53 results about "Telomerase" patented technology

The invention provides a DNA library screening method and application of an intracellular mRNA sensor switch. The DNA library screening method comprises the following steps: designing a DNA library containing a switch sequence of a degenerate basic group; preparing a circular expression vector library; preparing a minimum linear expression vector library; performing seamless cloning; carrying out RCA rolling circle amplification; carrying out telomerase digestion; carrying out cell transfection; extracting RNA (Ribonucleic Acid) and carrying out reverse transcription; carrying out library building of next-generation sequencing by taking the cDNA as a template; carrying out next-generation sequencing; analyzing data and comparing to obtain the DNA library of the mRNA sensor switch. According to the DNA library screening method provided by the invention, more sensor switch sequences can be provided for a single site on mRNA in cells, and more selection possibilities are further provided for subsequent targeted therapy.

The present disclosure relates to methods of treating myelodysplastic syndrome. The present disclosure provides methods of treating myelodysplastic syndrome (MDS) in a subject not treated with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The methods comprise administering to the subject an effective amount of a telomerase inhibitor, such as, for example, imestat or imestat sodium. In some cases, a subject being treated is classified as a low or moderate-1IPSS risk MDS subject and / or has an erythropoiesis stimulating agent (ESA) recurrent / refractory MDS.

The invention provides a recombinant herpes simplex virus and a herpes simplex virus modification method. The herpes simplex virus modification method comprises the step of replacing an ICP4 protein coding gene in a herpes simplex virus genome containing an infected cell protein 4 (ICP4) gene with an hTERTp-fluorescent protein expression cassette. The expression cassette comprises an hTERTp promoter and a fluorescent protein coding sequence controlled by the hTERTp promoter, and the transcription direction is opposite to that of an ICP4 promoter in a genome. The hTERTp-fluorescent protein expression cassette in the recombinant virus obtained by the method disclosed by the invention can be normally expressed in response to telomerase activity. Therefore, the recombinant virus is capable of expressing a fluorescent protein, such as mBaoJin, in a cell having human telomerase activity. Cells infected by the virus can be identified through fluorescence signals, and the higher the telomerase activity is, the stronger the fluorescence intensity is. The virus has wide application value in research of tumor action mechanisms and stem cell action mechanisms, health assessment, screening of tumor drugs, research and development of diagnostic reagents and establishment of animal models.

The present disclosure provides transgenic mice for use as mouse models, and methods related thereto. The transgenic mice described herein comprise a humanized mouse telomerase (hmTert) gene included in a background mouse germline that provides shortened telomeres capable of reproducing humans and various human disease states.

The application discloses application of falcarinol-7-methyl ether and derivatives thereof in preparation of medicines and functional foods for delaying aging or immune regulation. In the application, the falcarinol-7-methyl ether and derivatives thereof are derived from falcarinol-7-methyl ether, and can effectively delay replicative senescence of mesenchymal stem cells, inhibit expression of aging-related markers of mouse liver and lung induced by adriamycin, improve grip strength of the mouse, enhance muscle function, and promote proliferation of T cells separated from human peripheral blood mononuclear cells, and have an immune regulation effect. Therefore, the falcarinol-7-methyl ether and derivatives thereof have good effects of improving telomerase activity, anti-aging and immune regulation, and can be developed into anti-aging or immune regulation products.

The invention belongs to the field of food science and engineering, and discloses a preparation method of an active medicinal and edible composite nutrient AMCN with an anti-aging effect, and the preparation method comprises the following steps: putting a ganoderma lucidum monoclonal strain into a liquid culture medium for controllable culture to obtain supernate with beta-glucosidase activity of over 100mU / mL; and adding rhizoma polygonati powder, lucid ganoderma powder and mulberry leaf powder, carrying out enzymatic biotransformation, carrying out lactobacillus plantarum fermentation, adding a freeze-drying protective additive, carrying out freeze-drying, grinding to obtain the active medicinal and edible composite nutrient AMCN, and storing the finished product in a dry and dark place. The active medicinal and edible composite nutrient can be used for preparing anti-aging functional foods or nutritional health-care products. A D-galactose induced zebrafish aging model verifies that the active medicinal and edible composite nutrient prepared by the application plays an anti-aging role by relieving oxidative stress, inhibiting cell aging and maintaining telomere stability, can reduce beta-galactosidase activity and intracellular ROS (reactive oxygen species) level, improves telomerase protein concentration, and has a good anti-aging effect. And the telomere length can be effectively recovered by medium and high concentrations.

This disclosure provides methods of treating a myelodysplastic syndrome (MDS) in a subject that is naive to treatment with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The method includes administering to the subject an effective amount of a telomerase inhibitor, such as e.g. imetelstat or imetelstat sodium. In some cases, the subject treated is classified as low or intermediate-1 IPSS risk MDS and / or have MDS relapsed / refractory to Erythropoiesis-Stimulating Agent (ESA).

The application provides a DNA library screening method of intracellular mRNA sensor switch and application. The DNA library screening method comprises the following steps: designing a DNA library containing a switch sequence with a complementary base; preparing a circular expression vector library; preparing a minimized linear expression vector library; seamless cloning; RCA rolling circle amplification; telomerase enzyme cutting; cell transfection; RNA extraction and reverse transcription; library construction by performing second-generation sequencing with the cDNA as a template; second-generation sequencing; data analysis and comparison, and obtaining the DNA library of the mRNA sensor switch. The DNA library screening method provided by the application can provide more sensor switch sequences for a single site on intracellular mRNA, and further provides more selection possibilities for subsequent targeted treatment.

Disclosed are use of a circRNA molecule as a diagnostic marker in a cell senescence diagnosis kit, and use thereof as a treatment target for cell senescence. The present invention finds that circHERC1 is lowly expressed in both cell models of natural senescence and induced senescence. Overexpression of circHERC1 in endothelial cells can improve the proliferation capacity of the endothelial cells, effectively extend the telomere length of the cells, activate telomerase, reduce the β-galactosidase positive rate of the cells, and reduce the expression of all senescence-associated proteins. Introduction of exogenous circHERC1 into mice can effectively delay the senescence of various organs and the shortening of telomeres in aged mice and reduce the β-galactosidase positive rates of various organs of aged mice.

The present invention relates to a drug delivery composition comprising a telomerase activator and nanoparticles, and a composition for preventing, improving, or treating hair loss comprising the same. More specifically, the present invention relates to a nanoliposome, nanosilica particle, or nanobubble composition encapsulating drugs such as the plant extract component TA-65 and its derivatives that increase telomerase activity, the telomerase activating compound GPC and its derivatives, and having the efficacy of promoting the regeneration and growth of hair follicles.

This disclosure provides methods of treating a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in a subject in need thereof, wherein the subject treated is classified as having an intermediate-2 or high IPSS risk MDS or AML; or has MDS or AML relapsed, refractory, or intolerant to HMA, venetoclax, or a combination thereof. The method includes administering to the subject an effective amount of a telomerase inhibitor or a pharmaceutically acceptable salt thereof, such as e.g. imetelstat or imetelstat sodium.

The present invention is directed to methods and uses of a series of compounds and compositions comprising the same for treating diseases, disorders and / or conditions related to fertility and preserving same and conditions related to same. In some aspects, the compounds and or compositions as herein described promote, improve, recover or restore fertility in a subject in need thereof, including in male and / or female subjects. Such methods / uses include promoting, enhancing or improving fertility-associated cell or tissue yield as part of an in vitro fertilization protocol.

Provided herein are compounds and isolated enantiomers useful for inhibiting telomerase, pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising at least one such compound, isolated enantiomer, or pharmaceutically acceptable salt thereof. Also described is the use of such compounds, isolated enantiomers, or pharmaceutically acceptable salts thereof, and the use of pharmaceutical compositions comprising at least one such compound, isolated enantiomer, or pharmaceutically acceptable salt thereof, in methods of treating disorders or conditions such as cancer, where the cancer may be a hematological malignancy or a solid tumor.

This invention discloses a protein-degrading DNA material, its preparation method, and its applications. The protein-degrading DNA material includes a degradation initiation module, a protein targeting module, and a response module. The degradation initiation module is an E3 ubiquitin ligase targeting module, and the response module is a telomerase response module. The preparation method includes the following steps: dissolving the ssDNA strand used in the degradation initiation module in a solvent and annealing it to obtain the degradation initiation module; dissolving the ssDNA strand used in the protein targeting module in a solvent and annealing it to obtain the protein targeting module; dissolving the ssDNA strand used in the response module in a solvent and annealing it to obtain the response module; and mixing the degradation initiation module, the protein targeting module, and the response module to obtain the protein-degrading DNA material. The protein-degrading DNA material of this invention possesses tumor microenvironment triggering characteristics, can precisely target tumor cells, and has a high efficiency in degrading pathogenic proteins.

The invention provides a recombinant herpes simplex virus and a preparation method thereof. The preparation method comprises the step of replacing an original ICP4 coding sequence in a herpes simplex virus genome containing an infected cell protein 4 (ICP4) gene with an hTERTp-ICP4-fluorescent protein expression cassette. The expression cassette comprises an ICP4 coding sequence and a fluorescent protein coding sequence under the control of an hTERTp promoter, and the transcription direction of the expression cassette is opposite to that of an original ICP4 promoter. The recombinant viruses are capable of selectively replicating and indicating telomerase activity in cells having human telomerase activity. Cells infected by the virus can be identified through fluorescence signals, and the higher the telomerase activity is, the stronger the fluorescence intensity is. The virus has wide application value in research of tumor action mechanisms and stem cell action mechanisms, health diagnosis, immune assessment, screening of tumor drugs, research and development of diagnostic reagents and establishment of animal models.

According to the TelN prokaryotic telomerase variant and the preparation method thereof, compared with wild type TelN prokaryotic telomerase, the TelN prokaryotic telomerase variant has the advantages that the activity is obviously improved, and the TelN prokaryotic telomerase variant has a good industrial application prospect.

The present invention provides methods and kits for determining telomerase processivity. These methods and kits may be used to screen for drugs that inhibit or enhance telomerase repeat addition activity, and are readily adapted to an ultra-high-throughput format.

This invention relates to the NBLS (Niobium Bovine Kidney Cell Line), with accession number CCTCC NO: C2022197. This invention also provides its application in culturing BVDV virus. This invention successfully introduced the SV40-LT gene into primary Niobium Bovine Kidney Cells, activating their telomerase activity and extending the cell lifespan in vitro. Experiments showed that the NBLS Niobium Bovine Kidney Cell Line of this invention can be passaged for more than 50 generations without changing its growth and proliferation characteristics, thus obtaining an immortalized cell line. This F50 generation Niobium Bovine Kidney Cell Line NBLS is highly sensitive to BVDV virus and can efficiently proliferate the virus. The virus titer proliferated using this cell line shows increased sensitivity compared to primary Niobium Bovine Kidney Cells, reducing production costs. Therefore, this invention provides a new technical means for the large-scale production of BVDV vaccines.

The invention discloses an R-configuration telomerase inhibitor and application thereof, and belongs to the technical field of medicinal chemistry. The prepared R-configuration telomerase inhibitor has telomerase inhibition activity obviously superior to that of a racemate of the R-configuration telomerase inhibitor, and the anti-tumor activity of the R-configuration telomerase inhibitor in various tumor cell lines is obviously higher than that of the racemate of the R-configuration telomerase inhibitor. Meanwhile, the R-configuration telomerase inhibitor has a definite effect of remodeling an anti-tumor immune microenvironment in vivo, can effectively inhibit tumor progression and induce tumor tissue regression when being combined with a PD-L1 inhibitor, is high in safety, and provides a theoretical basis for combined immunotherapy.

An anti-aging traditional Chinese medicine composition and its preparation method belong to the field of traditional Chinese medicine technology. The composition consists of the following components by weight: 3-60 parts of Polygonatum sibiricum, 1-70 parts of Astragalus membranaceus, 2-40 parts of Lycium barbarum, and 1-40 parts of Ganoderma lucidum spore powder. The method is as follows: soak the raw materials except for Ganoderma lucidum spore powder; decoct the raw materials 1-3 times; combine the decoctions obtained after several decoctions and concentrate them to obtain concentrated decoction; prepare the concentrated decoction into freeze-dried powder; add Ganoderma lucidum spore powder to the freeze-dried powder and stir evenly. The pharmacodynamic research results of the anti-aging of the present invention are as follows: (1) The test drug can significantly prolong the average lifespan of naturally aging nematodes by 30%, which is better than Erjingwan and the Western medicine NMN; (2) improve exercise, feeding ability and nervous system function; (3) improve antioxidant capacity: reduce the fluorescence intensity of ROS and lipofuscin, and improve the survival rate of nematodes after H2O2 stress stimulation; (4) improve telomerase activity; (5) improve cognitive dysfunction and learning and memory ability.

The invention relates to a porphyrin-G quadruplex compound and application of the porphyrin-G quadruplex compound in diagnosis and treatment of tumors. Specifically, the invention provides a nucleic acid nanocluster, which comprises a nucleic acid aptamer AS1411G-quadruplex sequence and a human telomerase-derived G-quadruplex sequence, and can be used for loading porphyrin molecules, such as a photosensitizer Ce6 and Hem with a peroxidase-like effect, so that a porphyrin-nucleic acid nanocluster compound is obtained, and the effect of diagnosing and / or treating tumors is achieved. The nucleic acid nanocluster provided by the invention has better targeting property, stability and higher drug loading capacity. The nucleic acid nanocluster loaded with Ce6 and Hem can realize a synergistic effect of multiple functions, and has an enhanced tumor inhibition function.

This document provides a composition comprising telomerase or a functional fragment thereof and / or a telomerase activator, wherein the composition further comprises components for a gene editing system. Methods for improving gene editing efficiency and methods for editing genes in subjects are also provided.

For example, to provide a method for identifying or selecting patients who are most likely to benefit from treatment with telomerase inhibitors such as imetelstat. [Solution] This disclosure provides a method for identifying or selecting patients who are most likely to benefit from treatment with telomerase inhibitors, such as imetelstat, by testing for high molecular weight risk (HMR) based on the absence of mutations in each of JAK2, CALR, and MPL, and / or the presence of a mutation in at least one of the following genes: ASXL1, EZH2, SRSF2, and IDH1 / 2. These patients may have myelofibrosis. This disclosure also provides a method for treating myelofibrosis, the method of which includes identifying such patients.

The application relates to the technical field of medicines, in particular to a novel quinoline DKC1 inhibitor and application thereof. 23 H 26 ClN3O, a structure formula is shown as formula I. The compound can be directly and efficiently combined with an ASP125 site of DKC1 protein which is an important component of a telomerase, and effectively inhibit the pseudouridine synthase activity. Functional experiments show that the compound can significantly inhibit the proliferation ability of various DKC1 high-expression tumor cells by targeting inhibition of DKC1, and can produce better anti-tumor ability in combination with an ATR inhibitor, and exhibits potential value as a novel targeted therapeutic drug.

The invention discloses a medicinal and edible composition for improving muscle attenuation of old people, the composition comprises fructus piperis longi and radix asparagi extracts, and the composition is combined with highland barley, common turnip, maca, D-psicose and other active substances to develop a series of medicinal and edible compositions for improving muscle attenuation. The composition disclosed by the invention has a good protective effect in improvement of old-age muscle attenuation, and can be applied to muscle attenuation and exercise ability decline accompanied by aging, so that the activity of telomerase is enhanced; meanwhile, the traditional Chinese medicine composition is helpful for adjusting the proportion of immune cell subtypes, improving functional activity decline of an immune system and reducing chronic low-level inflammation states, and has both safety and effectiveness. Molecular mechanism research shows that the compound activates glutathione metabolism and inhibits ferroptosis signals to reverse skeletal muscle cell senescence. The composition disclosed by the invention can be developed into foods and health-care products for improving muscle mass, volume, strength and functions, and has a very good application prospect.

A consensus sequence of the antigen telomerase (ConTRt) can be generated and used in preventive and therapeutic vaccination. The consensus sequence of telomerase was generated by the fusion of two sequences, one belonging to human telomerase (hTERT) and the other to dog telomerase (dTERT), with the aim of developing an effective vaccine for the treatment of tumors expressing both human and dog telomerase, hence in both the human and veterinary sectors.

This disclosure provides methods of treating a myelodysplastic syndrome (MDS) in a subject who has not previously been treated with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The method includes administering to the subject an effective amount of a telomerase inhibitor, such as, for example, imetelstat or imetelstat sodium. In some cases, the subject being treated is classified as IPSS low or intermediate-1 risk MDS and / or has relapsed / refractory MDS to erythropoiesis stimulating agent (ESA).

The invention discloses a medicinal and edible composition for delaying cognitive and memory function decline of old people, which comprises a fructus piperis longi extract, a radix asparagi extract and sodium hyaluronate, and is combined with highland barley, common turnip, maca, D-psicose and other active substances to prepare the medicinal and edible composition for delaying cognitive and memory function decline of old people. A series of medicinal and edible compositions for improving cognitive and memory function decline of old people are developed. The composition disclosed by the invention has a good protective effect in delaying senile cognitive and memory function decline, can be applied to senile cognitive and memory function decline accompanied by age increase, enhances the activity of telomerase, and improves neurotransmitter homeostasis and brain health. Molecular mechanism research shows that the compound can reverse senescence of neuronal cells of hippocampus by activating key targets in a phosphatidylinositol-3-kinase / protein kinase B signal channel. The composition can be used for being developed into food and health care products for improving attention, learning ability, language ability and judgment, has safety and effectiveness, and has a very good application prospect.

A composition comprising a recombinant probiotic organism engineered to constitutively express an enzyme involved in maintaining telomere length, wherein the enzyme comprises a telomerase subunit, the genetic modification comprises an operon comprising a gene sequence encoding telomerase having a promoter recognized by the RNA polymerase of the probiotic organism and a genetic modification that induces the secretion of telomerase into the host organism, and the genetic modification of the telomerase gene sequence enhances the entry of the telomerase enzyme into the host organism's cells.

The invention discloses a viral vector for accurately regulating and controlling a human telomerase gene by using a human interleukin-6 core promoter and application of the viral vector. The virus vector comprises an expression cassette with a human interleukin-6 core promoter sequence and a human telomerase gene sequence, and the human interleukin-6 core promoter sequence is activated in a natural physiological process of cell aging and inhibited in a normal cell physiological state; further accurately regulating and controlling the human telomerase gene to be expressed as telomerase protein; according to the invention, a human interleukin-6 core promoter and a human telomerase gene (hT) are respectively inserted into a virus vector to obtain the virus vector, and after the virus vector is transfected into human tissue cells, the aging of the cells can be delayed. According to the invention, the human interleukin-6 core promoter is utilized to dynamically and accurately regulate and control the expression of the human telomerase gene and construct the expression cassette and the virus vector, so that the expression cassette and the virus vector have a wide application prospect in the anti-aging and aging-related fields.