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160 results about "Endosome" patented technology

An endosome is a membrane-bound compartment inside a eukaryotic cell. It is an organelle of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane, in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature.

Enhanced transport using membrane disruptive agents

InactiveUS7737108B1Prevent uptakePrevent clearanceBiocidePeptide/protein ingredientsMetaboliteCell layer
Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and / or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and / or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and / or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and / or electrophereis can also be used with the disrupting agents.
Owner:UNIV OF WASHINGTON

Hydrophobic nanotubes and nanoparticles as transporters for the delivery of drugs into cells

Methods and materials for delivering biologically active molecules to cells in vitro or in vivo are provided. The methods and materials use carbon nanotubes or other hydrophobic particles, tubes and wires, functionalized with a linking group that is covalently bound to the nanotubes, or, alternatively, to the biologically active molecule, such as a protein. The biologically active molecule is preferably released from the nanotube when the complex has been taken up in an endosome.
Owner:THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV

Chloroquine coupled antibodies and other proteins with methods for their synthesis

This invention discloses compositions of chloroquine-coupled active agents such as therapeutic antibodies or insulin, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the drug is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a drug directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing the drug for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and antibody or insulin to their site of action.
Owner:KOSAK KENNETH M

pH triggerable polymeric particles

A drug delivery system comprising pH triggerable particles is described. The pH triggerable particles comprise and agent(s) to be delivered, which is encapsulated in a matrix comprising a pH trigger agent and a polymer. Agents including nucleic acids may be delivered intracellularly using the inventive pH triggerable particles. Upon exposure to an acidic environment such as the endosome or phagosome of a cell, the particles dissolve or disrupt due to protonation or an increase in solubility of the pH triggering agent. Pharmaceutical compositions and methods of preparing and administering these particles are also described. These particles may be particularly useful in genetic vaccination.
Owner:MASSACHUSETTS INST OF TECH

Antibodies with modified affinity to fcrn that promote antigen clearance

An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above. The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.
Owner:CHUGAI PHARMA CO LTD

Endosomolytic agents and cell delivery systems

The present invention provides improved cell delivery compositions. In particular, the invention provides biocompatible endosomolytic agents. In a preferred embodiment, the endosomolytic agents are also biodegradable and can be broken down within cells into components that the cells can either reuse of dispose of. In one aspect, the present invention provides endosomolytic agents capable of effecting the lysis of an endosome in response to a change in pH, and methods for effecting the lysis of an endosome. These inventive endosomolytic agents obviate the need for known agents (i.e., chloroquine, fusogenic peptides, inactivated adenoviruses and polyethyleneimine) that can burst endosomes and have negative effects on cells. In another aspect, the present invention provides cell delivery compositions comprising an endosomolytic component that is capable of effecting the lysis of the endosome in response to a change in pH, and an encapsulating, or packaging, component capable of packaging a therapeutic agent to be delivered to cellular or subcellular components.
Owner:MASSACHUSETTS INST OF TECH

Fusion proteins

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.
Owner:HEALTH PROTECTION AGENCY +1

Enhanced transport using membrane disruptive agents

Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and / or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and / or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and / or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and / or electrophereis can also be used with the disrupting agents.
Owner:UNIV OF WASHINGTON +1

Chloroquine combination drugs and methods for their synthesis

This invention discloses compositions of chloroquine-coupled active agents, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the active agent is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to an active agent directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing active agents for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and active agents to their site of action.
Owner:KOSAK KENNETH M

Compositions of nucleic acids and cationic aminoglycosides and methods of using and preparing the same

Compositions that include nucleic acid and cationic aminoglycosides and methods for their use are provided. The subject compositions are characterized by having nucleic acid complexed with a cationic aminoglycoside, where the nucleic acid is condensed. In certain embodiments, the cationic aminoglycoside is a cationic aminoglycoside antibiotic. The composition may further include one or more of: functional groups such as targeting moieties, nuclear localization or targeting peptides, endosomolytic peptides and / or one or more lipids and / or polymers, where the lipids may be provided in a manner to encapsulate the nucleic acid. The present invention also provides methods of using and preparing the nucleic acid-aminoglycoside compositions.
Owner:ARADIGM

Antibodies with modified affinity to fcrn that promote antigen clearance

An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above.The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.
Owner:CHUGAI PHARMA CO LTD

Chloroquine coupled nucleic acids and methods for their synthesis

This invention discloses compositions and methods for preparing chloroquine-coupled nucleic acid compositions. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the nucleic acid needs to be released, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a nucleic acid directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing nucleic acids for therapeutic or other medical uses. The invention also discloses nucleic acid carrier compositions that are coupled to targeting molecules for targeting the delivery of nucleic acids to their site of action.
Owner:KOSAK KENNETH

Fusion proteins

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.
Owner:ALLERGAN INC

Natural or recombinant DNA binding proteins as carriers for gene transfer or gene therapy

A complex for gene transfer a DNA molecule specifically and non-specifically bound to DNA binding protein. Additionally, it can include a chimeric compound for gene transfer. The chimeric compound has a DNA-binding element and a ligand binding element. The chimeric recombinant DNA can also include a binding protein which has a first element for binding to a receptor, a second element for binding to DNA, a third element for destabilizing endosomes and a fourth element for directing the traffic in a protein containing complex in the nucleus of a cell. The complex will be used for the treatment of a variety of diseases.
Owner:BAYLOR COLLEGE OF MEDICINE

Non-cytotoxic protein conjugates

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a galanin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are is also described.
Owner:ALLERGAN INC

Peptide composition and method for delivering substances into the cytosol of cells

Weak-base amphiphilic delivery peptide compositions are described for use in delivering large polar substances (cargo) into the cytosol of animal cells via an indirect endocytosis-mediated delivery process. The delivery peptides, which are predominantly non-ionic at neutral pH, bind but do not permeabilize cell membranes. After endocytosis of both delivery peptides and cargo, acidification of the endosome converts the delivery peptides to their polycationic form, whereupon they permeabilize the endosomal membrane and allow co-endocytosed cargo to pass from the endosome to the cytosol of the cell.
Owner:GENE TOOLS

Block copolymers

Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.
Owner:GENEVANT SCI GMBH

Intracellular nanosensors and methods for their introduction into cells

The invention provides ion-selective sensors capable of selectively measuring ions, e.g., Na+, K+, Cl−, etc., in the cytosol of a single living cell. The sensor comprises one or more quantum dots or a fluorescent dye, a pH-sensitive dye, and optionally an ion-selective component such as an ionophore. These elements may, for example, be disposed in a polymer matrix. The polymer matrix comprises an internalizing moiety which enables the sensor to localize within the cytosol of a cell. The internalizing moiety comprises a small molecule or peptide such as an amine, antepennepedia, mastoparan, or melittin that react under acidic conditions to release a sensor from the confines of a endosome. Once in the cytosol the sensors may detect ionic analytes by selective ion extraction by the polymer, thereby inducing a pH change within the sensor which in turn changes the absorbance of the pH-sensitive dye. The change of absorbance may in turn attenuate the intensity of detectable emissions, e.g., fluorescence, from the quantum dot or dye by directly absorbing its fluorescence emission.
Owner:CHARLES STARK DRAPER LABORATORY

Non-cytotoxic protein conjugates

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.
Owner:ALLERGAN INC

Hydrophobic-group-modified polyethyleneimine derivative and application thereof

The invention belongs to the field of polymer modification, and particularly relates to an acid-sensitive hydrophobic modified polyethyleneimine and application thereof as a gene vector. The derivative contains an acid-sensitive acetal functional group; and specifically, the derivative is an acetal-molecular trimethoxy benzylacetal-trihydroxy ethylacetal (TMB-THME) modified polyethyleneimine derivative, named polyethyleneimine-(trimethoxy benzylacetal-trihydroxy ethane). The polyethyleneimine-(trimethoxy benzylacetal-trihydroxy ethane) provided by the invention enhances the DNA (deoxyribonucleic acid) compounding capability of PEI (polyetherimide) and the interaction with cells, can convert a hydrophobic group into a hydrophilic group in an endosome, and implements the dissociation of theDNA compound and the intracellular release of the DNA; and the cytotoxicity is low.
Owner:SUZHOU UNIV

Intracellular nanosensors and methods for their introduction into cells

The invention provides ion-selective sensors capable of selectively measuring ions, e.g., Na+, K+, Cl−, etc., in the cytosol of a single living cell. The sensor comprises one or more quantum dots or a fluorescent dye, a pH-sensitive dye, and optionally an ion-selective component such as an ionophore. These elements may, for example, be disposed in a polymer matrix. The polymer matrix comprises an internalizing moiety which enables the sensor to localize within the cytosol of a cell. The internalizing moiety comprises a small molecule or peptide such as an amine, antepennepedia, mastoparan, or melittin that react under acidic conditions to release a sensor from the confines of a endosome. Once in the cytosol the sensors may detect ionic analytes by selective ion extraction by the polymer, thereby inducing a pH change within the sensor which in turn changes the absorbance of the pH-sensitive dye. The change of absorbance may in turn attenuate the intensity of detectable emissions, e.g., fluorescence, from the quantum dot or dye by directly absorbing its fluorescence emission.
Owner:CHARLES STARK DRAPER LABORATORY

Receptor-mediated gene transfer system for targeting tumor gene therapy

The invention relates to a gene transfer system binding to a growth factor receptor, comprising 4-element complex gene transfer system consisting of ligand oligopeptide / polycationic polypeptide / endosome release oligopeptide / exogenous DNA or 3-element complex consisting of ligand oligopeptide / polycationic polypeptide / exogenous DNA. The invention exemplifies E5, GE7, GV1 and GV2 systems and they can be targeted for the introduction of exogenous genes into malignant tumor cells or tumor vascular endotheliocytes. They are also able to highly inhibit the growth of tumor cells in animals while p15, p16 or p21WAF-1 was used as exogenous genes. The system according to the invention is a new introduction system in tumor gene therapy.
Owner:SHANGHAI INST OF ONCOLOGY

Fusion proteins

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.
Owner:ALLERGAN INC

Charge reversal Pulullan derivative and synthesis method and application thereof

InactiveCN105566511AConducive to reversing drug resistanceSignificant liver/liver cancer targetingPowder deliveryDigestive systemAmino estersSynthesis methods
The invention relates to a charge reversal Pulullan derivative and a synthesis method and application thereof. The Pulullan derivative is composed of a Pulullan framework, a multi-amino modified group and a beta-carboxylic acid amide modified group, has remarkable liver / liver cancer targeting property, and can quickly respond to a faintly acid tumor microenvironment and a cell endosome / lysosome so as to achieve reversal from electronegativity to electropositivity. By modifying poly(beta-amino ester) (PBAE) / polylactic acid-polyglycolic acid copolymer (PLGA) composite nanoparticles with the Pulullan derivative, liver cancer targeted delivery of nanoparticles can be mediated efficiently, effective release of a carried drug at the tumor position is achieved, and the charge reversal Pulullan derivative is a liver / liver cancer targeted carrier material with excellent performance for drugs, genes and image contract agents and has broad application space.
Owner:TIANJIN MEDICAL UNIV

Method for analyzing single cell inclusion based on micro flow-controlled chip

The invention is a micro-flow control chip-based single-cell endosome analysis, made on a chip platform. First, exert voltage on cell pool and earth cell waste liquor one, the electric power drives the cells to flow from the cell pool to the cell waste liquor one, observe by microscope, and when the cells reach the exit of the detecting channel, make the electrodes of the two pools suspend; at the same time, exert high voltage on run buffer liquor pool and cell cracking liquor pool, and earth waste liquor pool; in this voltage mode, ensure the cells, the cell cracking liquor, screening agent, and run buffer liquor to enter separating channel in order to complete cracking and separating single cell; and detect the endosome on two ends of the channel. It can make single or parallel analysis on the endosome.
Owner:DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI

Tlr agonists

The present invention provides TLR agonist conjugates (compounds) and compositions, as well as methods of using them. The compounds of the invention are broad-spectrum, long-lasting, and non-toxic combination of synthetic immunostimulatory agents, which are useful for activating the immune system of a mammal, preferably a human and can help direct the pharmacophore to the receptor within the endosomes of target cells and enhance the signal transduction induced by the pharmacophore.
Owner:RGT UNIV OF CALIFORNIA

Recombinant nucleic acid useful for inducing protective immune response against allergens

The invention provides a recombinant nucleic acid useful for inducing a protective immune response against an allergen. The recombinant nucleic acid encodes an allergen and a signal peptide that mediates the translocation of the allergen to endoplasmic reticulum and preferably also encodes a second signal peptide that targets the gene to an endosome or a lysosome. The recombinant nucleic acid, when administered to a subject induces a Th 1 type immunity and inhibits IgE production and therefore may be used to prevent and treat an allergic reaction. In various aspects therefore, the invention provides a vaccine and immunogenic composition comprising the recombinant nucleic acid.
Owner:CHUA KAW +1
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