19 results about "Apolipoprotein e4" patented technology

A gene therapy vector comprising an expression cassette coding for a mammalian apolipoprotein E that has a residue other than arginine at at least one of positions 112, 136, or 158, but is not a mammalian apolipoprotein E that has R112, R136 and R158 or a mammalian apolipoprotein E that has C112, R136 and C158, or coding for an antibody that binds to APOE4 or disrupts the binding of APOE to heparan sulfate proteoglycans, and methods of using the vector, are provided.

The invention provides a lipid nanoparticle and application thereof, and particularly provides a cholesterol-free LNP delivery system based on sterol ionizable lipid. According to the system, a sterol group is integrated into an ionizable lipid skeleton as a hydrophobic tail through molecular design to form a novel sterol ionizable lipid, and the novel sterol ionizable lipid is self-assembled with an auxiliary lipid and a PEG-lipid to form a stable three-component LNP. The problem of high liver enrichment caused by the fact that traditional four-component LNP depends on cholesterol is solved, the affinity of core lipid and apolipoprotein E is remarkably reduced, and an ApoE / LDLR-mediated liver cell uptake way is effectively avoided. Under the condition that cholesterol is completely not needed, the LNP achieves high encapsulation efficiency and excellent stability on mRNA at the same time, liver enrichment is greatly reduced, the targeting performance on extrahepatic tissues such as the spleen is improved, high transfection efficiency and good biocompatibility are achieved, and an innovative platform is provided for delivery of extrahepatic disease RNA drugs.

The invention belongs to the technical field of disease detection and health examination, and particularly relates to an enzyme-linked immunosorbent assay method of apolipoprotein E and application of the apolipoprotein E in glaucoma diagnosis. A capture antibody used by the kit is 1D4, a heavy chain variable region of the capture antibody comprises HCDR1-3 as shown in SEQ ID NO: 4-6, and a light chain variable region of the capture antibody comprises LCDR1-3 as shown in SEQ ID NO: 1-3; a detection antibody used by the kit is 3A6, a heavy chain variable region of the detection antibody comprises HCDR1-3 as shown in SEQ ID NO: 12-14, and a light chain variable region of the detection antibody comprises LCDR1-3 as shown in SEQ ID NO: 9-11. The double-antibody sandwich ELISA detection kit for detecting ApoE4 provided by the invention has no cross reaction with other subtypes of ApoEs, the used monoclonal antibody has high sensitivity, the kit can be used for screening glaucoma in physical examination and ophthalmic examination of old people, and the screening result is counted and summarized to a health information system and a cloud platform for big data analysis, so that the health condition of a patient can be detected.

This invention relates to a novel truncated mutant apolipoprotein E and its calibrators and quality control methods. The amino acid sequence of the truncated mutant apolipoprotein E is shown in SEQ ID. The diluent for the calibrators and quality control methods for detecting the truncated mutant apolipoprotein E includes a preservative, a protein protection composition, a surfactant composition, an ion stabilizer composition, and a buffer solution. The method for preparing the apolipoprotein E mutant includes the following steps: 1. Determining the specific sequence of the truncated mutant; 2. Determining that the mutation site is located at position 78 of wild-type apolipoprotein E; 3. Containing the NdeI site and the mutation sequence; locking the mutation; artificially optimizing the apolipoprotein E nucleotides using E. coli; 4. Extracting the corresponding truncated mutant by electrophoresis; 5. Obtaining the truncated mutant apolipoprotein E through recombination with E. coli. This invention solves the problems of discrepancies between detection results and actual clinical applications, as well as the poor stability of apolipoprotein E calibrators.

The present disclosure relates to double-stranded ribonucleic acid (dsRNAi) agents and compositions that target the APOE gene, and methods of using such dsRNAi agents and compositions to inhibit expression of the APOE gene and to treat subjects with APOE-associated neurodegenerative diseases or disorders, such as Alzheimer's disease and Parkinson's disease.

The application belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody combination for detecting apolipoprotein E4 and application thereof. The combination comprises monoclonal antibody 4E10 and monoclonal antibody 3H7, and the complementarity determining region (CDR) sequences thereof are shown as SEQ ID NO. 1 to SEQ ID NO. 12. In a double antibody sandwich ELISA, 4E10 is used as a coating antibody, and 3H7 is used as a labeled antibody, so that APOE4 subtypes can be effectively recognized, high specificity and high sensitivity detection of APOE4 can be realized, the detection limit reaches 100 pg / mL, and the method is suitable for quantitative detection of APOE4 in serum, cerebrospinal fluid and the like. The method provides a reliable immunological tool for early risk assessment of Alzheimer's disease, and has important clinical application value.

This invention discloses an antibody for detecting apolipoprotein E4 and its application, specifically involving a detection antibody and kit for detecting ApoE4, a blood marker of Alzheimer's disease. Based on this antibody and kit, the presence of apolipoprotein E4 can be accurately detected.

The invention discloses aromatic acid salt of apolipoprotein E mimetic peptide as well as a preparation method and medical application of the aromatic acid salt. The aromatic acid salt, namely the compound ZYH-76, regulates and controls miR-29a-5p, inhibits an iNOS / HMGB1 / TLR4 / MMP-9 signal channel, reduces polarization of A1 type astrocytes, promotes polarization of A2 type astrocytes and protects the integrity of a blood-brain barrier, so that hemorrhagic transformation (HT) after acute ischemic stroke is inhibited. The compound ZYH-76 has a remarkable drug effect in various HT animal models, excellent pharmacokinetic properties and high safety, can be prepared into a freeze-dried preparation for injection, is suitable for HT risk prevention and treatment, and has a good clinical application prospect.

The present invention relates to a C-terminal fragment (such as ApoE CT) of apolipoprotein E (ApoE) and modified ApoE2 and an application of the fragment in inhibiting γ-secretase activity. In one aspect, the present invention provides an isolated ApoE construct, which contains an ApoE polypeptide, the ApoE polypeptide: (1) contains a fragment from an amino acid sequence as shown by SEQ ID NO: 12, a first amino acid residue at a N-terminal of the fragment being an amino acid residue at any position between positions 215-221 of SEQ ID NO: 12, and a last amino acid residue at a C-terminal of the fragment being an amino acid residue at any position between positions 274-299 of SEQ ID NO: 12; or (2) the amino acid sequence has at least about 70% sequence identity with the fragment of (1), and retains at least about 50% of inhibition of the fragment of (1) against γ-secretase enzymatic digestion activity. The present invention further provides an encoding sequence, nucleic acid construct, host cell, construction method, pharmaceutical composition, and application of a protein portion of the ApoE construct.

The present invention relates to the field of neurodegenerative diseases, in particular Alzheimer's disease. The present invention further relates to fibrillary Apolipoprotein E (ApoE) for use in a method of treatment and / or prevention of a neurodegenerative disease and methods of producing said fibrillary ApoE. Moreover, the present invention relates to an antigen-binding peptide specifically binding to fibrillary ApoE, preferably human ApoE, a method of generating said antigen-binding peptide, and its use in a method of treatment and / or prevention and / or diagnosis of a neurodegenerative disease in a patient in need thereof.

The application discloses a method and a kit for simultaneously detecting multiple proteins in liver, and belongs to the technical field of medical detection. The target proteins of the method include glutamate amino transferase 1 protein, glutamic transaminase 1 protein, methionine adenosyltransferase 1A protein, glutathione peroxidase 1 protein, cytokeratin 18 and apolipoprotein E. First, the liver tissue to be detected is subjected to pretreatment such as enzymolysis and desalination to obtain a sample solution to be detected, then nanoliter liquid chromatography-tandem mass spectrometry is used to detect six characteristic peptide segments corresponding to the target proteins in the sample solution to be detected, and the content of the corresponding target proteins is calculated according to the content of the characteristic peptide segments. The method is convenient to operate, has good selectivity, high accuracy and high sensitivity, the detection limit reaches the pg / mL level, absolute quantification of the proteins can be realized, and the method has a wide application prospect in the research and development and efficacy evaluation of anti-liver injury drugs.

The present disclosure relates to methods for treating or alleviating a fetal alcohol spectrum disorder (FASD) in a subject, the method comprising administering to the subject an effective amount of an apolipoprotein E (APOE)-modulating therapeutic, thereby treating or alleviating the FASD.

The application discloses an arylate of apolipoprotein E mimetic peptide and a preparation method and medical application thereof. The arylate, namely compound ZYH-76, can inhibit hemorrhagic transformation (HT) after acute ischemic stroke by regulating miR-29a-5p, inhibiting an iNOS / HMGB1 / TLR4 / MMP-9 signal path, reducing polarization of A1 type astrocytes, promoting polarization of A2 type astrocytes and protecting integrity of a blood-brain barrier. The compound ZYH-76 has remarkable effects in various HT animal models, excellent pharmacokinetic properties and high safety, can be prepared into a freeze-dried preparation for injection and is suitable for HT risk prevention and treatment, and has a good clinical application prospect.

The present disclosure relates to a single nucleic acid for real-time detection for single nucleotide polymorphism (SNP) analysis of apolipoprotein E (ApoE) gene and a detection method using the same.

The invention belongs to the technical field of biological medicine, and relates to a method for preparing PAPA / siRNA nanoparticles by adopting a delivery carrier PAH-AM-PEG-ApoE (159-167) 2 (PAPA) modified by apolipoprotein E (ApoE) peptide through an electrostatic binding self-assembly method by designing and screening a siRNA sequence aiming at beta-site amyloid precursor protein cutting enzyme 1 (BACE1) and glycogen synthase kinase-3beta (GSK3beta) and adopting a delivery carrier PAH-AM-PEG-ApoE (159-167) 2 (PAPA) modified by ApoE peptide. The siRNA nano delivery system constructed by the invention aims to explore a new way for AD treatment.

This invention relates to a nucleic acid-lipid nanoparticle for enhanced liver and kidney targeting, its preparation method, and its application. The nucleic acid-lipid nanoparticle comprises lipid nanoparticles and a nucleic acid drug encapsulated therein. The raw materials for preparing the lipid nanoparticles include myristoylphosphatidylcholine, ionizable lipids, cholesterol, and triglycerides. The nucleic acid drug is an siRNA drug. Based on the crucial role of apolipoprotein E in liver-specific recognition and endocytosis, this invention enhances and predictably regulates liver delivery efficiency by modulating the interaction between the molecular structure of helper phospholipids in the lipid nanoparticles and apolipoprotein E, providing a general and scalable design strategy for liver-targeted delivery of nucleic acid drugs.

This invention discloses an immunochromatographic assay kit, preparation method, and application for the detection of apolipoprotein E4. The kit includes a test card and sample diluent. The test card comprises a test strip, which includes a PVC base, absorbent paper, a glass fiber pad, and a nitrocellulose membrane. The glass fiber pad is loaded with polystyrene latex microspheres for physical adsorption. The surface of the polystyrene latex microspheres is modified with sulfonyl or hydroxyl groups, and the zeta potential ranges from -15V to -20V. After the polystyrene latex microspheres are uniformly coated on a glass slide and dried, the contact angle between them and water droplets is greater than 90°. The nitrocellulose membrane is loaded with anti-APOE4 antibody, coating solution, and protein A. The sample diluent includes PBS, TWEEN-20, Tetronic 1307, and CHAPS. This invention eliminates the need for monoclonal antibody-labeled latex microspheres, reducing false positives and reagent batch-to-batch variation, and achieving higher sensitivity.

The application relates to the technical field of in-vitro diagnostic kits, and discloses an apolipoprotein E4 detection kit and application thereof. An immunochromatographic test paper comprises a detection immunochromatographic test paper, the detection immunochromatographic test paper comprises a bottom plate, a sample pad, a binding pad, an NC membrane and a water absorption pad, one side of the NC membrane is sequentially provided with the binding pad and the sample pad, and the other side of the NC membrane is provided with the water absorption pad; gold-manganese oxide nano color developing particles and apolipoprotein APOE4 monoclonal antibodies are marked on the binding pad. Through the technical scheme, the problems of complex operation, high cost, low detection sensitivity and weak specificity of apolipoprotein E4 detection in the related art are solved.

The invention discloses an oncolytic adenovirus for targeted therapy of brain tumors as well as a preparation method and application of the oncolytic adenovirus. The oncolytic adenovirus is modified by cholesterol, and the cholesterol is modified on the surface of the oncolytic adenovirus in a non-covalent binding mode. According to the invention, the oncolytic adenovirus is non-covalently modified by cholesterol, and an apolipoprotein E-mediated pathway is utilized, so that the blood-brain barrier and brain tumor targeting are efficiently spanned, the virus activity and the biological safety are maintained, and the advantages of immune remodeling and easiness in preparation are achieved.