Abstract: Novel direct thrombin inhibitors are provided herein, along with methods for their use as anticoagulants. The direct thrombin inhibitors described herein are useful in treating and/or preventing thromboembolism and bleeding or clotting disorders. Also provided herein are methods for inhibiting thrombin in a cell using the compounds and compositions described herein.

Abstract: Novel soluble epoxide hydrolase (sEH) inhibitors are provided, along with methods for their use. The soluble epoxide hydrolase inhibitors are useful in treating and/or preventing sEH-related related diseases, such as Alzheimer's disease and inflammation. Also provided are methods for inhibiting soluble epoxide hydrolase in a cell using the compounds and compositions described herein.

Abstract: Compositions containing MiniVectors and gene therapy uses, including long term repeated gene therapy uses, to treat liver fibrosis or liver cancer.

Abstract: Provided are specific binding molecules, or fragments thereof, that bind to an epitope of IL13R?2, a receptor polypeptide preferentially found on the surface of cancer cells rather than healthy cells. Exemplary specific binding molecules are bispecific binding molecules that comprise a fragment of an IL13R?2 binding molecule and a peptide providing a second function providing a signaling function of the signaling domain of a T cell signaling protein, a peptide modulator of T cell activation, or an enzymatic component of a labeling system. Also provided are polynucleotides encoding such a specific binding molecule (e.g., bispecific binding molecule), vectors, host cells, pharmaceutical compositions and methods of preventing, treating or ameliorating a symptom associated with a cancer disease such as a solid tumor disease (e.g., glioblastoma multiforme).

Abstract: Embodiments of the present disclosure pertain to compositions that include a compound that inhibits the histone acetyl transferase activity of a protein, such as p300 and/or CBP. Further embodiments of the present disclosure pertain to methods of inhibiting the histone acetyl transferase activity of a protein by exposing the protein to a composition that contains one or more of the compounds of the present disclosure. The compositions of the present disclosure may be exposed to a protein in vitro or in vivo. Additional embodiments of the present disclosure pertain to methods of treating a cancer in a subject by administering a composition of the present disclosure to the subject in order to treat the cancer.

Abstract: Provided are methods of inhibiting spreading depolarization in a subject by administering a sigma-1 agonist or a sigma-1 positive modulator to the subject. In some cases the subject is administered fenfluramine as the sigma-1 positive modulator. In some cases, the subject has been diagnosed with epilepsy, traumatic brain injury, migraines, stroke, ischemic attacks, hypoxia or an increased risk of sudden unexpected death in epilepsy (SUDEP), or a combination thereof.

Abstract: Embodiments of the disclosure concern treatment of cancer utilizing methods and compositions that block CD47 such that tumor associated macrophages (TAMs) are not inhibited by CD47 and are able to phagocytose and kill tumor cells. In specific embodiments, the compositions and their use concern fusions of an entity that binds CD47 and an entity that binds cells having FC receptors, such as the FC receptor on TAMs. Certain embodiments concern gene therapy that produces a fusion of the ectodomain of SIRPa and the constant region of IgG4 at a localized tumor or tumor microenvironment, for example. In specific cases, gene transfer is utilized to deliver SIRPa fusion genes into a tumor and/or tumor microenvironment so that the molecules can be expressed locally to increase efficacy (given that the expression of the molecules will be highest at tumor sites) and decrease potential toxicities.

Abstract: Some embodiments are directed to methods for serially expanding an artificial heart valve within a pediatric patient. For example, the artificial heart valve can be implanted into the pediatric patient during a first procedure, and then expanded during a second procedure to accommodate for the pediatric patient’s growth. Some embodiments include introducing an expander into the implanted valve when the frame is expanded to a first working diameter, and then actuating the expander to expand the frame to a second working diameter greater than the first working diameter, to accommodate for the pediatric patient’s growth.

Abstract: The present disclosure concerns methods and compositions related to cancer treatment comprising targeting of SRC-3 in immune cells, including T cells such as T regulatory cells. The targeting of SRC-3 in T regulatory cells in particular is effective to eradicate tumors in mammals. In specific cases, the T regulatory cells are subjected to CRISPR ex vivo to produce cells suitable for adoptive cell transfer. In some cases, one or more agents that target SRC-3 are also administered to the individual and/or are exposed to the cells prior to administration.

Abstract: The present disclosure concerns methods and compositions related to cancer treatment comprising targeting of SRC-3 in immune cells, including T cells such as T regulatory cells. The targeting of SRC-3 in T regulatory cells in particular is effective to eradicate tumors in mammals. In specific cases, the T regulatory cells are subjected to CRISPR ex vivo to produce cells suitable for adoptive cell transfer. In some cases, one or more agents that target SRC-3 are also administered to the individual and/or are exposed to the cells prior to administration.

Abstract: Embodiments of the invention concern copolymers and nanoparticles for use as delivery agents for one or more agents for therapy for a medical condition of humans and animals. Some of embodiments of the invention provide new reagents for biomedical research in cell culture, animal models and plants, for example. The copolymers comprise PLGA and PEI and, in some embodiments, also comprise 1-(3-aminopropyl)-4-methylpiperazine (APMP), Fc binding peptide and/or antibody. In certain embodiments, APMP-PLGA-PEI, Fc binding peptide/antibody-PLGA-PEI or Fc binding peptide/antibody-APMP-PLGA-PEI nanoparticles comprising one or more therapeutic agents are delivered to an individual in need thereof or used for biomedical research in cell cultures, animal models and plants.

Abstract: Embodiments of the disclosure include compositions and methods for generating RNA nanostructures, particularly in a cell. In particular embodiments, RNA subunits comprising at least one three-way junction and at least one kissing loop are configured such that multiple RNA subunits can polymerize into a specific structure. In particular embodiments, the RNA subunits are configured such that sequence of at least one kissing loop is complementary to sequence of another kissing loop, such as on another RNA subunit, and the summation of multiple RNA subunits having specific individual structures results in a combined polymerized structure of a defined shape. In specific embodiments, an RNA nanostructure generated from methods herein is utilized for an application, such as manufacturing or genetic modifications in a cell.

Abstract: Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.

Abstract: Some embodiments are directed to methods for serially expanding an artificial heart valve within a pediatric patient. For example, the artificial heart valve can be implanted into the pediatric patient during a first procedure, and then expanded during a second procedure to accommodate for the pediatric patient's growth. Some embodiments include introducing an expander into the implanted valve when the frame is expanded to a first working diameter, and then actuating the expander to expand the frame to a second working diameter greater than the first working diameter, to accommodate for the pediatric patient's growth.

Abstract: Embodiments of the disclosure include methods and compositions for treatment of a medical condition related to the liver, including at least viral infections and liver cancer, for example. In specific embodiments, immunotherapies are provided for delivering polynucleotides locally to the liver, wherein the polynucleotides encode particular gene products that include bispecific antibodies, including those that target certain liver antigens, for example.

Abstract: Embodiments of the invention employ methods and compositions for enhancing potency of immune cells that express one or more therapeutic proteins. In certain cases, the methods modulate expression of a CAR transgene in an immune cell, such as a T cell. Specific embodiments employ the exposure of cells and/or individuals to be treated with the cells with an effective amount of at least one agent that upregulates expression of the therapeutic protein, such as a mitogen, histone deacetylase inhibitor, and or DNA methyltransferase inhibitor.

Abstract: Embodiments of the disclosure encompass systems, methods, and compositions related to selective advantages to somatic cells that harbor one or more particular genetic modifications. In particular embodiments, there is selective expansion of gene-targeted cells wherein the strategy involves deletion of an essential gene product that is replaced with targeted integration that also includes integration of a therapeutic transgene. The cells that harbor the replaced essential gene product, and thereby the therapeutic transgene, are selected for using pharmaceutical or nutritional agents that are linked to the function of the essential gene product.

Abstract: The present disclosure provides a 3?UTR CRISPR-dCas13 Engineering System, and methods of using said system, that allows for the manipulation of the length of 3?untranslated regions by using gRNAs to guide catalytically dead Cas13 to sites upstream and/or downstream of the desired poly adenylation sites. One aspect of the disclosure provides a system for modifying the length a 3? untranslated region (UTR) of an mRNA transcript.

Abstract: Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.

Abstract: Provided herein are methods of expanding CD161+ T cells. Also provided are methods and compositions for generating modified CD161+ T cells comprising a chimeric antigen receptor (CAR). In particular aspects, CAR-expressing T cells are produced, expanded, and/or used in disease (e.g, cancer) treatments.