313 results about "Antisense oligonucleotides" patented technology

The present invention relates to an oligonucleotide comprising from 10 to 25 nucleotides wherein at least one of said nucleotides is modified, and the oligonucleotide hybridizes with the pre-mRNA of the neurociliin 1 (NRP1, CD304) of SEQ ID NO. 366 (GRCh38p13Chr 1033177492-33336262-1) or with the mRNA of the NRP1 of SEQ ID NO. 367 (RefSeq ID NM003873.6). The invention also relates to a pharmaceutical composition comprising the oligonucleotide. The pharmaceutical composition and the oligonucleotide are for use in a method of preventing and / or treating cancer, ophthalmic disease, autoimmune disorder and / or immune disorder.

The invention discloses application of a tea tree CsGT-3b gene in improving the disease resistance of plants and a method of the tea tree CsGT-3b gene. The CsGT-3b gene is a Trihelx transcription factor family gene, the CsGT-3b gene is constructed to a plant expression vector and is transferred into tobacco, a transgenic tobacco plant is obtained through stable genetic transformation, and the CsGT-3b gene shows relatively strong fungal inhibitory activity on botrytis cinerea inoculation; according to the present invention, the CsGT-3b gene on the tea tree leaf is subjected to instantaneous silencing by using the antisense oligonucleotides (AsODNs) technology, such that the disease resistance of the plant on the lasiodiplodia theobroma is significantly weakened, and the CsGT-3b gene on the tea tree leaf is subjected to the enzyme-linked immunosorbent assay so as to significantly reduce the disease resistance of the plant on the lasiodiplodia theobroma; therefore, the CsGT-3b gene has the effect of improving the disease resistance of the plants, can be used as a disease-resistant gene, can improve the disease resistance of the plants by being introduced into the plants such as tobacco, tea trees or vegetables, and has a wide market application prospect.

The invention discloses antisense oligonucleotides for reducing XDH gene expression in a targeted manner and application of the antisense oligonucleotides, and belongs to the technical field of biological medicines. The antisense oligonucleotide mediates the degradation of the target mRNA through an RNase H (RNase H) dependent cleavage mechanism, and the mRNA expression of the XDH gene is horizontally knocked down after transcription; the antisense oligonucleotide molecule has a specific nucleic acid sequence, is combined with chemical modification design, can specifically bind XDH mRNA molecules in a targeting manner, promote XDH mRNA degradation and inhibit XDH protein synthesis, so that the expression level of XDH in cells is reduced, uric acid synthesis is reduced, the purpose of reducing uric acid is finally achieved, and cell experiments and animal model tests show that the antisense oligonucleotide molecule has a good application prospect. The antisense oligonucleotide molecule disclosed by the invention has a good uric acid reducing effect, and is long in drug effect duration and high in drug safety.

The application discloses a drug-loaded micelle capable of effectively crossing the blood-brain barrier, which is an amphiphilic conjugate composed of a reduction-sensitive paclitaxel prodrug and a nucleic acid complex, wherein the reduction-sensitive paclitaxel prodrug is used as a hydrophobic part, and the nucleic acid complex is used as a hydrophilic part, and the drug-loaded micelle is self-assembled in an aqueous environment; the reduction-sensitive paclitaxel prodrug is formed by the reaction of paclitaxel and a disulfide bond-containing linker; and the nucleic acid complex is formed by connecting an antisense oligonucleotide and an interfering RNA through a DNA bridge. The drug-loaded micelle exhibits superior blood-brain barrier penetration, effectively realizes enrichment in brain tumors, solves the problem of low blood-brain barrier penetration efficiency of existing nano-carriers, and provides an effective basis for brain drug delivery and brain diseases such as brain tumor imaging and treatment.

The present invention relates to a recombinant antisense oligonucleotide that targets CD33 mRNA and to a method of preparing a substantially pure population of edited eukaryotic cells comprising the steps of i) editing a population of eukaryotic cells by the use of base editors, (ii) treating the same population with antisense oligonucleotides according to the invention to transiently downregulate CD33 and iii) enriching the population of edited eukaryotic cells that is negative for CD33.

Antisense oligonucleotides for modulating UNC13A splicing (e.g., inhibiting the inclusion of UNC13A hidden exons in mature UNC13A mRNA), compositions comprising such antisense oligonucleotides, and methods of use are described. Also disclosed are pharmaceutical compositions comprising one or more antisense oligonucleotides, and methods for treating UNC13A-related diseases or diseases associated with TDP-43 dysfunction in a subject by administering the antisense oligonucleotides to that subject.

The present invention relates to agents, compositions, and methods for treating or ameliorating symptoms of cancer. Exemplary synergistic therapies include the use of antisense oligonucleotide agents to suppress expression of TGF-β2, alone and in combination with interferon-gamma. One or more biomarkers can be used to select subjects for treatment.

The present invention relates to the field of therapy and drug delivery. More specifically, therapeutic methods and pharmaceutical compositions for treating disorders of blood-tissue barrier-protected organs that harbor substantial populations of postmittal neurons, such as organs derived from the neural tube, including the central nervous system and the eye. The disclosed methods and compositions involve topical administration of an effector component that targets intracellular biological targets to such organs, in combination with a saponin component that enhances the effective uptake of the effector component into cells and / or enhances the effective delivery of the effector component within cells where the biological target is present. For example, the effector component may be an oligonucleotide therapeutic that targets gene products associated with CNS and / or ocular disorders. Due to the cellular uptake stimulating and / or endosomal escape enhancing effects of the saponin component, the neuropharmaceuticals and ophthalmic compositions presented herein for topical administration to the CNS and / or eye, respectively, can be formulated with lower concentrations of the effector component and / or lower volumes, which provides safety benefits to neurons and patient comfort.

Modified multi-segment antisense oligonucleotides and methods for reducing expression of target mRNA, DNA, and proteins are provided. Such methods, oligonucleotides, and compositions may be used to treat, prevent, or ameliorate a disease or disorder.

The invention provides antisense oligonucleotide aiming at a Sptbnl target spot and application of the antisense oligonucleotide. The antisense oligonucleotide can be used for knocking down the expression of Sptbnl, and in-vivo and in-vitro experiments find that the antisense oligonucleotide can be used for treating hyperlipidemia and NASH and can also be used for treating neovascular eye diseases.

The invention relates to a group of antisense oligonucleotides for specifically inhibiting an androgen receptor and application thereof, the length of the antisense oligonucleotides is 14-22 basic groups, and the antisense oligonucleotides (ASO) are applied as follows: (1) preparing a preparation for inhibiting the expression quantity of AR protein; (2) preparing a medicine or a medicine composition for treating androgen-induced alopecia; or (3) preparing a medicine or a medicine composition for treating androgen-induced acne; or (4) inhibiting expression or activation of AR protein; and (5) treating diseases caused by overexpression or transition activation of the AR protein, wherein the diseases comprise but are not limited to tumors, alopecia or acne caused by overexpression or transition activation of the AR protein.

The application provides an antisense oligonucleotide Jag-i9 ASO and application thereof, relates to the technical field of biological medicine, and the antisense oligonucleotide Jag-i9 ASO has the sequence of 5'-ACTGGGCCCTGCACCTGA-3'. By providing the antisense oligonucleotide of a specific sequence, the binding site of target heterogeneous ribonucleoprotein K and the Jag2 gene is targeted, the expression of the pro-inflammatory Jag2 subtype is inhibited, the Jag2 gene splicing site can be accurately targeted, the heterogeneous ribonucleoprotein K binding function is specifically blocked, a targeted intervention means is provided for the treatment of myocardial ischemia-reperfusion injury, the generation of the pro-inflammatory subtype is inhibited by efficiently and accurately regulating the alternative splicing of a specific gene, myocardial cell apoptosis and inflammatory response are reduced, myocardial function is improved, and a new approach is provided for the prevention and treatment of myocardial ischemia-reperfusion injury, the treatment effect is improved, and the advantages of reducing side effects are achieved.

The invention discloses application of coronavirus SL5 as a target spot in preparation of a medicine for preventing and treating coronavirus infection. The drug target coronavirus SL5 is a No.5 stem loop of a 5 'UTR region of the coronavirus and participates in regulation and control of virus mRNA translation. The invention further discloses seven inhibitors capable of infecting human coronavirus SL5, namely the antisense oligonucleotides specifically targeting SL5 are used for inhibiting coronavirus infection. Experiments prove that the translation level of coronavirus mRNA can be remarkably inhibited by applying the antisense oligonucleotide specifically targeting the coronavirus SL5 in vitro. The coronavirus SL5 provided by the invention can be used as a drug target for screening candidate drugs for inhibiting the translation of coronavirus mRNA, and is of great significance to the development, prevention and treatment of anti-coronavirus drugs in the future.

Provided herein are compositions and methods for modulating MMP9 expression. In some instances, compositions and methods are used to treat a neurodegenerative disorder. In some instances, the compositions comprise antisense oligonucleotides.

This invention provides targeted conjugates and methods that improve the targeting and local in vivo delivery of oligonucleotides. [Solution] A composition containing a targeted oligonucleotide-HES conjugate is provided as a method for constructing and using the conjugate in therapeutic, diagnostic, and other applications. The oligonucleotide-HES complex contained in the targeted oligonucleotide-HES conjugate can cross membranes in a receptor-independent manner and can deliver oligonucleotides containing complementary sequences to the cytosol of living cells in vivo. The targeted oligonucleotide-HES conjugate has uses including the targeting and / or local delivery of antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs, and other nucleic acid sequences in living organisms.

An antisense oligonucleotide and the use thereof. A series of ASOs are designed on the basis of the genome sequence of a hepatitis B virus (HBV), and are modified by means of using a specific modification mode. Cell and animal experiment results show that some modified ASOs obtained by means of using the specific modification mode can significantly reduce the expression of one or more HBV genes and block the life cycle of viruses, and therefore can be used to develop drugs for treating HBV infection-related diseases.

The present invention provides: a compound which is an antisense oligonucleotide capable of regulating the expression of a RasGRP4 gene and treating myositis and rheumatoid arthritis, and which has a nucleic acid base sequence consisting of 8-80 linked nucleosides and comprising at least 8 consecutive nucleic acid bases complementary to a transcript of RasGRP4; or a pharmacologically acceptable salt thereof.

The present invention relates to an antisense oligonucleotide targeting an interleukin 4 receptor and the use thereof. The antisense oligonucleotide (ASO) molecule has a length of 16-22 bases and is specifically paired with a specific region of a target gene (interleukin 4 receptor). The ASO is used for treating diseases associated with IL-4Rα, which includes, but is not limited to, asthma (including eosinophilic asthma), atopic dermatitis, eosinophilic esophagitis, sinusitis, nasal polyps, prurigo nodularis, urticaria, chronic obstructive pulmonary disease, bullous pemphigoid, pruritus, and gastritis.

Antisense oligonucleotides are provided which target potassium channel tetramerization domain containing 20 (KCTD20) and can be used in treating, inhibiting, or reducing the severity of a neurodegenerative disease, especially those involving glutamate excitotoxicity.

A method for regulating the mRNA and protein expression of an SCN1A gene, and a compound. Provided is a use of an antisense oligonucleotide guide RNA in the preparation of a drug for altering the expression of a target protein in a cell of a subject. The cell has a pre-mRNA encoding the target protein, wherein the pre-mRNA comprises an intron, an exon flanking a 5' splice site of the intron, and an exon flanking a 3' splice site or pseudo 3' splice site of the intron; the antisense oligonucleotide guide RNA can bind to the pre-mRNA to form a structure capable of recruiting ADAR in a cell, thereby forming a complex containing an ADAR protein; and the target protein is an Nav1.1 protein. That is, the function or expression of the functional RNA and target protein of a target gene is affected by regulating the alternative splicing of the pre-mRNA of the target gene, thereby achieving the objective of treating diseases.

Provided are compositions comprising an oligonucleotide that targets Angiopoietin-like 4 (ANGPTL4). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating a metabolic or cardiovascular disorder by providing an oligonucleotide that targets ANGPTL4 to a subject in need thereof.

Provided herein are methods for treating or preventing pouch inflammation comprising administering a SMAD7 antisense oligonucleotide or a pharmaceutical formulation comprising the SMAD7 antisense oligonucleotide.

An isolated or purified antisense oligomer for modifying pre-mRNA splicing in the CNOT3 gene transcript or part thereof.

The present invention relates to a new therapeutic approach for treatment of ANCA-associated vasculitis (Anti-neutrophil cytoplasmic autoantibody-associated vasculitis, AAV). It provides an agent for reducing expression of proteinase 3 (PR3) in a cell, in particular, a gene editing compound targeting the proteinase 3 gene, an epigenetic editing compound targeting the proteinase 3 gene, or an expression vector encoding an inhibitory oligonucleotide capable of selectively binding to a target nucleic acid sequence in mRNA encoding proteinase 3, e.g., an inhibitory oligonucleotide capable of inducing RNAi or an antisense oligonucleotide. Further, a method of reducing expression of proteinase 3 in a hematopoietic stem cell or cell derived therefrom, e.g., a neutrophil, is provided, as well as such cells having a reduced expression of proteinase 3. The cells or agents can be used for treating a subject having a proteinase 3-ANCA-associated vasculitis.

Disclosed herein are pharmaceutical formulations comprising antisense oligonucleotides, or salts thereof, that reduce expression of CAPN2, which encodes calpain-2.

The present invention relates to an antisense oligonucleotide (oligomer) complementary to NAT8L (N-acetyltransferase 8-like) precursor mRNA, which is capable of inhibiting the expression of NAT8L in a cell that expresses NAT8L. Inhibition of the expression of NAT8L is beneficial to the treatment of Canadian disease (Canadian disease).

Disclosed herein is a composition comprising an oligonucleotide targeting MST1. The oligonucleotide may comprise a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein is a method for treating a condition associated with an MST1 mutant, comprising providing a subject with an oligonucleotide targeting MST1.

The present application relates to the technical field of biological medicine engineering, and provides application of RBFOX2 inhibitor in treatment of inflammatory bowel disease, and particularly relates to the role of interfering RNA or antisense oligonucleotide or recombinant expression vector targeting RBFOX2 coding sequence in preparation of products for treating colitis and its related symptoms and / or other complications, and also relates to corresponding recombinant vectors or pharmaceutical compositions. The RBFOX2 inhibitor can effectively reduce the level of proinflammatory cytokines, inhibit the activation of macrophages, has effective application value in relieving and treating colonic inflammation and other symptoms and / or other complications of inflammatory bowel disease, provides a new target for treatment of inflammatory bowel disease, and has wide clinical application prospect.

Disclosed are use of the Camellia sinensis (L.) O. Kuntz CsMYB1 gene in improving disease resistance of a plant and a method for improving disease resistance of a plant. The CsMYB1 gene is a transcription factor gene of the MYB family. CsMYB1 is constructed into a plant expression vector, and the vector is transferred into Nicotiana benthamiana. A transgenic tobacco plant is obtained by means of stable genetic transformation, and the plant exhibits relatively strong fungal inhibitory activity against inoculated Botrytis cinerea hyphae. Transient silencing of the CsMYB1 gene of Camellia sinensis (L.) O. Kuntz leaves using a technology of antisense oligonucleotides (AsODNs) significantly reduces the disease resistance of the plant. Therefore, the CsMYB1 gene has the effect of improving the disease resistance of a plant and can be used as a disease-resistant gene. Introducing the gene into plants such as tobacco, Camellia sinensis (L.) O. Kuntz, or vegetables can improve the disease resistance of these plants. The present invention has broad market application prospects.

This disclosure relates to reagents such as antisense oligonucleotides that bind to nucleic acids encoding cryptic exons, thereby inhibiting or preventing ELAVL3 cryptic splicing, and to their use in the treatment or prevention of TDP-43-related neurodegenerative or neurological diseases or conditions associated therewith. In some embodiments, the antisense oligonucleotide is a nucleobase polymer capable of reducing the level or expression of intracellular ELAVL3 cryptic exon RNA and increasing or restoring the expression of functional ELAVL3 protein without substantially incorporating the cryptic exon RNA peptide sequence.