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65 results about "Endosomal membrane" patented technology

In cell biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway originating from the trans Golgi membrane.

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

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

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

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

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

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

Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and / or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis / cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.
Owner:NAT TECH & ENG SOLUTIONS OF SANDIA LLC +1

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

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

Poly(beta malic acid) with pendant leu-leu-leu tripeptide for effective cytoplasmic drug delivery

The invention relates to the use of Polycefin-LLL nanoconjugate as a means of cytoplasmic delivery of drugs. In one embodiment, the present invention provides a drug delivery molecule, comprising a polymerized carboxylic acid molecular scaffold covalently linked to L-leucylleucylleucine. In another embodiment, the Polycefin-LLL includes drug antisense morpholino oligos, targeting antibodies, and a pH-sensitive endosome escape unit. In addition, the drug could be siRNA, microRNA, and aptamer.
Owner:CEDARS SINAI MEDICAL CENT

Methods of Light Activated Release of Ligands from Endosomes

Methods for delivering ligands to a cell by using light to activate fluorescent ligands causing their release from endosomes. The instant methods thus increasing the efficiency of ligands, e.g. in vitro or at localized sites within a subject. The invention provides for the release of ligands by shining a light source on a cell to promote release of ligands into the cell where they can effect their function.
Owner:LIFE TECH CORP

Targeting cell-penetrating peptide vector based on histidine and application

The invention discloses a targeting cell-penetrating peptide vector based on histidine and an application. The amino acid sequence of the targeting cell-penetrating peptide vector based on histidine is REDV-YGRKKRRQRRR-PKKKRKV-Hm, wherein m ranges from 4 to 12. The targeting cell-penetrating peptide vector based on histidine has better biocompatibility, has a cell-penetrating function, a nuclear localization function, an endothelial cell targeting function and a certain pH buffer effect and can more easily escape from an endosome, so that the gene delivery effect is improved, the purposes of promoting cell migration and proliferation and promoting forming of blood vessels are achieved, and the current problems of non-virus vectors are solved.
Owner:TIANJIN UNIV

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

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

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:NAT UNIV OF SINGAPORE

Wild-Type Receptor Assays

A method for determining ligand activation of receptors using cells expressing genetic constructs of a fusion protein of at least a binding domain of an auxiliary protein and a fragment of β-galactosidase, a fusion protein of an endosome-associated protein and a complementary fragment of β-galactosidase, and a wild-type receptor. The receptors are characterized by binding to the auxiliary protein-binding domain upon activation by an agonist and then endocytosing associated with an endosome to which the endosome-associated protein binds. Cells are incubated with a candidate ligand followed by lysis with a lysing medium comprising a substrate for the β-galactosidase. The enzyme product is then detected as a measure of the activation of the receptor.
Owner:DISCOVERYX CORP

siRNA echovirus delivery system with shell-core structure and application of system

The invention discloses a siRNA echovirus delivery system with a shell-core structure. The core of the structure refers to polyarginine-modified or polyhistidine-modified chitosan coated siRNA, and the shell refers to albumin modified by polypeptide containing an RGD group sequence and by arginine. The delivery system can recognize tumor cells in a targeted mode, after the system enters in an endosome-lysosome acid environment, the protein shell is removed, the exposed core can escape from the endosome-lysosome, and under the intracellular GSH reduction condition, siRNA is released. The delivery system is good in stability, high in gene loading capacity and excellent in active target performance, and can significantly improve the gene silencing effect of siRNA and effectively inhibit the growth and metastasis of tumor cells.
Owner:NANTONG UNIVERSITY

Chimeric pcsk9 proteins, cells comprising same, and assays using same

A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin / kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.
Owner:ADAERATA
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