79 results about "Receptor degradation" patented technology

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.

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 promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

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 promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

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.

The invention discloses injection type facial filler composition gel for medical beauty as well as a preparation method and application of the injection type facial filler composition gel, and belongs to the technical field of biomedical materials. The composition gel comprises a combined gel matrix and polycaprolactone microspheres, wherein the combined gel matrix comprises an aqueous solution for injection, sodium carboxymethyl cellulose and human recombinant collagen; according to the composition gel, a combined gel matrix and polycaprolactone microspheres are mixed according to a specific proportion, amino acid residues of human-derived recombinant collagen in the combined gel matrix serve as binding sites of cell surface receptors to improve the cell recognition and attachment capacity of the polycaprolactone microspheres, and the amino acid residues are organically combined with sodium carboxymethyl cellulose to improve the cell recognition and attachment capacity of the polycaprolactone microspheres. The durability and biocompatibility of the shaping effect of the human-derived recombinant collagen at the injection site are improved; the composition prepared by the invention is good in gel fluidity, high in elastic modulus and high in dynamic viscosity, and can meet the expected mechanical and rheological properties of a facial filling agent for cosmetic and plastic surgery.

The present disclosure relates to compositions and methods relating to interferon agonists and their engineered polypeptides. The engineered polypeptides have specificity to receptors in immune systems mediated by Type I interferon (IFN). The present disclosure also relates to methods and system for identifying surrogate agonists for cell surface receptors including dimeric and trimeric receptors.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

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 activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is described. Methods of generating same and using same are also described.

Provided herein is disclosure of a recombinant bifunctional protein or polypeptide capable of binding to a cell surface receptor for lysosome targeting that is made up of an N-glycosylated peptide comprising at least one N-glycan group and a protein of interest, or antibody or antibody fragment capable of binding to a protein of interest. Also provided herein are methods for producing said recombinant bifunctional protein. Also provided herein are methods for lysosomal degradation of a protein of interest comprising introducing to a cell the peptide sequence of the recombinant bifunctional protein.

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 promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention discloses a PROTAC chimera for targeted degradation of an ROR [gamma] t receptor and application of the PROTAC chimera, the structure of the chimera is RW-L-Re, Re is a ligand capable of being combined with E3 ubiquitin ligase, L is a linking group covalently combined with at least one Re and at least one RW, and Rw is a target protein ROR [gamma] t binding ligand and is selected from one of the following structures. A series of PROTAC chimeras capable of degrading an ROR gamma t receptor in a targeted manner are designed and synthesized for the first time, a ternary complex is formed mainly by combining a target protein ligand and an E3 ubiquitin ligase ligand with POI and E3 ligase respectively, and then the POI is labeled with a ubiquitination tag and is further degraded by proteasome. Experimental results prove that the PROTAC chimera designed by the invention has excellent ROR [gamma] t receptor degradation activity, and can be used for preparing related drugs for treating autoimmune diseases or tumors.

The invention relates to the technical field of biomedicine, in particular to an immunoregulation chiral material as well as a preparation method and application thereof, and the immunoregulation chiral material is formed by self-assembly of an immune active component and a delivery carrier. The immunocompetence component is selected from chiral peptide modified distearoyl phosphatidyl ethanolamine-polyethylene glycol, and the chiral peptide is formed by connecting 6-10 D-alanine monomers through amido bonds. The material can realize accurate targeting on target cells by virtue of specific three-dimensional recognition of chiral peptides and immune cell surface receptors, and reduces non-specific action on normal tissues; a delivery carrier represented by lipid nanoparticles can effectively protect chiral peptides from in-vivo enzymolysis and improve the cycling stability of the chiral peptides, and natural carriers such as exosomes can enhance the biocompatibility and tissue penetrability of the material, so that a new strategy is provided for immunotherapy of diseases such as tumors and the like; the compound is expected to be applied to clinical treatment as a novel immunotherapy drug.

The invention discloses an epigenetics method for improving the cryopreservation efficiency of sheep semen. The method comprises the following steps: extracting seminal fluid of Donflilien and Hu sheep hybrid F1-generation sheep, dividing the seminal fluid into a fresh group and a frozen group, carrying out somatic cell removal and small non-coding RNA extraction, screening out differentially expressed microRNAs by utilizing a Pandorah sequencing technology, analyzing a target gene and a signal channel of the microRNAs, and determining the seminal fluid of the Donflilien and Hu sheep hybrid F1-generation sheep. The small non-coding RNA related to sperm cryopreservation is found to mainly relate to key biological processes such as oxidative stress response and cell surface receptor signal channels. The screened differentially expressed small non-coding RNA is added into the frozen semen through methods such as in vitro chemical synthesis, so that the artificial fertilization conception rate of the frozen semen is remarkably increased.

The invention relates to the technical field of cell-loaded biological medicine, in particular to a novel efficient nucleic acid delivery method of a carrier siRNA (small interfering Ribonucleic Acid) medicine, which comprises the following steps: constructing a multifunctional nano-carrier taking a biodegradable polymer as a core, the surface of a multifunctional nano-carrier is modified with a targeting ligand, through specific binding of the targeting ligand and a vascular endothelial cell surface receptor and reversible adjustment of penetration promoting molecules on tight connection, the siRNA / carrier compound can efficiently penetrate vascular endothelium including a blood brain barrier, and meanwhile, the siRNA / carrier compound has the advantages that the targeting ligand can be used for preparing a targeted medicine for treating vascular endothelial cells, and the targeted medicine can be used for treating vascular endothelial cells. According to the present invention, the nucleic acid delivery efficiency is significantly improved, the siRNA can be massively delivered into the tumor or the specific tissue cell due to the precise targeting and the efficient penetrating power, and the selected biodegradable polymer and the selected modification molecule have good biocompatibility so as not to cause the obvious immunoreaction and toxicity in the body.

The invention discloses a low-sensitivity whitening recombinant humanized collagen composition and a preparation method thereof. The low-sensitivity whitening recombinant humanized collagen composition is prepared from modified recombinant humanized collagen, tetrahydrocurcumin, ethyl ascorbic acid ether and dipotassium glycyrrhizinate, the modified recombinant humanized collagen comprises a recombinant humanized collagen chain segment, a polyethylene glycol chain segment modified on the recombinant humanized collagen chain segment, and tetrahydromethyl pyrimidine formyl modified at the other end of the polyethylene glycol chain segment. The modified recombinant humanized collagen can provide proper steric hindrance to achieve the effects of shielding residual antigen epitopes and improving the efficiency of combining target spot cell surface receptors, and cooperates with other mild whitening components to act on various pathways (including oxidation resistance, transport inhibition, enzyme inhibition and inflammation resistance), so that synergistic interaction and irritant hedging are realized, and the skin whitening effect is improved. Therefore, the whitening effect is achieved under low skin irritation.

Provided herein are compositions and methods for treating musculoskeletal fibrosis and / or scarring by gene editing elimination of intracellular signaling through specific cell surface receptors. In some aspects, the compositions and methods relate to TGFB1 ligands. In other aspects, the compositions and methods relate to the TGFB1 receptor (TGFBR1 / TGFBR2). In some aspects, the compositions and methods are useful for treating or preventing post-traumatic fibrosis and / or scarring. In some aspects, the compositions and methods are used to treat or prevent postoperative fibrosis and / or scarring. In some aspects, the compositions and methods are used to treat or prevent local nociceptive feelings, inflammation, degeneration, or morphological changes associated with fibrosis and / or scarring. In some aspects, the compositions and methods are useful for treating fibrosis.

The present disclosure relates to engineered IgG molecules having an IgM Cµ2 domain substituted for all or a portion of an IgG hinge region. Engineered IgG molecules may include one or more targeting moieties that are capable of agonizing a cell surface receptor and may be used, for example, in methods of agonizing certain receptors.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

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 activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The invention discloses a gene editing system for developing a Staphylococcus aureus mastitis resistant Holstein cow aiming at an ADAM10 gene and application of the gene editing system. According to the invention, a novel single-base gene editing ABE technology is used to carry out gene editing on dairy cow fibroblasts, amino acids at main action sites of cell surface receptors ADAM10 of alpha-hemolysin are mutated, and the affinity activity between the two is reduced. Experiments prove that compared with a wild type, the inflammatory sensitivity of the mutated cow mammary epithelial cells to alpha-hemolysin is greatly reduced. Then, gene editing individuals are cultivated through cell nucleus transfer and embryo transfer technologies, and the mastitis resistance of the individuals is achieved.

The present disclosure includes a fusion protein or molecule, called a “Macromolecule that depletes PLA2R-specific antibodies”, including a targeting component that specifically binds to a cell surface receptor or other cell surface molecule, and an antigen component fused directly or indirectly to the targeting component. The antigen component is configured to specifically bind target antigen-specific antibodies. The present disclosure also includes a method of depleting target antigen-specific antibodies from a patient by treating the patient with a macromolecule that targets PLA2R-specific antibodies having an antigen component configured to specifically bind the target antigen-specific antibodies.

The invention belongs to the technical field of biological medicines, and particularly relates to a recombinant collagen repair liquid as well as a preparation method and application thereof. Comprising the following steps: preparing a protein activity enhancer; preparing a recombinant humanized collagen fiber sol; and carrying out photopolymerization to construct the recombinant humanized collagen hydrogel. After turnip pollen polysaccharide is subjected to sulfating modification and compounded with recombinant humanized collagen, the turnip pollen polysaccharide and positively charged collagen amino acid residues can form a stable compound through electrostatic interaction, natural triple helix conformation of the turnip pollen polysaccharide is maintained, collagen aggregation denaturation is reduced, and the activity of the turnip pollen polysaccharide is enhanced; in addition, the recombinant humanized collagen can be assisted in activating cell surface receptors and enhancing adhesion and proliferation of cells, so that the epidermal regeneration promoting capacity of the recombinant humanized collagen is enhanced, and the bioavailability of the recombinant humanized collagen at wounds and the repair treatment effect of the recombinant humanized collagen on the wounded skin can be effectively improved.

Disclosed herein are methods of and compositions for identifying components of a molecular pathway, wherein the molecular pathway comprises a cell surface receptor. The method comprises use of ligand-coated nanoparticles and cells that internalize the ligand-coated nanoparticles. The methods allow analysis of a wide range of ligand- receptor complexes.

The invention provides a growth factor-dextran conjugate as well as a preparation method and application thereof, the growth factor-dextran conjugate consists of a growth factor and dextran, and is obtained by coupling an amino group of the growth factor and a hydroxyl group of the dextran through a chemical reaction; the growth factor-dextran conjugate can protect the growth factor to enhance the stability of the growth factor, reduce the degradation of the growth factor in vivo and prolong the in vivo half-life period of the growth factor; coupled dextran can be combined with a cell surface receptor to promote cellular uptake of growth factors and enhance the effective action concentration of the growth factors in cells, has good biocompatibility and biological safety, and has wide application in research and development of drugs for wound repair and / or treatment of neurodegenerative diseases.

Some 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 a muscle cell. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or an RNAi oligonucleotide.

The present disclosure relates to engineered antigen-binding molecules that include engineered single domain antibody variable domains having substituted cysteine residues. The engineered single domain antibody variable domains may form covalent or non-covalent inter-chain associations. Engineered antigen-binding molecules may include single domain antibody variable domains that target and are capable of agonizing a cell surface receptor and may be used, for example, in methods of agonizing certain receptors.

This invention relates to bifunctional compounds and the use of such bifunctional compounds to reduce plasma levels of extracellular target molecules via lysosomal degradation. These bifunctional compounds have cell surface receptor ligands covalently linked to ligands capable of binding to extracellular target molecules (such as growth factors, cytokines, chemokines, hormones, neurotransmitters, capsids, soluble receptors, extracellular secretory proteins, antibodies, lipoproteins, exosomes, viruses, cell or plasma membrane proteins), wherein said cell surface receptors are associated with receptor-mediated endocytosis, including lysosomal degradation mediated by desialylate glycoprotein receptor (ASGPR) and lysosomal degradation mediated by mannose-6-phosphate receptor (M6PR). Pharmaceutical compositions comprising such bifunctional compounds and methods of treating diseases or disorders mediated by extracellular molecules using such bifunctional compounds are also provided herein.

This invention discloses a recombinant protein pPIC9K-17, its preparation method, and its applications, relating to the field of gene recombination technology. The recombinant protein pPIC9K-17 provided by this invention does not strictly follow the (Gly-X-Y)n triple helix repeat pattern of traditional collagen in its core structural unit. The repeating unit sequence includes a "GAIQ" sequence and a sequence containing collagen characteristics, possessing a certain rigid structural basis and containing receptor-binding or signal activation domains for specific growth factors. The direct tandem connection of multiple such units theoretically enables multivalent binding, enhancing affinity and signal activation efficiency with cell surface receptors, thus surpassing the biological functional limitations of single components (pure collagen or pure growth factors) or simple repeating structures. The recombinant protein of this invention not only effectively promotes the proliferation and migration of skin fibroblasts and accelerates collagen synthesis, but also shows clear efficacy in promoting hair regeneration (hair growth), and can be used to prepare products for skin repair and / or promoting hair regeneration.

There is provided herein a copolymer comprising a ligand moiety that binds to a cell surface receptor, one or two lipophilic polymer blocks and a poly(alpha aminoester) block for the delivery of therapeutic, diagnostic and imaging agents, including small molecules therapeutic agents and nucleic acids, into a cell.