Abstract: The present invention relates to 5?-cap compounds, in particular the stabilization of RNA by such 5?-cap compounds, and provides compositions, such as pharmaceutical compositions, and cells comprising an RNA which is modified with such a 5?-cap compound, as well as methods for producing a peptide or protein of interest using the compositions or cells according to the present invention. Furthermore, the present invention provides the RNA, compositions, or cells for use in therapy, in particular for use in a method of treating a disease or disorder by protein replacement therapy, genome engineering, genetic reprogramming, and immunotherapy; a method for increasing the stability of RNA in cells; a method for increasing the expression of RNA in cells; and a method for providing an RNA with a 5?-cap structure.

Abstract: Disclosed herein is a method of generating exosomes (extracellular nanovesicles) and/or neo-islets from mesenchymal or adipose stem cells or islets, or other cells in a Hollow-Fiber-based Cell Expansion (HFCE) System. Such exosomes and/or neo-islets may be used for the treatment of T1DM, T2DM, or associated microvascular disease.

Abstract: The present disclosure provides a siRNA for inhibiting the expression of apolipoprotein C3 (ApoC3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

Abstract: Provided herein are methods and reagents for treating cancer. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of a DKK1 peptide-loaded MHC antibody provided herein. The methods can further include administering an effective amount of chemotherapy or immunotherapy to said patient.

Abstract: The presents invention relates to a composition for manipulating an immune cell which is used for artificially manipulating an immune cell. More particularly, the present invention relates to a composition for manipulating an immune cell which is used for artificially manipulating an immune cell and a manipulated immune cell comprising an artificially modified immunity regulating gene and an artificial receptor which is produced using the composition, and use thereof.

Abstract: The invention relates to novel bispecific antigen binding molecules, comprising (a) at least one antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP) comprising FAP clone 212 or variants thereof, and (b) at least one antigen binding domain capable of specific binding to CD40, and to methods of producing these molecules and to methods of using the same.

Abstract: The present disclosure provides CasY proteins, nucleic acids encoding the CasY proteins, and modified host cells comprising the CasY proteins and/or nucleic acids encoding same. CasY proteins are useful in a variety of applications, which are provided. The present disclosure provides CasY guide RNAs that bind to and provide sequence specificity to the CasY proteins, nucleic acids encoding the CasY guide RNAs, and modified host cells comprising the CasY guide RNAs and/or nucleic acids encoding same. CasY guide RNAs are useful in a variety of applications, which are provided. The present disclosure provides methods of identifying a CRISPR RNA-guided endonuclease.

Abstract: Embodiments of the invention include systems and media for mammalian cell culture that enhance cell viability which enables biological assays and quantitative studies in tissues such as skin explants. Certain embodiments may be used in coordination with each other or may be practiced separately. An exemplary embodiment of the invention is a culture medium that includes Dulbecco's Modified Eagle's Medium, X-VIVO medium, and subcutaneous adipocyte medium. In one embodiment the culture medium includes approximately 30-60% Dulbecco's Modified Eagle's Medium by volume, approximately 30-60% X-VIVO medium by volume, and approximately 2.5-15% subcutaneous adipocyte medium by volume. Certain embodiments of the culture medium can also include recombinant human stem cell factor. Embodiments of the invention disclosed here are not limited to the brands described and encompass equivalents, as well as combinations, of the individual chemical components that make up the media described herein.

Abstract: Provided are an expression inhibitor of a cancer promoting factor based on the discovery of a new factor influencing the expression amount/level of a cancer promoting factor, and a development tool therefor. Provided are also a diagnostic agent and a diagnosis method for cancer. More specifically provided are: an expression inhibitor of a cancer promoting factor containing at least one kind of inhibitor selected from the group consisting of RBMS expression inhibitor and RBMS function inhibitor; a screening method using as an indicator the expression or the function of RBMS; an expression cassette useful for the method; as well as a diagnostic agent containing a product detection agent for RBMS gene expression and cancer detection method using as an indicator RBMS gene expression amount/level.

Abstract: The invention provides certain specific lipid nanoparticles comprising: (a) one or more nucleic acid molecules; (b) cholesterol; (c) DSPC; (d) PEG-C-DMA; and (e) a cationic lipid; and pharmaceutical compositions comprising the lipid nanoparticles. The lipid nanoparticles and pharmaceutical compositions are particularly useful for delivering a nucleic acid such as siRNA or mRNA to a patient (e.g. a human) or to a cell.

Abstract: Disclosed herein are cyclosporine compounds and methods for use in the treatment or prevention of neutrophil-mediated inflammation, wherein the compounds inhibit the activity of MRP2 and FPR1.

Abstract: Provided herein are compositions and methods for the cryopreservation of immune cells, such as peripheral blood mononuclear cells (PBMCs) by pre-treating the cells with a PTD-MYC fusion protein (e.g., an HIV TAT-MYC fusion protein) prior to freezing. Kits for practicing the methods are also provided herein.

Abstract: Provided are defined culture media for culturing pluripotent stem cells in a suspension culture devoid of substrate adherence, the defined culture media comprising an effective amount of a protease inhibitor; a GSK3? inhibitor and at least one agent selected from the group consisting of a protease inhibitor and a WNT3A polypeptide; a WNT3A polypeptide and a stabilizing agent thereof with the proviso that said stabilizing agent is not a lipid vesicle; and/or a GSK3? inhibitor, with the proviso that the medium is devoid of an ERK1/2 inhibitor. Also provided are cell cultures and methods of suing same.

Abstract: The present disclosure provides methods of treating non-alcoholic steatohepatitis (NASH) in a subject by administering to the subject an inhibitor of IL-27 or IL-27R.

Abstract: The present invention relates to a method of necrosing, causing membranolysis, or causing poration of selective cancer cells. In some aspects, the method includes administering a peptide including PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG (SEQ ID NO:48) or ETFSDLWKLLKKWKMRRNQFWVKVQRG (SEQ ID NO:49) to a selective cancer cell to cause necrosis, membranolysis, or poration of said selective cancer cell.

Abstract: The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

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: 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 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: 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 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: 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 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: 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 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: 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 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: 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: 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 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: 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: 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: 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 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.