34 results about "Antagomir" patented technology

Provided are methods for the modulation of chronic visceral inflammation in a cell, tissue, organ and / or subject using miRNA agents. Also provided are miRNA agents (e.g., miRNA, agomirs, and antagomirs) that can modulate the level of chronic inflammation and methods of screening for such agents. Also provided are compositions (e.g., aptamirs or exomirs) that facilitate cell / tissue-specific delivery of the miRNA agents.

The invention discloses a medicament for treating neovascularization diseases. The medicament employs miRNA-132 and miRNA-155 as targets and two specific antagomirs, antagomir-132 and antagomir-155, as the basic components. The above two micronucleus acids are knocked down in a lesion at the same time, so as to inhibit excessive proliferation of new vessels to achieve therapeutic effect. To ensure the effective application of the drug, the invention adopts in vivo delivery vectors, such as a histidine-lysine polypeptide polymer HKP and a ligand targeted delivery nanoparticle system RGD-PEG-HKP, in order to improve the specificity and efficiency of medicament delivered into angiogenesis sites (eye or tumor).

Methods are provided for treating fibrosis of a tissue, including fibrosis of the liver, using combinations of antagomirs and / or locked nucleic acids. Compositions therefor are also provided.

The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

The present invention relates to microRNAs (miRNAs) which are associated with cancer, particularly including hematologic malignancies, and particularly T-cell acute lymphoblastic leukemia (T-ALL), and to the assessment and modulation thereof in the treatment and management of cancer. The present invention is directed to methods and compositions for diagnosing and treating cancer, particularly T-ALL, by modulating miRNAs, and the use of miRNAs and antagonists thereof, particularly antagomirs, for predicting and assessing response to treatment, in assays for isolating and selecting antagists, and as compositions for the treatment and management of cancer. Methods and compositions are provided for treatment or alleviation of cancer, particularly T-ALL, with antagonists / antagomirs of miRNAs, particularly one or more of miR-19b, miR-20a, miR26, miR92, miR148 and miR223.

The invention discloses application of microRNA-210 inhibitor in preparing medicine treating inflammatory dermatosis. A large quantity of experiments prove that in-vitro inhibiting of expression of microRNA-210 can obviously improve the expression of a target gene STAT6 of microRNA-210, thus the formation of cell proliferation by cutin and secretion of chemokine CCL20 are inhibited, migration of chemotaxis T cells of chemokine CCL20 to the skin lesion parts is further inhibited, and meanwhile, differentiation of TH1 and TH17 can be inhibited. MicroRNA-210 knockout and injection of the microRNA-210 inhibitor (antagomiR-210 modified by cholesterol) given into the skin lesion specifically inhibits the expression of microRNA-210, which can both obviously inhibit mouse skin inflammation and improve T cell immune imbalance. A novel pathophysiology mechanism is provided for inflammatory dermatosis, and a new strategy capable of being used for preparing the medicine treating inflammatory dermatosis is provided.

The invention discloses an anti-aging stem cell culture medium and a culture method of mesenchymal stem cells. The anti-aging stem cell culture medium is prepared from a low-sugar alpha-MEM culture medium, fetal bovine serum, miR-705 antagomir, vitamin C, glutamine, penicillin and streptomycin. The anti-aging stem cell culture medium can delay the aging and functional decline of the mesenchymal stem cells caused by long-term in vitro passage and amplification.

The present application discloses roles for miR-93 in treating hypoxia and ischemia. Endothelial cells (HUVEC) and myocytes (C2C12) expressed miR-93 and up-regulated miR-93 in response to hypoxia and serum starvation. Over-expression of miR-93 in HUVECs promoted cell proliferation, prevented hypoxia-induced apoptosis, and enhanced endothelial cell tube formation. miR-93 knockdown in HUVECs resulted in increased hypoxia-induced apoptosis and decreased tube formation. Over-expression or knockdown of miR-93 in myocytes resulted in reduced or increased hypoxia-induced apoptosis, respectively. Down-regulation of miR-93 in C57BL / 6 mice with antagomiR resulted in attenuated perfusion recovery (% non-ischemic leg at day-21: Scramble 85.22.9 vs. AntagomiR-93 67.96). Over-expression of miR-93 in BALB / C mice improved perfusion recovery (% non-ischemic leg at day 21: PremiR-93 757.5 vs. Scramble 59.62.5). The present invention encompasses the use of miR-93 and regulation of miR-93 to treat and prevent hypoxia, ischemia, and other injuries, diseases, disorders, and conditions associated with ischemia.

The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

The inhibition of miRNA miR-33 is shown to promote the polarization of macrophages from an M1 to an M2 phenotype. MiR-33 inhibitors are therefore useful for treating inflammation in subjects. Endogenous microRNAs can be silenced using antagomirs. The miR-33 inhibitor is preferably an antagomir having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

The invention relates to the diagnostic and therapeutic uses of a miRNA molecule, an equivalent or a source thereof in a neuronal deficiency or a disease and condition associated with neuronal deficiency.

The invention discloses an anti-skin squamous cell carcinoma medicament, i.e., antagomir-365-2. The antagomir-365-2 is a chemically-modified antisense oligonucleotide of which the nucleotide sequence is shown as SEQIDNO:1 in which two continuous basic groups at a 5' end and four continuous basic groups at a 3' end are modified with thiophosphoric acid, the 3' tail end is marked with cholesterol, and all basic groups are modified through methylation. The anti-skin squamous cell carcinoma medicament, i.e., antagomir-365-2 disclosed by the invention can be enriched on a target cell by overcomingthe obstacles of cell membranes, tissues and the like, can directly enter cells cultured in vitro and in-vivo tumorigenesis tissues, is an ideal medicament for performing in-vitro and in-vivo skin squamous cell carcinoma treatment experiments, and can be used for effectively inhibiting invasion and transfer of tumor cells in vitro and effectively inhibiting growth of tumors and eliminating tumorsin vivo. The antagomir-365-2 disclosed by the invention has a remarkable resisting effect on skin squamous cell carcinoma, and is a target gene medicament for treating skin cancers.

The invention relates to negative functional modulators of erythropoietin (EPO) for use in the treatment of cancers, in the therapy of autoimmune -based and non-autoimmune based chronic inflammatory diseases, and in the treatment of patients under-going organ or tissue transplant, or for the treatment of hemophilic arthropathy, hemophilia A and B, von Willebrand disease, angiodysplasia, proliferative disorders and neurological diseases characterized in their pathogenesis by primary neuroinflammation and / or neuroinflammation secondary to other causes. Such modulators are anti-EPO antibodies and their derivatives: anti-EPO receptor antibodies (EPOR), antisense oligonucleotides, decoy DNA, decoy RNA, ribozyme, antagomir, shRNA, LNA and / or siRNAs that inhibit the expression of the gene encoding EPO or EPOR.

The invention belongs to the technical field of pharmacy, particularly relates to application of an miRNA inhibitor in the preparation of drugs for resisting Mycobacterium tuberculosis, and relates toa Mycobacterium-tuberculosis-resistant drug. A series of experiments prove that miR-27a antagomir can lower the intracellular survival of Mycobacterium tuberculosis after the Mycobacterium tuberculosis infects macrophage. Related animal experiment results show that the miR-27a antagomir can effectively relieve the pathological injury of the lung and can evidently lower the content of the Mycobacterium tuberculosis in the lung. The new application of the miRNA inhibitor miR-27a antagomir in the preparation of the drugs for resisting the Mycobacterium tuberculosis is provided, and the miR-27a antagomir can evidently effectively inhibit Mycobacterium tuberculosis infection, is capable of favorably providing effective drug support for the treatment of tuberculosis and is promising in clinicalapplication prospect.

The invention discloses the application of microRNA-26a in preparation of a drug for prevention or treatment of pulmonary fibrosis. According to the application of the microRNA-26a in preparation of the drug for prevention or treatment of the pulmonary fibrosis, experiments prove that microRNA-26a (miR-26a) expressions in experimental pulmonary fibrosis mice and clinical pulmonary fibrosis patients are substantially reduced; antagomiR-26a modified by cholesterol or LNA-AMO-26a modified by a locked nucleic acid (LNA) technology is used for specific inhibition of the miR-26a, and results show that mice pulmonary fibrosis can be caused; more importantly, the application further founds that: through use of the antagomiR-26a modified by the cholesterol or the LNA-miR-26a modified by the locked nucleic acid (LNA) technology for overexpression of the miR-26a in pulmonary tissues, the generation of the experimental pulmonary fibrosis can be effectively relieved; and the microRNA-26a modified by the cholesterol and the locked nucleic acid (LNA) are more safe relative to adenovirus transfection used in the experiments in the prior art. The application of the microRNA-26a in preparation of the drug for prevention or treatment of the pulmonary fibrosis provides a new pathophysiology mechanism for the generation of the pulmonary fibrosis, and provides the new drug for prevention and treatment of pulmonary fibrosis diseases.

The invention discloses the application of a miR-16 antagonist in the preparation of a drug for inhibiting non-alcoholic fatty liver disease. The sequence of the miR-16 is: AGCAGCAUUGUACAGGGCUAUGA. The inventors have proved through a large number of experiments that highly expressed miR-16 in cells is related to the occurrence of NAFLD, and inhibiting the level of miR-16 can significantly reduce the expression of pathologically related molecules in NAFLD model cells; miR-16 regulates the synthesis and decomposition of lipid metabolism in NAFLD cell models The expression of key enzymes in the pathway, inhibiting miRNA-16 can alleviate the pathological changes of fatty liver; and miR-16 Antagomir, as an inhibitor of microRNA-16, specifically inhibits the expression of microRNA-16, and can significantly inhibit NAFLD.

A chemotherapy drug-sensitizing method includes: transfecting antisense oligonucleotide (e.g., siRNA-1976 or antagomir-1976) to a cancer cell to form a transfected cancer cell for blocking miR-1976 of the cancer cell; providing a treatment of cancer drug (or anticancer drug combination) to the transfected cancer cell whose miR-1976 is blocked by the antisense oligonucleotide; the transfected cancer cell providing a degree of sensitivity for the cancer drug due to its miR-1976 being blocked.

The invention discloses an anti-skin squamous cell carcinoma medicament, i.e., antagomir-365-2. The antagomir-365-2 is a chemically-modified antisense oligonucleotide of which the nucleotide sequence is shown as SEQIDNO:1 in which two continuous basic groups at a 5' end and four continuous basic groups at a 3' end are modified with thiophosphoric acid, the 3' tail end is marked with cholesterol, and all basic groups are modified through methylation. The anti-skin squamous cell carcinoma medicament, i.e., antagomir-365-2 disclosed by the invention can be enriched on a target cell by overcomingthe obstacles of cell membranes, tissues and the like, can directly enter cells cultured in vitro and in-vivo tumorigenesis tissues, is an ideal medicament for performing in-vitro and in-vivo skin squamous cell carcinoma treatment experiments, and can be used for effectively inhibiting invasion and transfer of tumor cells in vitro and effectively inhibiting growth of tumors and eliminating tumorsin vivo. The antagomir-365-2 disclosed by the invention has a remarkable resisting effect on skin squamous cell carcinoma, and is a target gene medicament for treating skin cancers.

The invention relates to negative functional modulators of erythropoietin (EPO) for use in the treatment of cancers, in the therapy of autoimmune -based and non-autoimmune based chronic inflammatory diseases, and in the treatment of patients under-going organ or tissue transplant, or for the treatment of hemophilic arthropathy, hemophilia A and B, von Willebrand disease, angiodysplasia, proliferative disorders and neurological diseases characterized in their pathogenesis by primary neuroinflammation and / or neuroinflammation secondary to other causes. Such modulators are anti-EPO antibodies and their derivatives: anti-EPO receptor antibodies (EPOR), antisense oligonucleotides, decoy DNA, decoy RNA, ribozyme, antagomir, shRNA, LNA and / or siRNAs that inhibit the expression of the gene encoding EPO or EPOR.

The invention relates to a miRNA molecule which is of a double chain structure. The miRNA molecule comprises a positive-sense strand and a negative-sense strand, wherein the nucleotide sequence of the positive-sense strand is as shown in SEQ ID NO: 1 in a sequence table, and the nucleotide sequence of the negative-sense strand is as shown in SEQ ID NO: 2 in a sequence table; or the miRNA molecule is of a single-strand structure, the nucleotide sequence of which is as shown in SEQ ID NO: 3. The designed and synthesized miRNA avi-miR-316 agomir and miRNA avi-miR-316 antagomir can make aphids fatal, thereby providing a novel effective product for prevention and control of aphids. A target gene acted thereby can be used as an ideal candidate gene resource for creating a novel anti-aphid crop medicated by RNAi, thereby providing a novel research concept for pest control. The miRNA molecule has very high research value and a wide application prospect.

The invention relates to the diagnostic and therapeutic uses of a miRNA molecule, an equivalent or a source thereof in a neuronal deficiency or a disease and condition associated with neuronal deficiency.

The invention relates to negative functional modulators of erythropoietin (EPO) for use in the treatment of cancers, in the therapy of autoimmune-based and non-autoimmune based chronic inflammatory diseases, and in the treatment of patients undergoing organ or tissue transplant, or for the treatment of hemophilic arthropathy, hemophilia A and B, von Willebrand disease, angiodysplasia, proliferative disorders and neurological diseases characterized in their pathogenesis by primary neuroinflammation and / or neuroinflammation secondary to other causes. Such modulators are anti-EPO antibodies and their derivatives: anti-EPO receptor antibodies (EPOR), antisense oligonucleotides, decoy DNA, decoy RNA, ribozyme, antagomir, shRNA, LNA and / or siRNAs that inhibit the expression of the gene encoding EPO or EPOR.

The present invention relates to microRNAs (miRNAs) which are associated with cancer, particularly including hematologic malignancies, and particularly T-cell acute lymphoblastic leukemia (T-ALL), and to the assessment and modulation thereof in the treatment and management of cancer. The present invention is directed to methods and compositions for diagnosing and treating cancer, particularly T-ALL, by modulating miRNAs, and the use of miRNAs and antagonists thereof, particularly antagomirs, for predicting and assessing response to treatment, in assays for isolating and selecting antagonists, and as compositions for the treatment and management of cancer. Methods and compositions are provided for treatment or alleviation of cancer, particularly T-ALL, with antagonists / antagomirs of miRNAs, particularly one or more of miR-19b, miR-20a, miR26, miR92, miR148 and miR223.

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. In particular, hepatocellular carcinoma (HCC) has become the most common primary hepatic malignancy. Current therapies are now satisfying and there is therefore an important need for identifying new therapeutic avenues. IL-27 is a cytokine produced in liver microenvironment but its role in the pathogenesis of HCC has never been investigated. The inventors now show that IL-27 exerts anti-proliferative activities in HCC cell lines. However, the inventors show that in patients suffering from HCC that a decreased expression of WSX-1 (i.e. the IL-27 receptor) is associated with a worse prognosis and contributes to the tumor proliferation. The inventors then identified some microRNAs (miR) that are capable of repressing the expression of WSX-1 and show that overexpression of said miR are associated with a worse prognosis in patients. Finally, the inventors demonstrate that antagomirs restore the expression of WSX-1 that can thus restore the tumor cell sensitization to IL-27 properties. Accordingly, the present invention relates to methods for the treatment and prognosis of cancer, in particular hepatocellular carcinoma (HCC).

The inhibition of miRNA miR-33 is shown to promote the polarization of macrophages from an M1 to an M2 phenotype. MiR-33 inhibitors are therefore useful for treating inflammation in subjects. Endogenous microRNAs can be silenced using antagomirs. The miR-33 inhibitor is preferably an antagomir having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

The invention relates to a miRNA molecule. The miRNA molecule is of a two-strand structure containing a sense strand and an antisense strand, wherein the nucleotide sequence of the sense strand is shown as SEQ ID NO: 1 in a sequence table, and the nucleotide sequence of the antisense strand is shown as SEQ ID NO: 2 in the sequence table; or the miRNA molecule is of a single-strand structure of which the nucleotide sequence is shown as SEQ ID NO: 3 in the sequence table. According to the artificially designed and synthesized miRNA avi-miR-184-3p agomir and miRNA avi-miR-184-3p antagomir have lethality for aphid, a novel effective product is provided to prevent and control aphid; the target gene under the action of the product can be used as an ideal candidate gene resource for developing RNAi-mediated novel pest resisting crops. Therefore, a novel research ideal on pest prevention and control is provided; the miRNA molecule is high in research value and has a good application prospect.

The invention provides a method for enhancing and carrying out suppression expression on miRNA in the embryogenic callus of longan. An miRNA mimic agomir and efficient blocker antagomir, which undergo chemical modification and special mark design according to mature miRNA, are guided into the embryogenic callus cells of longan by adopting a cell transfection agent Lipofectamine 2000 reagent, thus achieving specific enhancement or suppression of the activity of target miRNA in the longan living body, and meanwhile, miRNA expression system optimization and effect duration identification are carried out. The method has the advantages of simplicity and rapidness in operation, obvious interference effects, stability, durability, and the like, avoids the defects that depending on the transgenic technology, existing methods are long in experimental periods and waste time and energy, provides an efficient and convenient method for research of miRNA in the callus of longan and has important significance to miRNA expression regulation and function identification.

The invention discloses a culture medium for culturing mesenchymal stem cells. The culture medium is prepared from the following component raw materials: 5 to 50 [mu] l / ml of serum, 8 to 16 ng / mL of miR-705antagomir, 30 to 60 mg / L of ascorbic acid, 2 to 5 ng / mL of honeysuckle flower powder, 15 to 30 [mu] g / mL of luteolin, 8 to 20 ng / mL of epidermal growth factors, 40 to 60 U / mL of penicillin, 70 to 80 [mu] g / mL of streptomycin, 25 to 100 [mu] g / mL of vitamin C and a cell basal culture medium. The invention further discloses a culture method for culturing the mesenchymal stem cells. The culture method comprises the following steps: step 1, preparing an incubator; step 2, obtaining bone marrow mesenchymal stem cells; and step 3, culturing the bone marrow mesenchymal stem cells. Aiming at microRNA abnormal expression in the aging process of the mesenchymal stem cells, a specific microRNA inhibitor antagomir is adopted, a transfection reagent and a carrier are not needed, and the microRNA inhibitor antagomir directly enters the cells, so that cell expression is safely and efficiently regulated, miR-705 is reduced, the aging and function reduction of the mesenchymal stem cells caused by long-term in-vitro passage amplification are delayed, and a foundation is established for clinical application of the BMSC.