429 results about "Internalization" 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 inhibits expression or activity of DUX4. 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.

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.

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.

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 inhibits expression or activity of DUX4. 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 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.

The present invention relates to magnetic, catalytically active, and radiosensitizing nanoparticles (NanoXcats) and the method for their production. A method is disclosed for the production of functionalized greigite nanoparticles with a narrowband size distribution (10-30 nm) for use in multimodal cancer therapy. NanoXcats are superparamagnetic Fe3S4 nanoparticles whose surfaces are equipped with polar functional groups. The surface structures of NanoXcats are suitable for conjugation with, or for covalent or electrostatic binding of, active substances, which may be cancer drugs, cell growth inhibitors, or NO donors. Due to the EPR effect, NanoXcats are preferentially internalized by tumor cells. The targeted accumulation of NanoXcats in tumor tissue is achieved by an external inhomogeneous magnetic field. NanoXcats exhibit enhanced catalytic activity in tumor cells.The catalytic activity of intracellular NanoXcats can be triggered, controlled, and enhanced by low-dose X-rays. Surface-bound drugs are additionally activated in tumor cells by the catalytic activity of NanoXcats. NanoXcats act as superoxide dismutase, nitric oxide synthase, and Fenton catalyst. They catalyze, for example, reactions of the superoxide anion radical to hydrogen peroxide, of L-arginine to NO, and of hydrogen peroxide to the hydroxyl radical.

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 PEI and targeting peptide modified magnetic nano-carrier and a preparation method and application thereof. The nano-carrier is regular in morphology and uniform in particle size and has good crystallinity and magnetic performance. E5 polypeptide and RGD cyclic peptide on the surface of the nano-carrier are respectively combined with CXCR4 protein and integrin on the surface of a tumor cell, and the nano-carrier and CXCR4 are internalized into lysosome through an integrin-mediated way, so that the target protein CXCR4 is degraded. The PEI in the nano-carrier can load and deliver siRNA into tumor cells to silence the expression of CXCR4 mRNA (messenger Ribonucleic Acid). Through nucleic acid delivery and a protein targeted degradation strategy, the CXCR4 level of tumor cells is jointly reduced, the migration ability of the tumor cells is inhibited, and meanwhile, the anti-tumor effect of M1 type polarization of macrophages is activated.

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.

Disclosed are a recombinant fusion antibody, and an antibody-drug conjugate and use thereof. The recombinant fusion antibody includes an antibody, at least one lysosome-targeting peptide, and at least one linker peptide, wherein the antibody is fused with the lysosome-targeting peptide to form the recombinant fusion antibody via the linker peptide; wherein the lysosome-targeting peptide is at least one selected from the group consisting of a lysosome-sorting signal peptide from a Golgi-localized, γ-adaptin ear-containing, ARF-binding protein (GGA), a lysosome-sorting signal peptide from a mannose 6-phosphate receptor (MPR), a lysosome-sorting signal peptide from a lysosome-associated membrane protein (LAMP), and a variant; wherein the variant is a peptide with one or more amino acids substituted, deleted, and / or added when aligned with the lysosome-sorting signal peptide from a GGA, a MPR or a LAMP. Compared with the original antibody, the internalization and lysosomal trafficking ability of the recombinant fusion antibody are significantly improved.

Provided is a bispecific antibody against EGFR and c-MET. By means of engineering the amino acid sequences of the Fc segments of binding arms, a KIH structure is formed between the EGFR binding arm and C-Met binding arm of the bispecific antibody, thereby assembling a heterodimer. The bispecific antibody is capable of inhibiting the growth and proliferation of EGFR and / or c-Met positive human tumor cells, mediating antibody-dependent cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), and mediating the internalization and degradation of dual target proteins of EGFR and c-MET, and also has a synergistic effect. The bispecific antibody is simple to prepare and stable in structure, and is expected to better meet clinical treatment requirements on the basis of a better tumor cell selectivity.

Provided herein are methods of internalizing anti-DNA antibodies or DNA-binding antibody fragments into a cell. The methods can be used for disease diagnosis and therapeutic treatments.

Conjugation of dendrimer molecules with one or more carbohydrate moieties significantly enhances targeting of tumor-associated macrophages (TAMs) and microglia by increasing brain penetration and cellular internalization, as compared with dendrimers without modification with carbohydrate molecules. Compositions of dendrimers conjugated with carbohydrate moieties, particularly glucose and / or glucosamine, and one or more active agents to prevent, treat, or diagnose a disease or disorder in a subject in need thereof, and methods of use thereof, have been developed. The compositions are particularly suited for treating and / or ameliorating brain and / or CNS tumors. Methods of treating a human subject having or at risk of brain and / or CNS tumors are provided.

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 relates to the technical field of biological genetic engineering, in particular to construction of recombinant lactobacillus plantarum of an African swine fever virus antigen, and the method comprises the following steps: constructing a lactobacillus plantarum shuttle vector containing different ASFV antigen genes; and referring to a genome sequence of a Chinese isolate CADCHN09 of ASFV disclosed in GenBank. The method has the advantages that an inducer is not needed, antigen protein is efficiently expressed, the dendritic cell (DC) binding peptide for enhancing immune cell uptake and processing is subjected to fusion expression, the oral immunization mode is simple, mucosal immunity is stimulated, and ASFV infection is effectively prevented and controlled; probiotics, namely lactobacillus plantarum, which naturally exist in animal intestinal tracts and can be colonized and copied in digestive tracts for a long time are used as a carrier; key epitopes of proteins such as nucleocapsid protein p72, outer envelope protein CD2v, inner envelope protein p54, p22, pE199L and pE248R, which play an important role in adsorption, internalization, endocytosis and membrane fusion of ASFV, are preferably fused with dendritic cell binding peptide and then are displayed on the surface of lactobacillus plantarum.

A drug delivery platform providing flexible fine tune of cell therapy is disclosed herein. Particularly, an engineered fusion protein is coupled with a high affinity ligand carrying at least one payload of drug to be internalized by the transplanted cell to observe or regulate transplanted cell therapy effects.

The present invention relates to an antibody or an antigen-binding fragment thereof binding to CLDN18.2, an antibody-drug conjugate comprising same, and a use of the antibody and the antibody-drug conjugate. An anti-CLDN18.2 monoclonal antibody according to the present invention comprises a fully human antibody sequence, thereby having low in vivo immunogenicity, and exhibits excellent antigen affinity and binding ability specific to a low expression to a high expression level of the CLDN18.2 protein. Thus, the antibody is expected to exhibit high specificity and safety as an antibody-based therapeutic agent such as in the form of a monoclonal antibody and / or an antigen-binding fragment (scFv), an antibody-drug conjugate (ADC), an immune cell engager, a chimeric antigen receptor (CAR), a multispecific antibody, and the like. In addition, the antibody according to the present invention may undergo cellular internalization, enables an anti-CLDN18.2 antibody-drug conjugate comprising said antibodies to be conveniently prepared, and has excellent yield and quality and thus is expected to be highly likely to be developed as a drug. A drug conjugate comprising the anti-CLDN18.2 antibody according to the present invention has excellent in vivo anticancer efficacy and has an expanded therapeutic index (TI) and thus is expected to be usefully employable for the treatment and / or prevention of cancer diseases expressing CLDN18.2 and related diseases.

The invention discloses an AuAgPt ternary alloy nano-framework, a preparation method thereof and application of the AuAgPt ternary alloy nano-framework in anti-tumor preparations, and belongs to the field of biomedical nano-materials. The AuAgPt ternary alloy nano frame is a hollow octahedral nano frame formed by 12 AuAgPt ternary alloy edges, and the nano frame has plasmon photothermal conversion performance, catalase activity and peroxidase-like activity, and can be used for preparing the nano frame. The aptamer has the characteristics that the aptamer can form a covalent bond with glutathione (GSH), the aptamer with the framework surface capable of being modified and specifically bound with tumor cells is used for tumor targeted delivery and the like, the aptamer can be bound in a targeted manner and internalized into the tumor cells, and after near-infrared laser irradiation, the cell temperature can be increased to 42 DEG C, reactive oxygen species (ROS) can be generated, GSH can be consumed, and the tumor targeting effect is achieved. In addition, the content change of small molecule metabolites in cells can be driven through a low-temperature photothermal effect, the metabolic state is disturbed, the redox balance in the cells is destroyed, the tumor cells are induced to generate ferroptosis and apoptosis, and the low-temperature photothermal treatment of tumors is realized.

Provided are a blocking type GIPR antibody, an antigen-binding fragment thereof, an antibody conjugate thereof, and use thereof in preparing a medicament. The GIPR antibody and the antigen-binding fragment thereof have a relatively high affinity for GIPR protein and bind to the GIPR protein expressed on the cell surface, blocking the cell-activating activity of GIP. The GIPR antibody has relatively good cellular internalization activity. Pharmacokinetic research shows that the GIPR antibody and the antigen-binding fragment thereof exhibit relatively good stability in mice, with an AUC0-t up to 15,033.01 hour × μg / mL. The antibody conjugate prepared by adopting the GIPR antibody shows stable and lasting activity in reducing the weight of laboratory animal models and therefore has wide application prospects.

The invention relates to the technical field of biological detection, in particular to a DNA tetrahedral fluorescent probe and application thereof. In the microRNA targeting probe based on DNA plasticity prepared by the invention, different types of miRNAs cause obvious fluorescence difference of DNA tetrahedrons, that is, the DNA tetrahedral structure (TDN) as the probe can be used for detecting targeting nucleotides. The advantages of natural biocompatibility, structural stability, programmability, easiness in internalization, editability and the like of a DNA tetrahedral nanostructure are utilized, extracellular vesicles serve as a delivery platform, an EV-TDN compound can be synthesized, the safety is improved, the target organ / whole body signal ratio effect is improved, the behavior of EV in a mouse is accurately and quantitatively tracked, and the application prospect is wide. The regeneration capacity and the treatment effect are not influenced. The DNA tetrahedral fluorescent probe TDN designed by the invention can be used for detecting targeted nucleotides; the fate and treatment effect of the EV in a lung organ and even a life system can be represented safely, accurately, noninvasively, in real time and quantitatively, and the method is applied to biosensing and disease diagnosis research.