58 results about "Intracellular Protein Transport" patented technology

The present invention relates to the compositions, methods, and applications of a novel approach to selective cellular targeting. The purpose of this invention is to enable the selective delivery and / or selective activation of effector molecules to target cells for diagnostic or therapeutic purposes. The present invention relates to multi-functional prodrugs or targeting vehicles wherein each functionality is capable of enhancing targeting selectivity, affinity, intracellular transport, activation or detoxification. The present invention also relates to ultra-low dose, multiple target, multiple drug chemotherapy and targeted immunotherapy for cancer treatment.

A system and method for transdermally delivering a biologically active agent comprising one or more electrodes having stratum corneum-piercing projections and a circuit that delivers an electrical signal to the electrodes to electroporate a cell membrane. Preferably, the system is configured to generate homogeneous electrical fields and, more preferably, to generate spherically or semispherically symmetrical electric fields. Methods of the invention include applying a first electric signal to facilitate transdermal transport of the agent and applying a second electric signal to facilitate intracellular transport of the agent.

Novel methods for identification of inhibitors or modulators of binding activities mediated by lectin domains of polypeptide GalNAc-transferases are disclosed. Direct binding activity of GalNAc-transferase lectins has been demonstrated for the first time and methods to measure lectin mediated binding of isolated lectins or enzymes with lectin domains are disclosed. The present invention specifically discloses a novel selective inhibitor of polypeptide GalNAc-transferase lectin domains, which provides a major advancement in that this inhibitor and related inhibitors sharing common characteristics of activity bind lectin domains without serving as acceptor substrate for glycosyltransferases involved in synthesis of O-glycans. This inhibitor is represented by the β-anomeric configuration of GalNAc-benzyl, GalNAcβ-benzyl. Methods for inhibiting intracellular transport, cell surface expression, and secretion of mucins and O-glycosylated glycoproteins without affecting O-glycosylation processing are disclosed using the novel selective inhibitor identified.

I have discovered that trace metals such as copper, zinc, iron, and manganese that are necessary for the proper functioning of superoxide dismutase (SOD) and other deactivators of active-oxygen molecules (which cause aging of skin and other skin disorders), can be delivered from the topical compositions. This is achieved by the preparation of copper and other trace metal complexes with phosphorylated nucleosides, such as nucleotides, and phosphorylated monosaccharides, such as phosphorylated glycosides which act as small molecular weight (SMW) transporter molecules. These trace metal complexes of nucleotides and glycosides can be prepared by an in-situ method in water, water-miscible organic solvent, or a mixture of water and water-miscible organic solvent from commonly available ingredients in concentrations that are desirable and can be accurately controlled. I have additionally discovered compositions to achieve the transport of copper from the surface layers of skin into the deeper layers of skin utilizing SMW transporter molecules; and the intra-cellular storage of copper ions in the cell, for example in a bound form with glutathione; and the intra-cellular transport of copper from glutathione to SOD apoprotein by metallochaperones; and the supply of energetic molecules, such as ATP, ADP, or phosphorylated saccharides for SOD metallochaperones to perform their intra-cellular metal transfer function. These cosmetic or pharmaceutical compositions are useful for antiaging and antiviral benefits.

The present invention relates to a delivery system that comprises a conjugate that facilitates the delivery of a compound such as a biologically-active macromolecule, a nucleic acid or a peptide in particular, into a cell. The present invention also relates to said conjugate for delivery of a compound, such as a biologically-active macromolecule, a nucleic acid or a peptide, into a cell. The present invention further relates to a pharmaceutical composition comprising said conjugate and to its use. The present invention also relates to a method of delivering a compound to a cell or an organism, preferably a patient. The conjugates comprise: (a) at least one module that mediates cell targeting and facilitates cellular uptake, (b) at least one module that facilitates transport to the endoplasmic reticulum (ER), (c) at least one module that mediates translocation from the ER to the cytosol, and (d) at least one compound to be delivered wherein the modules (a) to (c) and the compound (d) are linked to each other in any arrangement.

A system and method for transdermally delivering a biologically active agent comprising one or more electrodes having stratum corneum-piercing projections and a circuit that delivers an electrical signal to the electrodes to electroporate a cell membrane. Preferably, the system is configured to generate homogeneous electrical fields and, more preferably, to generate spherically or semispherically symmetrical electric fields. Methods of the invention include applying a first electric signal to facilitate transdermal transport of the agent and applying a second electric signal to facilitate intracellular transport of the agent.

The invention discloses a preparation method and application of a carbon nanomaterial-immunostimulatory sequence compound. The preparation method comprises the steps of (1) modifying a carbon nanomaterial through polylysine to obtain a polylysine-modified carbon nanomaterial; and (2) mixing the polylysine-modified carbon nanomaterial obtained from the step (1) with an immunostimulatory sequence in a water solution, oscillating for 0.5-3 hours at 20-37 DEG C, and centrifuging, collecting and depositing to obtain the carbon nanomaterial-immunostimulatory sequence compound. According to the carbon nanomaterial-immunostimulatory sequence compound, the carbon nanomaterial serves as a carrier for intracellular transport of the immunostimulatory sequence (CpG DNA), so as to remarkably improve the cellular uptake efficiency of the CpG DNA, protect the CpG DNA from being degraded by nuclease and enhance the immunocompetence of an organism for a long time, so the carbon nanomaterial-immunostimulatory sequence compound has a good medical application prospect.

The invention discloses construction and application methods of escherichia coli with a high yield of producing N-acetylglucosamine, and belongs to the technical field of genetic engineering. According to the construction and application methods disclosed by the invention, the decomposition and the intracellular transport pathways of N-acetylglucosamine and the by-products thereof are blocked by modifying and transforming the existing metabolic pathway of escherichia coli, meanwhile, an exogenous glucosamine acetylase gene is introduced, a complete synthesis pathway from glucose to N-acetylglucosamine is formed in a host, the constructed engineering strain is capable of utilizing glucose or glycerol as a substrate for synthesising N-acetylglucosamine through aerobic fermentation culture, so as to realize industrialized production.

Prodrugs made up of biologically-active short-chain fatty acids or derivatives thereof conjugated to neutral or cationic amino acids capable of intracellular transport by ATB0,+ are provided. The short-chain fatty acid or derivative thereof can be attached to the amino acid through a hydroxyl group of the amino acid to form a fatty acid ester of the amino acid, or it can be attached through the amino group of the amino acid to form a fatty-acid amide of the amino acid. Serine butyrate (O-butyryl serine) is a preferred prodrug. These prodrugs are useful for treatment of colon cancer, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lung cancer, cervical cancer, and cancers resulting from metastases from primary colon cancer sites. Methods of delivering biologically-active short-chain fatty acids or derivatives thereof to cells in need of these molecules and methods of treating diseases using the prodrugs of this invention are also provided.

By adding the novel developed modular antigen transporter molecules (MAT molecules) and other instruments related thereto, the immune system of an individual can be effectively modulated in a targeted manner. The MAT molecules contain a translocation module which transports the MAT molecule inside the cell, an active intracellular targeting molecule resulting in intracellular transport of the MAT molecule to the organelles of the cell which are responsible for antigen processing and an antigen module which determines the specificity of the immune response modulated by the MAT molecule. Optionally, other modules such as tag modules or spacer modules can be contained in the MAT molecule. The invention comprises the inventive MAT molecules, antibodies which are produced using said MAT molecules and therapeutic agents and diagnostic reagents which are produced with MAT molecules. The invention also comprises applications containing said MAT molecules, antibodies, therapeutic agents and diagnostic reagents.

The invention provides a [12] aneN3 cationic lipid containing a targeted group and a fluorescent group and a transgenic vector containing the same. The invention also discloses preparation methods of the cationic lipid and the transgenic vector. The cationic lipid provided by the invention contains the targeted group cholic acid and the fluorescent group naphthalimide simultaneously; the transgenic vector formed by the cationic lipid has lower cytotoxicity, has a certain targeting property on hepatoma cells, not only can monitor intracellular transport and release of vector / DNA complexes in a same cell but also has a certain selectivity on the hepatoma cells to promote the development of gene therapy, and also has higher transfection efficiency; the preparation methods of the cationic lipid and the transgenic vector are simple, mature, and easy to control.

The invention discloses a composition for regulating the sub-health status of the crowd suffering from lipodystrophy. The composition mainly has the effects of reducing the expression of the hypothalamic neuropeptide gamma by influencing human leptin, improving the energy metabolism efficiency, increasing the energy consumption and inhibiting fat synthesis. The other components with fat decomposing effects are combined, so that the metabolism of human adipose tissues is promoted, and the intracellular oxidative phosphorylation effect and synthesis of cell endogenous cholesterol are inhibited. The composition can be used for achieving the effects of effectively infiltrating into the human skin, inhibiting the activity of lipase and reducing the synthesis of fat. By combining the traditional Chinese medicine naprapathy, the absorption and intracellular transport of the composition can be further promoted, the metabolism is promoted, the triglyceride in the fat is decomposed, the excretion of steroid and gallic acid is increased, the excretion of cholesterol and other metabolites can be accelerated, a local shaping effect is achieved, and the contents of glycerin and cholesterol in serum are reduced in an assisted mode. The pharmacological action of the cardiovascular system is improved, and the blood circulation is improved.

New antiviral peptides interfering the binding of the virus to DLC8. A high number of pathogenic agents of viral origin use the dynein based intracellular transport machinery at some point of their infective cycle. The present invention consists of a new antiviral therapy consisting in the inhibition of viral infections produced by those virus that use the dynein system by mechanisms of interference mainly by preventing the interaction between the viral protein and the cellular DLC8 protein. The present invention discloses for the first time the blocking of the function of this interaction by peptides whose sequence comprises or consists of the totality or a partial sequence of the viral protein corresponding to the binding domain with DLC8.

Described herein are nanostraw well insert apparatuses (e.g., devices and systems) that include nanotubes extending through and out of a membrane so that a material can pass through the membrane from a fluid reservoir depot and into a cell grown onto the nanotubes when electrical energy (e.g., electroporation energy) is applied. In particular, the device, systems and methods described herein may be adapted for cell growth viability and transfection efficiency (e.g., >70%). These apparatuses may be readily integratable into cell culturing processes for improved transfection efficiency, intracellular transport, and cell viability.

By adding the novel developed modular antigen transporter molecules (MAT molecules) and other instruments related thereto, the immune system of an individual can be effectively modulated in a targetedmanner. The MAT molecules contain a translocation module which transports the MAT molecule inside the cell, an active intracellular targeting molecule resulting in intracellular transport of the MATmolecule to the organelles of the cell which are responsible for antigen processing and an antigen module which determines the specificity of the immune response modulated by the MAT molecule. Optionally, other modules such as tag modules or spacer modules can be contained in the MAT molecule. The invention comprises the inventive MAT molecules, antibodies which are produced using said MAT molecules and therapeutic agents and diagnostic reagents which are produced with MAT molecules. The invention also comprises applications containing said MAT molecules, antibodies, therapeutic agents and diagnostic reagents.

The invention relates to a method for screening hERG potassium ion channel agonist and detecting toxicity. Particularly, the invention firstly relates to a fusion protein, which contains a fragment (which is used as the N end of the fusion protein, is from a position between 1st to 85th amino acid residues of the N end of the nemathelminth ERG family potassium ion channels UNC-103 protein and has the length of 75 to 85 amino acid residues), hERG or a fragment at least containing S1-S6 transmembrane domains and cyclic nucleotide binding domains, and a fragment (which is used as the C end of the fusion protein, is from a position between 590th to 829th of amino acid residues of the C end of the UNC-103 protein and has the length of 220 to 240 amino acid residues). The invention also relates to a polynucleotide sequence coding the fusion protein, a relevant transgenic nemathelminth, a relevant screening method and application. The inventor builds an in-vivo hERG-intracellular-transport-influence-recognizable compound molecule screening method for screening hERG inhibitors or LQTS (long QT syndrome) relevant channel mutant functional correcting agents for the first time; the novel path and method are provided for hERG toxicity detection and LQTS treatment medicine screening.

The invention provides a method for real-time monitoring of cell endocytosis to study anticancer drugs. The method for real-time monitoring of the endocytosis process provided by the present invention comprises the following steps: 1) adding anticancer drugs to make it act on the cells to be tested; 2) connecting epidermal growth factor on the cell membrane of the cells to be tested by a two-step labeling method -Quantum dot probe; 3) Using a fluorescence microscope to observe and photograph under the condition that the light intensity is less than 100 μW, and track the endocytosis process according to the quantum dot label; 4) Quantitatively analyze the photographed data to obtain a relative endocytosis curve. The method provided by the present invention achieves the study of drug effects by quantitatively analyzing the effect of anticancer drugs on endocytosis through real-time observation throughout the whole process, and also considers the influence of cell shape to standardize the endocytic transport data of different cells, completely It can realize horizontal comparison and provide a new quantitative research method for the research, development, screening and therapeutic effect of anticancer drugs.

Prodrugs made up of biologically-active short-chain fatty acids or derivatives thereof conjugated to neutral or cationic amino acids capable of intracellular transport by ATB0,+ are provided. The short-chain fatty acid or derivative thereof can be attached to the amino acid through a hydroxyl group of the amino acid to form a fatty acid ester of the amino acid, or it can be attached through the amino group of the amino acid to form a fatty-acid amide of the amino acid. Serine butyrate (O-butyryl serine) is a preferred prodrug. These prodrugs are useful for treatment of colon cancer, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lung cancer, cervical cancer, and cancers resulting from metastases from primary colon cancer sites. Methods of delivering biologically-active short-chain fatty acids or derivatives thereof to cells in need of these molecules and methods of treating diseases using the prodrugs of this invention are also provided.

The invention provides a plurality of recombinant microorganisms for producing orotic acid and a method thereof. The recombinant microbial strains have one or more or all of the following characteristics: (1) the synthesis of phosphoribosyltransferase or orotic acid nucleoside monophosphate decarboxylase in an orotic acid metabolic pathway is weakened or completely lost; (2) a corresponding enzymeamount is increased through overexpression of five genes of enzymes participating in the orotic acid synthesis route; and (3) the corresponding transport protein is increased by overexpression of a transport protein coding gene for intracellular transport of orotic acid.

The invention discloses construction and application methods of escherichia coli with a high yield of producing N-acetylglucosamine, and belongs to the technical field of genetic engineering. According to the construction and application methods disclosed by the invention, the decomposition and the intracellular transport pathways of N-acetylglucosamine and the by-products thereof are blocked by modifying and transforming the existing metabolic pathway of escherichia coli, meanwhile, an exogenous glucosamine acetylase gene is introduced, a complete synthesis pathway from glucose to N-acetylglucosamine is formed in a host, the constructed engineering strain is capable of utilizing glucose or glycerol as a substrate for synthesising N-acetylglucosamine through aerobic fermentation culture, so as to realize industrialized production.

ACE receptors are affected in severe acute respiratory distress syndrome related coronaviruses. ACE genes are directly related to the morbidity and mortality of those with cystic fibrosis. The thick, sticky mucus in the respiratory, and digestive systems, is seen in the inherited disease cystic fibrosis. Viral induced sticky mucus in the respiratory and digestive systems can also be appreciated as a response to viral pathogens where the cycle of mucus production in vivo induces the recruitment of more mucus production to the extent that cellular damage occurs within the lower respiratory track requiring intubation as a life saving measure. In the most severe cases mechanical intubation fails due to the fact that no control over the recruitment of mucus production was achieved at the onset. SARS pathology shows inflammatory exudation in the alveoli and interstitial tissue, with hyperplasia of fibrous tissue and fibrosis. Inherited cystic fibrosis pathology shows atelectasis, mucoid impaction, acute and chronic inflammation, bronchiectasis, cyst formation, and fibrosis widespread. A virally induced disorder in relations to ACE2 receptors can be treated successfully at the early onset with inherited cystic fibrosis disease mimicking techniques with the efforts of minimizing the activity and utilization of the ACE2 receptor. Cystic fibrosis lung infections, and opportunistic pathogens contribute to chronic airway inflammation that is characterized by neutrophil / macrophage infiltration, cytokine release and ceramide accumulation. In terms of virally induced forms off ACE2 receptor pathologies, as it related to coronavirus such as Covid 19, presumably ceramide precursors which aid in intracellular transport of the virus into the cell via inflammation and remodeling is present in alveolar tissues of the lung in patients with cystic fibrosis while the same pathology occurs in patients with virally induced forms of ACE2 pathology which to often progresses to SARS or ARDS.

The present invention relates to new recombinant humanized immunotoxin hS83-P34, which contains fusion protein comprising the antigen associated molecule of humanized cytotoxic T cell antigen 4 and human porforin channel forming active molecule. The immunotoxin of the present invention has strict targeting, less tendency of damaging health cell, less toxic side effect, no need of internalization and intracellular transport, high acting efficiency, less likelihood of generating corresponding antibody, weak immunogenicity and less tendency of generating drug resistance. It may be used in treating some tumors and autoimmune diseases and suppressing immunologic rejection reaction in organ transplantation.

A composition and method is described for intracellular delivery of fullerene containing peptides. The composition and method involve fullerene-substituted phenylalanine as part of a peptide based delivery system. The presence of a fullerene-substituted amino acid in a peptide is found to alter the intracellular transport properties of the peptide.

The invention provides a cell-penetrating peptide with negative charge and its homologues, having a cell internalization function. Net charge of the cell-penetrating peptide under physiological conditions is a negative value; an amino acid sequence is ELDGDV, LQEDTPP, DPNEKRD, DHMKQHD, NYTWDQW, TTDRHDL, SEQPAHS, DHYHPFS, SDAKNDL, DPYHPFS, SLTNTEH, TVSKGEE, EHYHPFM, TDTTPLQ, GGSAETG, DGPGTAA, SLTAPDY, PLDVNNM, DGTPVGM, LQNLGEF, DSHLSLM, VGSPDGL, DLNLPFA or PLLEGSL. The invention also provides application as an intracellular transport carrier and application of the cell-penetrating peptide withnegative charge as therapeutic drugs in terms of pharmaceutical application and imaging of the intracellular transport carrier.

The invention discloses application of CD82 / TIMP1 in preparation of medicine for inhibiting migration of human pancreatic cancer cells, and belongs to the technical field of biological engineering. CD82 and TIMP1 are directly combined to trigger the intracellular transport and circulation of TIMP1, block cytoskeleton remodeling, reduce lamellipodia / filopodia projecting formation and inhibit cell viability and migration. TIMP1 enhances an Akt signaling pathway by CD82 on a pancreatic cancer cell membrane, blocks cytoskeleton remodeling, reduces lamellipodia / filopodia projecting formation, inhibits cell viability and migration, and has no effect on the growth of cancer cells. The deep explanation on a TIMP1 / CD82 axis as a new signaling pathway for inhibiting tumor metastasis helps us more clearly know and understand the process of cancer metastasis, and helps find a critical juncture of prevention and control of cancer metastasis.

The present invention identifies compounds that disrupt the interaction between anthrax proteins and LRP5 / 6 receptors, resulting in a reduction in anthrax toxicity. The compounds act to disrupt the intracellular transport of toxin complexes into a target cell. The present invention also provides methods for testing the effect of compounds on Wnt activity, through the use of in vitro experiments involving cells that have in at least one gene mutation involved in the Wnt pathway.

The invention relates to the technical field of cell engineering, and in particular relates to establishment and application of a melon transient expression system. A construction method comprises the following steps of: (1) performing enzymolysis on melon tissues by utilizing enzymatic hydrolysate in a dark environment; (2) performing termination treatment on a solution after enzymolysis by using a first termination solution, performing filtering, and centrifuging the filtrate to remove supernatant to obtain a protoplast; (3) performing ice bath on the protoplast, performing centrifuging to remove the supernatant, and performing resuspending by using a resuspension solution to obtain the purified protoplast; (4) continuing to mix with plasmid DNA, adding a PEG4000-Ca<2+> solution, and performing transfecting in a dark environment; (5) adding a second termination solution into a transfection product, and centrifuging a termination product to obtain a protoplast containing the plasmid DNA; and (6) continuing to incubate in a dark environment, and performing centrifuging to remove the supernatant to complete transient expression. The system is stable and can be used for various functional analysis, such as gene expression analysis, subcellular localization, intracellular protein transport analysis and protein interaction.

Described herein are nanostraw well insert apparatuses (e.g., devices and systems) that include nanotubes extending through and out of a membrane so that a material can pass through the membrane froma fluid reservoir depot and into a cell grown onto the nanotubes when electrical energy (e.g., electroporation energy) is applied. In particular, the device, systems and methods described herein may be adapted for cell growth viability and transfection efficiency (e.g., >70%). These apparatuses may be readily integratable into cell culturing processes for improved transfection efficiency, intracellular transport, and cell viability.

The invention discloses a multifunctional nano graphene oxide (NGO) compound for treating osteoarthritis (OA), which is mainly composed of biocompatible functional NGO PEG-BPEI-NGO (PPG) and KGN, NGOis functionally modified by amino-terminated polyethylene glycol (PEG) and branched polyethyleneimine (BPEI), the biocompatible functional NGO product PEG-BPEI-NGO (PPG) is synthesized, non-covalent loading of hydrophobic KGN molecules (PPG-KGN) is carried out through pi-pi accumulation and hydrophobic action, MSCs and PPG-KGN are co-incubated before articular cavity injection, and the intracellular transport efficiency of KGN can be improved through PPG-KGN to obtain KGN enhanced MSCs (BMSCs (PPG-KNG)). The BMSCs (PPG-KNG) has higher chondrogenic differentiation characteristic, can effectively inhibit the development of osteoarthritis, relieve joint gap stenosis and subchondral osteosclerosis, improve osteoarthritis pain and promote tissue regeneration, can better assist stem cell treatment, and provides conditions for relieving osteoarthritis symptoms and improving pathophysiology.