Abstract: The present disclosure is directed to systems, methods, and compositions for functional interaction of fibroblasts with one or more types of immune cells such that the interaction results in modification to the fibroblasts, the one or more types of immune cells, or both. In some embodiments, one or more certain agents are also utilized during the interaction or in lieu of one of the types of cells. In specific embodiments, cells to be used in cellular transplantation therapy are modified to have reduced immunogenicity.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

Abstract: Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and/or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

Abstract: The invention relates to a unique formulation for brain health. The formulation includes a mixture of CBD, THC, THC-V, and/or flavonoids, along with at least one antioxidant, and preferably an emulsifier, spearmint extract and a film-forming agent. The formulation improves memory and cognition as well as prevents and improves symptoms in dementia and related diseases related to deterioration or loss of memory and/or cognition.

Abstract: Described herein are methods of diagnosing systemic sclerosis (SSc) involving the detection of anti-vinculin antibodies. Also described herein are methods of selecting treatment of subjects diagnosed with systemic sclerosis (SSc), and methods of treating systemic sclerosis (SSc).

Abstract: The present invention relates to treatment of subjects having a cancer that is positive for c-Met exon 14 skipping mutations.

Abstract: A method for preparing droplets using a microfluidic chip system is provided. The microfluidic chip system includes a droplet generation device, a power generation device, a collection bottle, a connection device, and a preparation platform, the droplet generation device includes a chip body, the chip body defines a continuous phase inlet for receiving a continuous phase and a dispersed phase inlet for receiving a dispersed phase. The power generation device is activated to form a pressure difference among the collection bottle, the connection device, and the chip body, wherein the pressure difference promotes the dispersed phase and the continuous phase to converge and flow into the collection bottle in form of the droplets.

Abstract: Disclosed herein is an anti-CD79b antibody or antigen-binding fragment thereof, a drug conjugate thereof and use thereof. The anti-CD79b antibody or antigen-binding fragment thereof herein comprises: HCDR1 comprising the amino acid sequence of SEQ ID NO: 1; HCDR2 comprising the amino acid sequence of SEQ ID NO: 2; HCDR3 comprising the amino acid sequence of SEQ ID NO: 3; LCDR1 comprising the amino acid sequence of SEQ ID NO: 4; LCDR2 comprising the amino acid sequence of SEQ ID NO: 5; and LCDR3 comprising the amino acid sequence of SEQ ID NO: 6.

Abstract: Provided herein are compounds and methods for gene silencing. The compound includes a RNA directly conjugated to an albumin-binding group. The method includes administering a compound comprising a RNA directly conjugated to an albumin-binding group to a subject in need thereof.

Abstract: The invention provides a method for inhibiting an intracellular target in a cell with a bispecific antibody comprising contacting the cell with a bispecific antibody having a first Fv fragment with a cell-penetrating determinant and a second Fv fragment with an intracellular target-binding determinant under suitable conditions so that the first Fv fragment causes the bispecific antibody to enter the cell and the second Fv fragment binds the intracellular target in the cell and thereby inhibiting the intracellular target.

Abstract: Production of “regenerative medicine products” is facilitated using a quality by design (QbD) approach. A production device produces a medical product and analyzes a starting material and a central management device determines processing conditions in the production device. By transmitting and receiving data pertaining to the starting material between the production device and central management device data, the medical product is produced while production conditions therefor are continuously optimized. Thus, it is easy to produce a medical product while reducing or eliminating effects from changes in cells and tissues over time, from oscillation during transport, and from changes in surrounding environment such as changes in temperature, and to produce the desired medical product even when there are individual differences in the starting material.

Abstract: A TAT-FXN fusion polypeptide useful in treating subjects diagnosed with Friedrich's Ataxia, hypertrophic cardiomyopathy, or both are disclosed, as are related methods of treatment and pharmaceutical compositions.

Abstract: Novel combination therapies involving nitroxoline, its analogue or pharmaceutically acceptable salt thereof with at least one additional anti-cancer chemotherapy or immunotherapy agent are described. Related kits, pharmaceutical compositions and methods of production are also described.

Abstract: The present invention relates to a composition for repressing the sternness of stem cells, which comprises a material for regulating OCT4 modification. The material for regulating OCT4 modification according to the present invention may regulate the phosphorylation or methylation of OCT4 and inhibit Wnt signaling, thereby effectively reducing the sternness of various stem cells. Therefore, since it can be effectively used in inhibition of proliferation, recurrence and metastasis of cancer, and inhibition of resistance to an anticancer agent, and can reduce sternness even in normal stem cells, it is expected that the time for differentiation of embryonic stem cells into specific cells is shortened, and efficiency is increased.

Abstract: Conformationally-constrained helicases having improved activity and strength are provided. Methods of making conformationally-constrained helicases having improved activity and strength are provided. Methods of using conformationally-constrained helicases having improved activity and strength are provided.

Abstract: Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: A radiosurgical method for treating cardiorenal disease of a patient, the method including directing radiosurgery radiation from outside the patient towards one or more target treatment regions encompassing sympathetic ganglia of the patient so as to inhibit the cardiorenal disease. In an exemplary embodiment, the method further includes acquiring three dimensional planning image data encompassing the first and second renal arteries, planning an ionizing radiation treatment of first and second target regions using the three dimensional planning image data so as to mitigate the hypertension, the first and second target regions encompassing neural tissue of or proximate to the first and second renal arteries, respectively, and remodeling the target regions by directing the planned radiation from outside the body toward the target regions.

Abstract: Methods of using B2 or Alu nucleic acids, or antisense oligonucleotides that modulate the EZH2/B2 or EZH2/Alu interaction and have the capacity to alter cleavage of B2 and Alu RNA, for increasing or decreasing cell and organismal viability.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to P-selectin. The invention also relates to multimeric binding complexes of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold that are binders of P-selectin. The invention also includes drug conjugates comprising said peptides and complexes, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands, complexes and drug conjugates and the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by a cell adhesion molecule, such as P-selectin, including vaso-occlusive crisis and sickle cell disease-related conditions, cancer, or COVID-19.

Abstract: A method for enhancing or restoring adhesion to cells that have partially or completely loss the ability to adhere to a substrate or other cells using nanosized clay crystallites.

Abstract: Disclosed herein are non-myeloablative antibody-toxin conjugates and compositions that target cell surface markers, such as the CD34, CD45 or CD117 receptors, and related methods of their use to effectively conditioning a subject's tissues (e.g., bone marrow tissue) prior to engraftment or transplant. The compositions and methods disclosed herein may be used to condition a subject's tissues in advance of, for example, hematopoietic stem cell transplant and advantageously such compositions and methods do not cause the toxicities that are commonly associated with traditional conditioning methods.

Abstract: The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

Abstract: Interfering nucleic acids and methods of their use in treat prostate cancers, such as aggressive prostate cancers. The nucleic acids may be, for example, short interfering RNA (siRNA), short hairpin RNA (shRNA), antisense RNA, antisense DNA, Chimeric Antisense DNA/RNA, and microRNA (miRNA) oligonucleotides. The oligonucleotide has a seed sequence that is complementary to a sequence of either a gene or an mRNA encoding an androgen receptor (AR) coregulator or a fragment thereof having AR coregulator activity. The nucleic acid compound may have a non-natural modification in the oligonucleotide, and/or an organic moiety conjugated to the oligonucleotide. The oligonucleotide has inhibitory activity against the expression or biological activity of the AR coregulator.

Abstract: The present application relates to the field of cancer, particularly that of cancers with high MDM4 protein levels (such as melanoma, breast, colon or lung cancers, glioblastoma, retinoblastoma, etc.). It is shown herein that direct and selective inhibition of MDM4, e.g., by antisense RNA, leads to growth inhibition of cancer cells and sensitization to chemo or targeted therapies. Also provided are simple ways of determining which patients are most amenable for such treatment by comparing specific transcript levels.

Abstract: Provided are aptamers and aptamer compositions and particularly, although not exclusively, to a bi-specific aptamer capable of binding a tumor cell antigen and an immune cell surface protein.

Abstract: The present invention related to compositions and methods for activating Lck, including in vivo, in vitro and ex vivo uses.

Abstract: A composition containing, as active ingredients, probiotics and a polypeptide with a binding ability to IgE is disclosed. In particular, a synergistic effect of remarkably decreasing food allergy was identified at the time of combined administration of probiotics and a recombinant protein containing an extracellular domain of an alpha subunit of an IgE Fc receptor. Therefore, it is expected that the composition is highly industrially applicable due to being able to exhibit a remarkable therapeutic effect on an IgE-mediated allergic disease as compared with conventional pharmaceutical compositions.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: Methods and compositions using novel Cbl inhibitors for supporting engraftment of immune cells to increase the efficacy of cell-based immunotherapeutics are disclosed. Also provided are cell-based immunotherapy methods and compositions using novel Cbl inhibitors for the propagation of cells desirable for use in cell-based immunotherapies.

Abstract: Disclosed are methods of treating a subject following a small-volume ischemic stroke suffered by the subject and methods of treating a subject with a stroke-induced motor deficit. Disclosed also is a composition for treating small-volume ischemic stroke. In one aspect, the method of treating a subject following a small-volume ischemic stroke comprises administering, to a brain region surrounding a small-volume ischemic core of the subject, a therapeutically effective amount of cells, wherein the cells are descended from mesenchymal stem cells transiently-transfected by a polynucleotide encoding a Notch intracellular domain.

Abstract: The present invention relates to compounds useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various diseases, conditions, or disorders.

Abstract: Disclosed are compounds with immunomodulatory activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysfunctional protein activity.

Abstract: Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells.

Abstract: The invention relates to compositions and methods for enhancing or upregulating utrophin protein production and methods for treating myopathies, such as Duchenne Muscular Dystrophy (DMD). Specifically, the invention relates to compositions, such as oligonucleotides, and methods for enhancing or upregulating utrophin in a subject by blocking binding of let-7c miRNA to the utrophin mRNA 3 untranslated region (UTR).

Abstract: The present invention relates to UNC13A cryptic exon antisense oligonucleotides (ASOs), pharmaceutical compositions containing them, and methods for treating, inhibiting, suppressing, and preventing neurological diseases with them.

Abstract: The present invention provides improved and/or shortened processes and methods for reprogramming TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy. Such reprogrammed TILs find use in therapeutic treatment regimens.

Abstract: Modified cells comprising a transmembrane polypeptide comprising at least one extracellular target receptor-binding domain, a transmembrane domain and an intracellular domain, wherein the intracellular domain is not capable of transducing any signal are provided. Methods of inducing or inhibiting signaling by a target receptor in a target cell comprising contacting the target cell with a modified cell of the invention are also provided.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Abstract: Provided are compositions and methods useful for sensitizing a neuron to insulin or insulin-like growth factor 1 (IGF-1), wherein the neuron is resistant to either insulin or IGF-1. Also provided are compositions and method useful for inhibiting intracellular beta amyloid peptide A?42-mediated decrease in neuronal viability. Also provided are compositions and methods useful for improving synaptic plasticity. Also provided are compositions and methods useful for improving learning and memory. In certain embodiments, the composition comprises (Z)-5-(4-chlorophenyl)-3-phenylpent-2-enoic acid (PS48). In certain embodiments, the method comprises contacting a neuron with PS48. In certain embodiments, the method comprises administering an effective amount of PS48 to a subject in need thereof.

Abstract: A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.

Abstract: The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

Abstract: Novel pyrazolo[1,5-a]pyrido[4,3-e]pyrimidine-2-carboxylic acid compounds, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The pyrazolo[1,5-a]pyrido[4,3-e]pyrimidine-2-carboxylic acid compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: Provided herein are a selective pattern recognition receptor (PRR) agonist and a method of selectively activating a PRR. The selective PRR agonist includes a nucleic acid agonist and a macromolecule conjugated to the nucleic acid agonist. The method includes administering the selective PRR agonist to a subject, and cleaving at least a portion of the macromolecule conjugated to the nucleic acid agonist, the cleaving of at least a portion of the macromolecule permitting the agonist to bind a PRR.

Abstract: The present invention relates to a HLA-A2 subtype-specific PLK1-derived epitope inducing an antigen-specific T cell immune response to a PLK1 protein. More specifically, a HLA-A2 subtype-specific PLK-1-derived epitope inducing an antigen-specific T cell immune response to a PLK1 protein according to the present invention can provide a CD8+ T cell immune response specific for tumor cells.

Abstract: This invention provides purified preparations of an RNA, oligoribonucleotide, or polyribonucleotide comprising a modified nucleoside, and methods of assessing purity of purified preparations of an RNA, oligoribonucleotide, or polyribonucleotide comprising a modified nucleoside.

Abstract: Modular synthetic receptors are provided. The synthetic receptors may include an extracellular domain capable of binding to one or more ligand molecules and may be released from the synthetic receptor after binding, a transmembrane domain derived from the Notch receptor, and an intracellular domain which may have one or more functional activities when released from the synthetic receptor. A method of use for the synthetic receptors is also provided, wherein upon binding of the extracellular domain to a specific ligand, the synthetic receptor undergoes proteolytic cleavage to release either or both the extracellular and intracellular domains. The extracellular binding domain, if released, may continue to bind to its cognate ligand and may carry one or more additional functional activities and the intracellular domain, if released, may stimulate or inhibit one or more intracellular activities.

Abstract: Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Abstract: Disclosed multifunctional compounds, conjugates, macromolecules, and polymers that target dysregulated proteins for degradation. Also disclosed are methods of preparation, compositions, kits, and methods of use relating to the degraders.