70 results about "Klotho" patented technology

To provide a new composition for increasing expression of the Klotho gene and an application thereof.SOLUTION: The present disclosure provides, in one aspect, the following invention: a composition for enhancing expression of the human Klotho / KL gene, the composition comprising at least a portion of a protein belonging to the TNF superfamily or a nucleic acid encoding at least a portion of the protein.SELECTED DRAWING: None

The invention relates to a small extracellular vesicle containing Klotho protein and / or mRNA as well as a preparation method and application of the small extracellular vesicle. The preparation method of the small extracellular vesicle comprises the following steps: S1, constructing a recombinant expression vector containing a Klotho protein coding gene; s2, introducing the recombinant expression vector into recipient cells to obtain a receptor cell strain with stable expression of the Klotho gene; and S3, culturing the receptor cell strain, collecting a culture supernatant, and extracting the small extracellular vesicles from the culture supernatant. The small extracellular vesicles containing the Klotho protein and / or mRNA can regulate and control the expression of endogenous Klotho, the expression profile of bioactive molecules in the small extracellular vesicles is also changed, the small extracellular vesicles are rich in various kidney protective proteins, miRNA and other bioactive molecules, and the treatment effect on AKI and AD is remarkably enhanced.

The invention discloses a circRNA nano delivery system capable of reversing nucleus pulposus progenitor cell senescence and a preparation method and application of the circRNA nano delivery system. The circRNA nano delivery system comprises: a) Klotho circRNA, and b) a liposome, and the liposome comprises a vascular peptide vasculotide, an ionizable lipid molecule, a phospholipid, a PEG lipid, and a steroid. The invention also provides application of the circRNA nano delivery system capable of reversing nucleus pulposus progenitor cell senescence in preparation of drugs for treating intervertebral disc degeneration. The invention provides liposome particles (Vas-Klotho-LNP) which have targeted NPPCs and wrap circRNA, Klotho circRNA is efficiently introduced into the NPPCs through Tie2 agonist peptide, so that rejuvenation of the NPPCs is promoted, ECM synthesis is promoted, and regeneration and repair of intervertebral discs are synergistically promoted in vivo and in vitro.

The present invention relates to a compound for inducing the expression of the anti-aging gene klotho and a preparation method therefor. The compound represented by Chemical Formula 1, according to the present invention, has an excellent effect of increasing the expression level of the klotho gene which is a gene associated with aging, and thus can be useful for a pharmaceutical composition, cosmetic composition or food composition for preventing skin aging, inhibiting cellular senescence or preventing, treating alleviating a vascular aging-induced disease or a renal disease.

This invention relates to the field of cosmetics, and more particularly to active oligopeptides and their application in the preparation of anti-aging products. This invention provides an active oligopeptide with anti-aging activity, the amino acid sequence of which is shown in SEQ ID NO:1 and / or SEQ ID NO:4. This invention also provides an active oligopeptide (β1 and β1c) designed based on computational structural biology, targeting the β-Klotho FGF19 / / FGF21 and receptor-binding arm (RBA) region, and optimized for physicochemical properties, for use in skin anti-aging.

The invention provides a culture medium for improving Klotho protein secreted by mesenchymal stem cells and application of the culture medium, and particularly, the culture medium comprises a basic culture medium, statins and a ROCK inhibitor. The culture medium can effectively improve the Klotho protein secretion level of the mesenchymal stem cells, does not affect the biological activity of the mesenchymal stem cells, and ensures the biological function integrity of the mesenchymal stem cells; meanwhile, operation is easy, cost is low, and good clinical application value is achieved.

Provided are a bifunctional recombinant protein GIK for regulating the glycolipid metabolism and resisting aging, and a preparation method therefor. The recombinant protein GIK comprises an N-terminus, a middle section and a C-terminus. The N-terminus is an optimized human GLP-1 polypeptide having an amino acid sequence of SEQ ID NO: 1; the middle section is an Fc region of human IgG4 having an amino acid sequence of SEQ ID NO: 2; and the C-terminus is an s-klotho polypeptide having an amino acid sequence of SEQ ID NO: 3. The N-terminus is connected to the middle section via a connecting peptide 1 having an amino acid sequence of SEQ ID NO: 4; the middle section is connected to the C-terminus via a connecting peptide 2 having an amino acid sequence of SEQ ID NO: 5; and a signal peptide of human serum albumin having an amino acid sequence of SEQ ID NO: 7 is introduced at the N-terminus, such that a bifunctional recombinant protein that can be secreted and expressed in mammalian cells is obtained, and the bifunctional recombinant protein has an amino acid sequence of SEQ ID NO: 8.

The present invention relates to a novel anti-βKlotho antibody and its use.The anti-βKlotho antibody can be used for the treatment of diseases mediated by βKlotho or mediated by βKlotho-FGFR1c-FGF21, particularly metabolic disorders, such as type 1 diabetes, type 2 diabetes, dyslipidemia, nonalcoholic fatty liver disease (NASH), nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, metabolic syndrome, or obesity.

The present invention relates to a Klotho messenger-RNA (mRNA), wherein the mRNA has a 5' CAP region, a 5' un-translated region (5'-UTR), a coding region encoding a Klotho polypeptide, a 3' untranslated region (3'-UTR) and a poly-adenosine Tail (poly-A tail), wherein the Klotho polypeptide comprises the KL1 domain of human Klotho, preferably wherein the coding region encoding the Klotho polypeptide comprises an RNA sequence having at least 80 % sequence identity to SEQ ID NO: 1, and wherein the coding region encoding the Klotho polypeptide preferably has a GC content of at least 54 %.

A genetically modified mesenchymal stem cell including an exogenous nucleic acid including a Klotho encoding region operably linked to a promoter or promoter / enhancer combination, wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell. Also disclosed are methods of treating a patient including administering a therapeutically effective number of the genetically modified mesenchymal stem cells to the patient. The methods of treatment include treating the patient for a neurodegenerative disease; cancer; organ fibrosis; renal disease; age-related changes of organs or organ systems; to slow, reverse and / or inhibit aging; arteriosclerosis; dementia; diabetes mellitus; erectile dysfunction; autoimmune diseases or autoimmune-related diseases; an inflammatory disease of the lung and sepsis.

The invention provides a polypeptide composed of a sequence SEQ ID NO: 1 or a variant of the polypeptide, the sequence of the variant has at least 85% identity with the sequence SEQ ID NO: 1, and the polypeptide is used for prolonging the life of a subject. The invention also provides a nucleic acid sequence for coding the polypeptide, a gene construct containing the nucleic acid sequence or an expression vector containing the gene construct, which are used for the application. The polypeptides, nucleic acid sequences, gene constructs or expression vectors of the invention may be administered in the form of a pharmaceutical composition with at least one pharmaceutically acceptable excipient, diluent or carrier.

The present invention relates to a GP-pKlotho nano-drug, its preparation method and application. A GP organic molecule is used to wrap the Klotho plasmid, and then this nano-GP-pKlotho drug is used to restore the reduction of Klotho caused by acute / chronic kidney injury and to evaluate the therapeutic effect. After intravenous injection, GP-pKlotho is passively targeted to proximal epithelial cells of the kidney, releases the DNA of Klotho in the cells, and the DNA of Klotho enters the cell nucleus. Compared with the non-injected group, the optimized DNA of Klotho translates into 5-15 times more Klotho mRNA, and the Klotho protein increases by 3-8 times, showing strong therapeutic advantages in treating hypotension in ischemic kidneys and acute and chronic kidney injuries caused by cardiovascular surgery.

This document relates to methods and materials for assessing and / or using one or more senotherapeutic agents. In some cases, methods and materials for determining the efficacy of an anti-senescence treatment in a mammal (e.g., a human) are provided. For example, a level of one or more α-Klotho polypeptides in a sample (e.g., a urine sample) from a mammal (e.g., a human) can be used to determine the efficacy of the one or more senotherapeutic agents. In some cases, methods and materials for treating a mammal (e.g., a human) having a disease or disorder characterized by a reduced level of an α-Klotho polypeptide are provided. For example, one or more senotherapeutic agents and / or one or more inhibitors of a senescence-associated secretory phenotype (SASP) polypeptide can be administered to a mammal (e.g., a human) to increase a level of α-Klotho polypeptides within the mammal.

The objective is to provide a simple and indirect method for estimating the rate of senescent immune cells (the ratio of immune cells with high SAβgal expression levels among T cells whose surface marker is CD8-positive) using a small amount of blood sample. [Solution] This method estimates the rate of senescent immune cells using the relative expression levels of one or more selected from Granzyme K, α-Klotho, GDF15, PAI-1 (SERPIN1), and ferritin in the blood.

The present invention relates to a novel compound that induces the expression of the anti-aging gene klotho. The compound according to the present invention is not only excellent in the effect of increasing the expression level of the klotho gene, which is an aging-related gene, but also has a protective effect against oxidative stress in retinal pigment epithelial cells (RPE), and therefore can be usefully used as a pharmaceutical composition for preventing or treating macular degeneration, or a functional health food composition.

The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising Q-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

Provided herein are klotho polypeptide compositions and methods for improving cognitive function in an individual comprising treatment of with klotho polypeptides.

To provide a pig lacking the Klotho gene.SOLUTION: The present invention provides a genetically modified pig (Sus scrofa), where gene manipulation of a fertilized egg results in the knockout of the Klotho gene. The fertilized egg gene manipulation is genome editing. The genome editing includes, as the gRNA sequence, any one or any combination of five specific sequences. The knockout of the Klotho gene is a deletion of one or both alleles. The deletion of one or both alleles of the Klotho gene causes a frameshift mutation. The genetically modified pig exhibits phenotypes of arterial calcification and bone mass reduction.SELECTED DRAWING: Figure 3

The invention belongs to the field of medicines for treating rheumatoid arthritis, discloses application of Klotho in preparation of medicines for treating rheumatoid arthritis, and particularly relates to application of Klotho in improvement of the inflammatory state of rheumatoid arthritis by regulating a PI3K-AKT signal channel. Klotho can effectively improve clinical inflammation indexes of RA (rheumatoid arthritis). The Klotho can improve the inflammatory state of the RA by adjusting a PI3K-AKT signal channel. Animal experiments prove that Klotho can be applied to treatment of rheumatoid arthritis diseases.

This application relates to a snow tea extract, a method for preparing the snow tea extract, and its application. The method for preparing the extract includes the following steps: S1. Mixing pulverized snow tea raw materials with water at a mass ratio of 1:7-15 to obtain a first mixture; S2. Culturing Bacillus licheniformis on a culture medium to obtain a seed culture of the Bacillus licheniformis; S3. Using the seed culture as a fermentation broth, adding it to the first mixture at an inoculum of 1%-5%, and obtaining a fermented mixture after fermentation; S4. Filtering the fermented mixture, and concentrating and drying the filtrate to obtain the snow tea extract. The snow tea extract obtained in this application has an excellent promoting effect on the expression of the klotho gene in human fibroblasts and can be applied in products that improve skin health, filling a gap in the prior art.

Compositions comprising peptides and dimers thereof that exhibit anti-fibrotic activity and decrease cardiac fibrosis in patients with Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) are provided. In one embodiment the peptide is the KL1 domain of Klotho.

An albumin binding constructs that enhances the pharmacokinetic performance of therapeutic peptides and proteins, extending their half-lives and reducing administration frequency, is disclosed. The core peptide DICLPRWGCLW (SEQ ID NO: 1) is covalently linked to hydrophilic, flexible glycine-serine (Gly-Ser) linkers of the formula (ggs)xgg where X is 3 to 8 units. These linkers provide strong albumin binding (dissociation constant <20 nanomolar). Some constructs feature the GGSGGSGGSGGRLIEDICLPRGCLWEDD (SEQ ID NO: 4) peptide and allow fusion of active proteins like Klotho, maintaining biological activity and leveraging albumin's extended half-life. Constructs are produced using cellular expression systems (CHO, HEK293, Transgenic Insect Cells) for scalability. These constructs show prolonged half-lives comparable to at least 90% of native albumin. Klotho constructs using the albumin binder demonstrate FGF23 binding dissociation coefficients between 15-30 nanomolar essentially the same as natural Klotho Designed to minimize antigenicity, these constructs improve drug delivery efficacy and patient outcomes.

This invention discloses a recombinant plasmid pULK for treating renal fibrosis, its preparation method, and its applications. The recombinant plasmid pULK carries a Klotho-specific ligand peptide, a GGGGS flexible linker peptide, and a USP2 coding sequence tandemly in a 5'→3' configuration. The amino acid sequences are MASDPLGVVR, GGGGS, and the corresponding USP2 sequence, respectively. The preparation method includes fusion gene design and synthesis, vector linearization, recombinant construction and transformation, and positive clone verification. This plasmid can target and stabilize the Klotho protein, avoiding off-target risks, and can be used to prepare anti-renal fibrosis drugs. It is applicable to various chronic kidney diseases with renal fibrosis, filling a technological gap and demonstrating strong feasibility for clinical translation.

The present invention provides a polypeptide consisting of the sequence of SEQ ID NO: 1, or a variant thereof consisting of a sequence at least 85% identical to SEQ ID NO: 1, for use in the prevention and / or treatment of a muscle disease or disorder. The present invention also provides a nucleic acid sequence encoding the polypeptide, a gene construct comprising the nucleic acid sequence, or an expression vector comprising the gene construct, for said use. The polypeptide, nucleic acid sequence, gene construct, or expression vector of the present invention may be administered in the form of a pharmaceutical composition, together with at least one pharmaceutically acceptable excipient, diluent, or carrier. The present invention also provides non-therapeutic methods for improving muscle function and / or increasing muscle mass in a subject.

This invention relates to the field of cosmetics, and more particularly to oligopeptides and their application in the preparation of anti-aging products. This invention provides an oligopeptide with anti-aging activity, the amino acid sequence of which is shown in any of SEQ ID NO:1 to SEQ ID NO:3. This invention rationally designs and optimizes three α-Klotho-derived oligopeptides (RBA-1, RBA-1d, and RBA-1e) with a clear structural basis and optimized physicochemical properties through high-resolution crystal structure information of the FGF23-FGFR1c-αKlotho ternary complex, systematic truncation screening of the receptor binding arm (RBA), and conformation prediction, for use in skin anti-aging.

A fusion protein and a use thereof. The fusion protein comprises an FGF21 mutant protein. The FGF21 mutant protein comprises modifications based on a wild-type human FGF21 sequence, the modifications being: deletion of a proline residue at position 171, or formation of a pair of disulfide bonds before and after the proline residue at position 171 by means of substitution, deletion, or addition of one or more amino acid residues. The FGF21 mutant protein is resistant to enzymatic degradation at the C-terminus thereof by a fibroblast activation protein (FAP), maintains C-terminus activity for binding to a β-klotho receptor, thereby extending an in vivo half-life and the pharmacological effect. The fusion protein enhances the therapeutic efficacy thereof in weight loss, blood glucose reduction, and non-alcoholic steatohepatitis (NASH) by fusing the FGF21 mutant protein with other molecules, such as GLP-1.

This invention relates to compositions for the prevention or treatment of degenerative neurological diseases, comprising a compound that induces the expression of the anti-aging gene klotho as an active ingredient. The compound of this invention, expressed by chemical formula 1, exhibits excellent efficacy in increasing the expression level of the Klotho gene, a gene related to aging, and can be effectively used as a pharmaceutical composition or food composition for the prevention, improvement, or treatment of degenerative neurological diseases.

Provided herein are klotho polypeptide compositions and methods for improving cognitive function in an individual, including treatment with a klotho polypeptide.

The present disclosure provides: a gene construct comprising a nucleic acid sequence encoding a mammalian s-KL, which nucleic acid sequence is operatively linked to a muscle cell specific promoter, the present invention relates to gene constructs for use in the treatment of dyskinesia, which may be expressed, for example, in neuromuscular disorders or diseases, using viral and non-viral vectors having myoblast and motoneuron tropies, containing gene constructs, which are useful in the treatment of dyskinesia, which may be expressed, for example, in neuromuscular disorders or diseases, the gene construct contains a nucleic acid sequence for coding mammalian s-KL, and the nucleic acid sequence is operatively connected with a promoter such as a muscle cell specific promoter and is delivered in a pharmaceutical composition containing an expression vector; an isolated cell containing the expression vector; and methods of treating dyskinesia and motor neuron diseases.

This disclosure provides engineered α-klotho polypeptides and methods for their production and use. The soluble α-klotho polypeptides disclosed herein comprise an α-klotho moiety having one or more mutations relative to human α-klotho for enhanced activity, productivity, and / or stability. This disclosure further provides pharmaceutical compositions comprising the engineered α-klotho polypeptide, and methods for using the engineered α-klotho polypeptide in treatments, including the treatment of age-related conditions and kidney disease. Also disclosed are nucleic acids encoding the engineered α-klotho polypeptide, recombinant cells expressing the engineered α-klotho polypeptide, and methods for producing the engineered α-klotho polypeptide.