebo-Controlled, Phase 2 Trial to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) as Adjunct to Current Antidepressant Therapy in Patients With Major Depressive Disorder (the ELEVATE Study)).

Photocurable Poly(ethylene glycol) as a Bioink for the Inkjet 3D Pharming of Hydrophobic Drugs

UCLA researchers in the Department of Bioengineering have developed a novel inkjet 3D pharming technique that is fast, customizable, and compatible with hydrophobic drugs.

Antimicrobial and Osteoinductive Hydrogel for Dental Applications

UCLA researchers in the Department of Chemical & Biomolecular Engineering developed osteoinductive and antimicrobial hydrogel adhesives for dental applications.

Design Random Heteropolymer To Transport Proton Selectively And Rapidly

Despite decades of effort, it remains challenging, if not impossible, to achieve similar transport performance similar to natural channels. Inspired by the known crystal structures of transmembrane channel proteins, protein sequence-structure-transport relationships have been applied to guide material design. However, producing both molecularly defined channel sizes and channel lumen surfaces that are chemically diverse and spatially heterogeneous have been out of reach. We show that a 4-monomer-based random heteropolymer (RHP) exhibits selective proton transport at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in the RHP leads to well-modulated segmental heterogeneity in hydrophobicity, which facilitates the single RHP chains to insert into lipid bilayers. This in turn produces rapid and selective proton transport, despite the sequence variability among RHP chains. We have demonstrated the importance of:the adaptability enabled by the statistical similaritythe modularity afforded by monomer chemical diversity to achieve uniform behavior in heterogeneous systems. 

Liquid Metal Enabled Multi-Functional Neural Probes with Ultra-Large Tunable Stiffness

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a novel multi-functional neural probe with ultra-large tunable stiffness for electrochemical sensing and chemical delivery in the brain.

Single Conjugative Vector for Genome Editing by RNA-guided Transposition

The inventors have constructed conjugative plasmids for intra- and inter-species delivery and expression of RNA-guided CRISPR-Cas transposases for organism- and site-specific genome editing by targeted transposon insertion. This invention enables integration of large, customizable DNA segments (encoded within a transposon) into prokaryotic genomes at specific locations and with low rates of off-target integration.

New Bright Green Fluorescent Proteins

Fluorescent proteins (FP) have been widely used as research tools in both academia and pharma for many years.  Naturally occurring FP have been mutated to either be brighter, be monomers, and/or for easier folding and expression in cells.  The most common FP to date has been the green fluorescent protein (GFP) of the jelly fish Aequorea victoria which can be expressed in cells and fused with proteins of interest, and has proven to be an excellent tool to study protein localization, expression, signaling, etc. in real time via microscopy and other techniques. 

Temporal Control over DNA-Patterned Signaling Ligands In Vitro Using Sequence-Targeting Nucleases

UC Berkeley researchers have created a new technique that can rapidly “print” two-dimensional arrays of cells and proteins that mimic a wide variety of cellular environments in the body, be it the brain tissue surrounding a neural stem cell, the lining of the intestine or liver or the cellular configuration inside a tumor.  In the new technique, each cell or protein is tethered to a substrate with a short string of DNA. While similar methods have been developed that attach tethered cells or proteins one by one.  By repeating the process, up to 10 different kinds of cells or proteins can be tethered to the surface in an arbitrary pattern. This technique could help scientists develop a better understanding of the complex cell-to-cell messaging that dictates a cell’s final fate, from neural stem cell differentiating into a brain cell to a tumor cell with the potential to metastasize to an embryonic stem cell becoming an organ cell.

Biomimetic Conductive Hydrogels

UCLA researchers in the Department of Bioengineering have developed a novel electrically conductive scaffold system with a hyaluronic acid (HA)-based hydrogel for biomimetic research to treat spinal cord and other central nervous system (CNS) injuries.

Improved Highly Potent Specific Human Kunitz Inhibitor of Fibrinolytic Enzyme Plasmin

UCLA researchers in the School of Medicine have developed mutant polypeptides of the tissue factor pathway inhibitor-2 (TFPI-2) Kunitz domain 1 (KD1), which can serve as potent inhibitors of fibrinolysis.

Gelatin Methacryloyl Based Microneedle

UCLA researchers in the Department of Bioengineering have developed gelatin methacryloyl microneedles (GelMA MN) for minimally invasive, sustained transdermal drug delivery.

TRM:Sox9CreER BAC Transgenic Mice

These transgenic mice express an inducible version of cre recombinase mice under the direction of a Sox9 promoter. They are suitable for performing cre-recombination in pancreatic ductal cells and their progenitors.

Use Of Non-Ionic Copolypeptide Hydrogels For Cell Suspension And Cell And Molecule Delivery

UCLA researchers in the Departments of Bioengineering, Chemistry and Biochemistry, and Neurobiology have developed novel copolypeptide hydrogel formulations for the delivery of cells and molecules to locations throughout the body, including the central nervous system.

Hydrodealkenylative C(Sp3)–C(Sp2) Bond Scission

UCLA researchers in the Department of Chemistry and Biochemistry have developed a new chemical reaction that combines ozone, an iron salt, and a hydrogen atom donor to enable hydrodealkenylative cleavage of C(sp3)–C(sp2) bonds in a widely applicable manner.

Hv1 Modulators and Uses

Researchers at UCI have engineered a class of Hv1 polypeptide modulators that selectively modulate Hv1 voltage gated channels while leaving other voltage gated channels unaffected. With no Hv1 modulators currently on the market, this class of Hv1 polypeptide modulators could provide solutions in birth control, autoimmune therapies, and tumor reduction.

Novel Non-Antibody-Based Chimeric Antigen Receptor Against HIV That Also Protects Cells From Infection

UCLA researchers in the Department of Medicine have developed a novel chimeric antigen receptor (CAR) that targets T cells against HIV while protecting T cells from HIV infection.

Novel Protease for Oncology and Inflammatory Diseases

The technology is a novel protease that reduces the ability of cells to respond to the inflammatory cytokine Tumor Necrosis Factor (TNF). High TNF levels have been linked to rheumatoid arthritis, Crohn’s disease and many types of cancers.

Treatment Of Lysosomal Storage Disorders

UCLA researchers in the Departments of Neurology have developed a novel treatment for Lysosomal-storage diseases (LSDs) with neurological impairment.

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