96results about "Apolipeptides" patented technology

The present invention relates to high density lipoprotein (HDL) or HDL mimetics for use in the prevention and / or treatment of graft-versus-host disease (GvHD) or cytokine release syndrome in a subject.

Methods of treating age-related macular degeneration (AMD) may include the administration of amphipathic, ATP binding cassette transporter membrane agonists to reduce the amount of drusen in the subject in need thereof. These methods may be particularly useful for treatment of intermediate AMD.

The invention relates to the technical field of biology, in particular to a promoter with real skin specificity and application thereof. The promoter provided by the invention is selected from a promoter of any one or more of the following genes: GPN, FOS or APO. The promoter with true skin specificity provided by the invention can specifically express a target gene in dermis and remove off-target expression of liver and subcutaneous lipid membrane muscle at the same time, the promoter sequence is shorter than that of a broad-spectrum promoter, and the human hGPN promoter can be more safely applied clinically.

To provide a new immunotherapeutic agent useful for treating obesity.SOLUTION: The pharmaceutical composition contains a peptide having a specific amino acid sequence containing a B cell epitope. Preferably the composition includes an aluminium salt (Alhydrogel (Al (OH) 3) and monophosphoryl lipid A as adjuvants. Intramuscular administration of the composition to a subject results in the production of antibodies capable of binding to ApoB-100 in vivo, and the antibodies exert a therapeutic effect on obesity.SELECTED DRAWING: Figure 14

A method of treating leukocytosis, endothelial dysfunction, and carditis comprising administering to a subject a lipid-binding protein-based conjugate.

The invention relates to modified apolipoprotein with a targeting body. The targeting body may for example be an antibody or antigen binding fragment that allows targeting of e.g. a specific cell, tissue or organ. The modified apolipoprotein can be used as a carrier for a payload as such or when incorporated in a lipid nanoparticle. The modified apolipoprotein finds use in the treatment or prevention of diseases, or targeting a pay load to a specific target site.

Provided herein are gene editing systems and compositions directed to effectuate in vivo edits in the LPA gene. Treatment or prevention of cardiovascular disease through disruption of the production of apo(a) through genetic editing and the reduction of the blood lipoprotein(a) [Lp(a)] concentration is disclosed herein. Disclosed are nickase-based gene editing systems designed to effectuate the installation of insertions and / or deletions (indel variants) and / or non-synonymous variants in the coding sequence of LPA. The nickase-based gene editing systems generally comprise one or more mRNAs that encode one or more nickases and a plurality of guide oligonucleotides (e.g., gRNAs) and may be delivered in vivo to a mammalian subject in need thereof via a suitable delivery system, such as lipid nanoparticles (LNPs) (with or without GalNAc targeting moieties) intravenously, or otherwise, administered to a patient as potentially a once-and-done therapeutic. The manufacturing, use, and formulation of the gene editing systems and compositions are also disclosed.

The application belongs to the technical field of medicine, and particularly relates to a liver damage biomarker for judging whether a newborn male piglet is affected by intrauterine growth restriction. The application discloses application of APOA4 as a biomarker for judging whether a male piglet is affected by intrauterine growth restriction. Expression of APOA4 in serum and liver biopsy tissue samples of a male piglet to be detected is determined; when APOA4 is abnormally up-regulated, it is judged that the male piglet to be detected is a male piglet affected by intrauterine growth restriction.

The present disclosure relates to engineered phospholipid or lysophospholipid (e.g., sphingosine 1-phosphate (S1P)) chaperones derived from apolipoprotein M (ApoM)-Fc fusion proteins with extended half-life in vivo. The disclosed ApoM-Fc fusion proteins provide a safe, highly efficient and effective way of delivering S1P to endothelial cells and all tissues of the body.

Provided herein are engineered fusion proteins comprising ApoM (e.g., human or murine ApoM) fused to a constant region (Fc) of a immunoglobulin G (IgG, e.g., human IgG or murine IgG). In some embodiments, the ApoM-Fc fusion protein further comprises a signal peptide (e.g., IL-2 signal peptide) fused to the ApoM, allowing the fusion protein to be secreted once expressed recombinantly. Methods of using the ApoM-Fc fusion protein or the sponge variants in the treatment of various diseases or disorders are provided.

Provided are a nucleic acid construct for achieving modular loading of an engineered EVs functional protein and use of said construct. A modular design principle is adopted, specific modules are selected for combination, a mutant sequence is optimized and screened to obtain an improved nucleic acid construct, and finally, the engineered EVs modularly loaded with functional protein is converted and expressed. The product has the following advantages that: I) the modular loading of the engineered EVs functional protein is achieved; 2) the loading density and the loading efficiency of the protein inside and outside an EVs membrane are improved; and 3) a specific support sequence module is selected to avoid enzyme digestion. The construct is used to prepare the engineered EVs, so that the modular loading of the functional protein can be achieved, the loading efficiency is improved, and the construct has a wide clinical application value and market prospect.

Provided herein are compositions and methods for modifying the human gene, APOC3. Such compositions and methods may result in the reduction of the protein, apolipoprotein C3 (apoC-III) when administered to a human subject. Compositions and methods provided herein may comprise a CRISPR-associated (Cas) protein or uses thereof. Compositions and methods of the present disclosure may be useful for treatment of APOC3 associated conditions, including persistent chylomicronemia, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG).

Compositions and methods for treating age-related macular degeneration (AMD) are described herein. In particular, polypeptides comprising a helix structure having ATP-binding cassette transporter membrane stabilization and agonist activity, transporter protein binding activity, and / or capable of effecting cholesterol efflux, and methods of using these peptides for treating AMD are described herein.

This invention relates to antibody-binding lipid nanoparticles comprising antibodies bound to membrane scaffold proteins, and more specifically, to antibody-binding lipid nanoparticles comprising lipids and antibodies bound to membrane scaffold proteins, which are therefore easy to prepare and have excellent specific targeting capabilities.

The present disclosure provides a therapeutic nanodisk, the therapeutic nanodisk comprising: a lipid-binding polypeptide; a lipid bilayer and a therapeutic agent, wherein the therapeutic agent may be of use for treating, preventing a central nervous system disease, disorder, trauma or injury; or as a diagnostic agent for diagnosing a central nervous system disease, disorder, trauma or injury. The lipid bilayer may be 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the therapeutic agent may be a nucleic acid polymer. Further provided are methods for administration of the therapeutic nanodisk to treat, prevent or diagnose the central nervous system disease, disorder, trauma or injury and uses of such therapeutic nanodisks.

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.

To provide oligomeric compounds with conjugate groups targeting apolipoprotein(a).SOLUTION: Provided is an oligomeric compound for use in treating or preventing a disease or condition in a human, the oligomeric compound being ISIS 681257, the treatment comprising administering at most 500 mg of the oligomeric compound to the human during a dosing period.SELECTED DRAWING: Figure 1A

The invention relates to fusion proteins of apolipoprotein with an immunomodulatory biomolecule and / or a rerouting molecule. The fusion proteins can be used as a carrier for an immunomodulatory biomolecule as such or incorporated in a lipid nanoparticle. The fusion protein finds use in the treatment of immune related disorders, or targeting a payload, such as a nucleic acid, to a specific target site.

This invention discloses a gene editing system for constructing a porcine nuclear transplantation donor cell model of atherosclerosis with double gene mutations in AF and its applications. The invention provides a kit comprising plasmid pKG-U6gRNA (APOE-E2-gRNA2), a target sequence binding region as shown in nucleotides 3-22 of SEQ ID NO: 25 (FBN1-gRNA4), a target sequence binding region as shown in nucleotides 3-22 of SEQ ID NO: 26 (FBN1-gRNA6), and FBN1-mutant-ss163 as shown in SEQ ID NO: 27. The kit is used for: preparing recombinant cells; preparing porcine atherosclerosis models; preparing atherosclerosis cell models, atherosclerosis tissue models, or atherosclerosis organ models. The plasmid pKG-U6gRNA (APOE-E2-gRNA2) is transcribed to obtain sgRNA with a target sequence binding region as shown in nucleotides 1-20 of SEQ ID NO: 11. APOE‑E2‑gRNA2 This invention lays the foundation for developing pig models of atherosclerosis through somatic cell nuclear transfer animal cloning technology.

The present disclosure provides methods and compositions for the treatment of Alzheimer' s disease. The methods and compositions of the present disclosure comprise AAV vectors and AAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for an APOE2 polypeptide.

Provided herein are compositions and methods for modifying the human gene, APOC3. Such compositions and methods may result in the reduction of the protein, apolipoprotein C3 (apoC-III) when administered to a human subject. Compositions and methods provided herein may comprise a CRISPR-associated (Cas) protein or uses thereof. Compositions and methods of the present disclosure may be useful for treatment of APOC3 associated conditions, including persistent chylomicronemia, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG).

Disclosed herein are methods and compositions useful in screening a compound for its effect on proteotoxicity and proteinaceous inclusions involved in neurological disease.

Aspects of the disclosure relate to compositions and methods for multiplexed gene silencing in a cell or subject. In some embodiments, the disclosure provides an isolated nucleic acid or an rAAV encoding a transgene comprising a RNA-guided nuclease (RGN) operably linked to a first promoter, and a second promoter operably linked to a multi guide-RNA (multi-gRNA) expression cassette encoding one or more gRNAs targeting a gene associated with hypercholesterolemia or dyslipidemia. In some embodiments, the disclosure provides methods of treating a subject having hypercholesterolemia or dyslipidemia by administering the compositions.

Provided are molecular hooks that are capable of tethering a protein of interest to a high-density lipoprotein (HDL) molecule. Also provided are methods of intracellular protein delivery to cells and organisms using the molecular hooks of the present disclosure. Such methods provide several advantages including the ability to intracellularly deliver the protein of interest to tissues behind the blood-brain barrier, and not requiring extreme cold temperatures for storage or transport.

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 provides methods and compositions for the treatment of Alzheimer's disease. The methods and compositions of the present disclosure comprise AAV vectors and AAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for an APOE2 polypeptide.

The present disclosure provides methods of treating Alzheimer's Disease (AD) and rescuing cognitive deficits associated with AD in a subject having an apoE4 / 4 genotype, by administering a therapeutically effective amount of the loop-diuretic bumetanide to the subject. Also disclosed are kits for performing the method, including one or more doses of a bumetanide formulation; and which may also include instructions for treating a patient having an apoE4 / 4 genotype by administering bumetanide, and / or instructions and reagents for testing / identifying a subject having an apoE4 / 4 genotype.

To provide a therapeutic agent for dilated cardiomyopathy disease which produces excellent effects in treatment of dilated cardiomyopathy (DCM) and provides a given benefit to a large number of patients.SOLUTION: The present invention provides a therapeutic agent for dilated cardiomyopathy comprising at least one selected from a group consisting of mesenchymal stem cells and microparticles derived from the mesenchymal stem cells. It is preferable that the mesenchymal stem cells are cells having ability to contain or secrete microparticles, that the microparticles have an average particle size of 1000 nm or less, and that they are exosomes.SELECTED DRAWING: None