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216 results about "Transferrin receptor" patented technology

Transferrin receptor (TfR) is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration. It imports iron by internalizing the transferrin-iron complex through receptor-mediated endocytosis. The existence of a receptor for transferrin iron uptake had been recognized over half a century back. Earlier two transferrin receptors in humans, transferrin receptor 1 and transferrin receptor 2 had been characterized and until recently cellular iron uptake was believed to occur chiefly via these two well documented transferrin receptors. Both these receptors are transmembrane glycoproteins. TfR1 is a high affinity ubiquitously expressed receptor while expression of TfR2 is restricted to certain cell types and is unaffected by intracellular iron concentrations. TfR2 binds to transferrin with a 25-30 fold lower affinity than TfR1. Although TfR1 mediated iron uptake is the major pathway for iron acquisition by most cells and especially developing erythrocytes, several studies have indicated that the uptake mechanism varies depending upon the cell type. It is also reported that Tf uptake exists independent of these TfRs although the mechanisms are not well characterized. The multifunctional glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH,EC 1.2.1.12) has been shown to utilize post translational modifications to exhibit higher order moonlighting behavior wherein it switches its function as a holo or apo transferrin receptor leading to either iron delivery or iron export respectively.

Muscle targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and method of use thereof to induce exon skipping of exon 44 of dystrophin in a subject

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.
Owner:DYNE THERAPEUTICS INC

Complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and method of delivering oligonucleotide to a subject

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.
Owner:DYNE THERAPEUTICS INC

Muscle-targeting complexes comprising an anti-transferin receptor antibody linked to an oligonucleotide and method of use thereof to induce exon skipping

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.
Owner:DYNE THERAPEUTICS INC

Complexes comprising an anti-transferrin receptor antibody linked to an oligonicleotide and method of delivering oligonucleotide to a subject

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.
Owner:DYNE THERAPEUTICS INC

Anti-transferrin receptor antibody with customized affinity

Disclosed herein is an anti-transferrin receptor antibody that specifically binds to the human transferrin receptor and the rhesus monkey transferrin receptor, comprising i) a humanized heavy chain variable domain derived from the heavy chain variable domain of SEQ ID NO:01, and ii) a humanized light chain variable domain derived from the light chain variable domain of SEQ ID NO:26, wherein the dissociation rate of the antibody for the human transferrin receptor is equal to or less than (i.e., at most) the dissociation rate of anti-transferrin receptor antibody 128.1 for the rhesus monkey transferrin receptor, wherein the dissociation rate is determined by surface plasmon resonance, and anti-transferrin receptor antibody 128.1 has a heavy chain variable domain of SEQ ID NO:64 and a light chain variable domain of SEQ ID NO:65.
Owner:F HOFFMANN LA ROCHE & CO AG

Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping

Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.
Owner:AVIDITY BIOSCI INC

AAV capsid for CNS-range gene delivery by interaction with transferrin receptors

The present letter invention provides an engineered AAV capsid in which at least one protein on the capsid is modified to include an n-mer motif that promotes transduction of the capsid into the central nervous system (CNS) by interaction with a transferrin receptor. Further embodiments provide a carrier system comprising one or more carriers encoding an AAV capsid and a method of delivering a cargo to a CNS. The methods comprise administering an AAV capsid according to embodiments described herein in vivo or in vitro, and the AVV capsid comprises one or more carrier molecules.
Owner:THE BROAD INST INC

Drug delivery compound, oligonucleotide conjugate and application thereof

The invention relates to a transferrin receptor-targeting drug delivery compound as shown in a formula I, an oligonucleotide conjugate and application of the transferrin receptor-targeting drug delivery compound and the oligonucleotide conjugate. The compounds of the present invention are capable of efficiently delivering oligonucleotides to target organs or target tissues. # imgabs0 #
Owner:SUZHOU XIANXING EXCELLENT BIOTECHNOLOGY CO LTD

Blood-brain barrier crossing antibodies

The present invention relates to antibodies or antibody fragments that bind to human and non-human primate transferrin receptors. The antibodies described herein can be used as agents to deliver pharmaceutical compounds into or through cells during receptor-mediated endocytosis and / or transendocytosis processes. As transferrin receptors are also present in the blood brain barrier endothelial cells, one aspect of the invention provides means and methods to increase delivery of pharmaceutical compounds to the central nervous system.
Owner:VLAAMS INTERUNIVERSITAIR INST VOOR BIOTECHNOLOGIE VZW +1

Preparation method of polymer vesicle capable of crossing blood brain barrier

The invention discloses a preparation method of a polymer vesicle capable of crossing a blood brain barrier, and belongs to the field of high polymer materials and medical engineering. The preparation method of the polymer vesicle capable of crossing the blood brain barrier comprises the following steps: synthesizing an amphiphilic block copolymer by utilizing ring-opening polymerization reaction of polycaprolactone and anhydride in an amino acid ring, then assembling the polymer into the polymer vesicle, and modifying a monoclonal antibody of a transferrin receptor on a polypeptide chain. The polymer vesicle prepared by the invention is simple and convenient in preparation process, short in period, good in stability, good in biocompatibility and good in biodegradability, can be used as an excellent carrier of chemotherapeutic drugs, and can effectively realize drug delivery of targeting brain tumor cells across a blood brain barrier. Compared with a commercial drug delivery carrier, the polymer vesicle has the advantage that the permeability of the drug in a bionic blood brain barrier and the targeted uptake rate of brain tumor cells are remarkably improved.
Owner:JIANGNAN UNIV

siRNA SUPPRESSING EXPRESSION OF TRANSFERRIN RECEPTOR 2

Provided is novel siRNA having an RNA interfering action and / or a gene expression suppressing action on mRNA encoding TfR2, or the like. An oligonucleotide or a pharmaceutically acceptable salt thereof, or the like, has a knockdown action on mRNA of transferrin receptor 2, and consists of an antisense strand region containing a target-matching sequence substantially complementary to a target sequence in mRNA encoding TfR2, and a sense strand region containing a nucleotide sequence substantially complementary to the target-matching sequence of the antisense strand region.
Owner:DAIICHI SANKYO CO LTD

Bipeptide modified bionic nano-vesicle as well as preparation method and application thereof

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.
Owner:AFFILIATED HOSPITAL OF NANTONG UNIV

Polypeptide specifically binding to transferrin receptor and application thereof

The invention is applicable to the technical field of molecular biology, and provides a polypeptide specifically bound with a transferrin receptor, the polypeptide comprises a general formula of H1-H2-E1-E2-H3-H4-E3, and H1, H2, H3 and H4 independently comprise an alpha helical domain; the E1, the E2 and the E3 respectively and independently comprise a beta folding structural domain; when the polypeptide is combined with the hTfR1, transferrin is allowed to be combined to the hTfR1; the polypeptides are capable of binding and delivering oligonucleotides. The invention also provides a recombinant nucleic acid encoding the polypeptide, an expression vector comprising the recombinant nucleic acid, a recombinant host cell comprising the polypeptide, the nucleic acid and / or the expression vector, a conjugate of the polypeptide and oligonucleotide, and a corresponding pharmaceutical composition. The polypeptide disclosed by the invention can be highly specifically combined with hTfR1, so that accurate delivery of oligonucleotide is realized, and a practical basis is provided for treating diseases related to gene mutation.
Owner:CHAINGEN BIOPHARMA LTD

PH-responsive drug self-delivery nano system as well as preparation method and application thereof

The invention relates to the technical field of medical nano-materials, and discloses a pH-responsive drug self-delivery nano-system and a preparation method and application thereof.The preparation method comprises the steps that 1, CMNPs is prepared, specifically, through an amidation reaction, the CMNPs are prepared from methotrexate and cis-aconitic anhydride; step 2, synthesizing DSPE-PEG-T12: synthesizing the DSPE-PEG-T12 by virtue of a nucleophilic addition reaction; step 3, preparing a T12 peptide modified erythrocyte membrane; and step 4, preparing T12-RBCM (at) CMNPs: modifying the T12 peptide of the targeted tumor cell transferrin receptor on an erythrocyte membrane, and coating the CMNPs to construct the nano-acquisition system T12-RBCM (at) CMNPs. According to the nano system T12-RBCM (at) CMNPs obtained by the scheme, the tumor cell uptake efficiency can be remarkably improved, cell apoptosis is induced, and proliferation is inhibited; the long-acting circulation and tumor targeting capability is realized, the tumor growth can be effectively inhibited, and the biological safety is good.
Owner:STOMATOLOGICAL HOSPITAL OF CHONGQING MEDICAL UNIV

Bispecific antibodies and methods of use

The invention relates to bispecific antibodies comprising a first antigen-binding domain that specifically binds to TfR and a second, and optionally a third, antigen-binding domain that specifically binds to PD1. The invention further relates to methods of producing these molecules, to methods of using the same, to pharmaceutical compositions thereof, and their use as medicaments for the treatment of cancer, of acute and chronic infections and of Graft-versus-host disease.
Owner:F HOFFMANN LA ROCHE INC

Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping

Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.
Owner:AVIDITY BIOSCI INC

Transferrin receptor (TFR)-binding variable domains of a heavy chain only antibody (VHH), conjugates and uses thereof

Provided herein are TfR binding VHH polypeptides which bind to human and non-human primate TfR, conjugates thereof, and pharmaceutical compositions comprising these. Provided are also methods of use comprising administering TfR binding VHH polypeptides, conjugates thereof or pharmaceutical compositions thereof to deliver agents, including therapeutic agents, to treat a disease or disorder.
Owner:ELI LILLY & CO

Multispecific antibodies

The present invention relates to a multispecific antibody for transporting a compound across the blood brain barrier (BBB), wherein the antibody binds to at least two target proteins selected from the group consisting of the transferrin receptor (TFRC), CD98 (SLC3A2) and PODXL.
Owner:F HOFFMANN LA ROCHE & CO AG

Anti-transferrin receptor antibodies and uses thereof

The present disclosure provides anti-transferrin receptor antibodies, compositions comprising the same and methods of use for delivery of cargo to brain tissue. This disclosure also provides polynucleotides and vectors encoding the anti-transferrin receptor antibodies and cells comprising the same, methods of making the antibodies, and molecules comprising the antibodies.
Owner:BIOGEN MA INC

AAV capsid modifications that enable improved CNS-wide gene delivery through interactions with the transferrin receptor

PCT designated stage expiredWO2025155923A1Compound screeningPeptide librariesGene deliveryCerebroside
Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. Applicants engineered an AAV capsid, BI-hTFRl, that binds human Transferrin Receptor (TfRl), a protein expressed on the blood-brain barrier (BBB). BI-hTFRl was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40-50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson's disease, BI-hTFRl substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9.
Owner:THE BROAD INST INC

Use of transferrin-receptor large extracellular vesicles as biomarkers of metabolic-dysfunction associated steatohepatitis

Despite the high prevalence and serious clinical implications of metabolic associated steatohepatitis (MASH) in patients with type 2 diabetes (T2D), MASH is usually overlooked in clinical practice, due to the lack of accurate biomarkers. The inventors evaluated the ability of plasma large extracellular vesicles (lEVs) to serve as noninvasive biomarkers for the diagnosis of MASH, in particular in T2D patients. Proteomic analysis identified Transferrinreceptor on lEVs (TFRC-lEVs) as associated with MASH. The inventors thus measured TFRC- lEVs on plasma samples from patients included in the derivation cohort. The proportion of patients with TFRC-lEVs concentration > 61 ng / mL was significantly higher in patients with MASH than in those with steatosis. TFRC-lEVs > 61 ng / mL remained associated with MASH after adjustment on either usual laboratory variables, or on the NASH-Test or on the Fibroscan FAST-score. When combining TFRC-lEVs with available methods the population suspected of having MASH was 32% and 29%, versus 22% and 16% for NASH-test or FAST score alone, without decreasing specificity. In conclusion, TFRC-lEVs, a marker of hepatocyte ballooning, is a promising biomarker for MASH. It could be used for patients' screening to enlarge recruitment of patients with MASH in clinical trials.
Owner:INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +3

Ultrasonic response bionic piezoelectric nano-drug for treating epilepsy as well as preparation method and application of ultrasonic response bionic piezoelectric nano-drug

The invention relates to an ultrasonic response bionic piezoelectric nano-drug for treating epilepsy as well as a preparation method and application of the ultrasonic response bionic piezoelectric nano-drug. The ultrasonic response bionic piezoelectric nano-drug comprises hafnium-based piezoelectric nano-particles UIO-66-NH2 etched by sulfuric acid, an anti-epileptic drug, a microglial cell membrane and transferrin receptor targeting peptide, wherein the anti-epileptic drug is loaded in hafnium-based piezoelectric nanoparticles etched by sulfuric acid to form a drug loading core; the microcolloid cell membrane coats the outer surface of the drug loading core; the transferrin receptor targeting peptide is connected to a microglial cell membrane. The ultrasonic response bionic piezoelectric nano-drug is high in brain entering efficiency, stable in drug release amount and clear in preparation method path, is suitable for targeted delivery of various anti-epileptic drugs and treatment and research of nervous system diseases such as epilepsy, can adopt an intravenous injection administration mode and non-invasive administration, can avoid injury caused by an operation, and has a good application prospect. The electrical stimulation is generated in vivo without implanting and taking out the electrode, so that secondary injury and infection are avoided.
Owner:THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA

Single-chain donanemab antibody-transferrin fusion protein for enhanced efficacy and indications

The efficacy and indication of donanemab do not depend on the Fc region and are subject to transit across cell walls. They can be expanded by using their scFvs conjugated with N-methyl lobe of transferrin protein connected with an environment-sensitive cleavable linker to prevent exocytosis of the scFv yielding high exposure inside body cells such as in the brain, eye, and cancer cells that overexpress transferrin receptors.
Owner:RNA THERAPEUTICS INC