521 results about "Antisense oligonucleotides" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The present disclosure, in some aspects, relates to antisense oligonucleotides (ASO) for use in the prevention or treatment of a disease or a condition associated with low- density lipoprotein (LDL) in a subject. In some embodiments, the ASO effects site-directed adenosine-to-inosine (A-to-l) editing of a target adenosine in a target RNA sequence derived from a sequence of an endogenous low-density lipoprotein receptor (LDLR) gene such that: a) the modified LDLR protein has: (i) reduced binding to the inducible degrader of the LDLR protein (IDOL); (ii) increased stability; (iii) improved resistance to IDOL-mediated degradation; (iv) increased LDLR protein expression; and / or (v) increased activity or function to take up LDL; and / or b) editing of the 3'-untranslated region (UTR) of the target RNA leads to an increase in LDLR protein expression and / or stability.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The present invention relates to antisense oligonucleotides (AONs) that can mediate RNA editing by binding to a target RNA nucleic acid molecule, preferably an RNA transcript molecule, in a cell and recruiting an endogenous deaminating enzyme in the cell to deaminate a target adenosine in the target RNA molecule to an inosine. The target RNA molecule is a transcript molecule form the SLC10A1 gene that encodes the Na+ / Taurocholate Co-transporting Polypeptide (NTCP), and the target adenosine is the adenosine in the GAC codon coding for aspartic acid (D) at position 24 of the NTCP protein. The deamination of the adenosine changes the amino acid to a glycine (G). The RNA editing of the adenosine will result in a loss-of-function of the NTCP protein, which will result in lowered uptake of bile acids from the portal circulation into the liver, thereby lowering the risk of suffering from disorders related to bile accumulation in the liver.

Antisense oligonucleotides for splicing modulation of UNC13A (e.g., inhibiting inclusion of an UNC13A cryptic exon into an UNC13A mature mRNA), compositions including the antisense oligonucleotides, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more antisense oligonucleotides and methods of treating an UNC13A-associated disease or a disease associated with TDP-43 dysfunction in a subject by administering the antisense oligonucleotides to the subject.

Provided herein are methods, compositions, and kits for treating an HBV infection comprising administering to a subject an siRNA specific for an HBV target and an antisense oligonucleotide specific for an HBV target. The methods, compositions, and kits provided herein reduce HBV DNA, HBV mRNA, and HBV protein levels in the subject.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Methods featuring phosphoryl guanidinium based backbone and morpholino with phosphoramidite chemistry result in neutral antisense oligonucleotides. The PGMO is composed of a morpholino backbone linked to a phosphoryl guanidinium internucleotide (PG) linkage. These oligonucleotides can be used to treat cancer, autoimmune diseases, and other rare diseases.

Antisense oligonucleotides for splicing modulation of UNC13A (e.g., inhibiting inclusion of an UNC13A cryptic exon into an UNC13A mature mRNA), compositions including the antisense oligonucleotides, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more antisense oligonucleotides and methods of treating an UNC13A-associated disease or a disease associated with TDP-43 dysfunction in a subject by administering the antisense oligonucleotides to the subject.

The invention discloses application of a Cslnc924 gene in diagnosis or prevention and treatment of tea tree anthracnose, and relates to the technical field of prevention and treatment of tea tree anthracnose. The Cslnc924 gene is used for promoting the expression of the Cslnc924 gene so as to enhance the resistance of tea trees to colletotrichum gloeosporioides, and the cDNA full-length sequence of the Cslnc924 gene is as shown in SEQ ID No.1. The method has the beneficial effects that on the basis of an agrobacterium tumefaciens-mediated transient overexpression technology and an antisense oligonucleotide-mediated gene silencing technology, the Cslnc924 gene is overexpressed and silenced on tea tree leaves respectively, and an anthrax inoculation test is carried out. Results show that when Cslnc924 is overexpressed, compared with a control group, CsmiR390 is remarkably up-regulated, downstream CsARFs (CsARF2.1, CsARF2.2, CsARF3 and CsARF4.1) of CsmiR390 are remarkably down-regulated, at the moment, resistance of tea trees to colletotrichum gloeosporioides is enhanced, and the area of disease spots is remarkably reduced.

Exemplary olfactory delivery scaffolds may include 1) an olfactory targeting component, stimulant, or odorant that is recognized by the olfactory nerves via, for example, a smell response, 2) a molecule with biological activity, a therapeutic component, and / or drug (sometimes collectively referred to herein as a “therapeutic component”), and 3) a linker component that links the olfactory targeting component and therapeutic component together. The olfactory delivery scaffolds may be used to deliver a molecule with biological activity and / or a therapeutic component to a subject's neurological system through the olfactory pathway and pharmaceutical compositions useful in the treatment of neurological and / or neurodegenerative diseases.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

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.

Disclosed herein are double stranded ribonucleic acids (dsRNAs) and synthetic antisense oligonucleotides (ASOs) for use in inhibiting the expression of MUC5B and in the treatment of a subject having a disease or disorder characterized by overexpression of MUC5B, including in subjects having lung disease or in a subject at risk of developing lung disease, for example, in a subject having or at risk of developing idiopathic pulmonary fibrosis.

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 invention relates to chemically modified oligonucleotides comprising a sequence with a length of 23 to 80 nucleotides, capable of binding to a target sequence in a target RNA, comprising a central base triplet (CBT) of 3 nucleotides (5′—N−1eN0fN+1g-3′) with the central nucleotide (N0) directly opposite to the target adenosine in the target RNA, wherein the core oligonucleotide comprises the following sequence: 5′—N−5aN−4b N−3cN−2dN−1eN0fN+1gN+2h N+3 iN+4j-3′ comprising different 2′ sugar and linkage modifications. The present disclosure also provides oligonucleotides and compositions thereof for use in use in the treatment or prevention of a genetic disorder, condition, or disease. Also provided are methods for editing a target adenosine or deaminating at least one specific adenosine in a target nucleic acid.

To provide exon-skipping oligomer conjugates for muscular dystrophy.SOLUTION: Disclosed is an antisense oligomer conjugate that is complementary to a selected target site of the human dystrophin gene and induces exon 45 skipping. The disclosure relates to a novel antisense oligomer conjugate suitable for exon 45 skipping of the human dystrophin gene and a pharmaceutical composition thereof. The disclosure also provides a method for inducing exon 45 skipping using the novel antisense oligomer conjugate, a method for enabling a subject having a mutation of the dystrophin gene that is amenable to exon 45 skipping to produce dystrophin, and a method for treating a subject having a mutation of the dystrophin gene amenable to exon 45 skipping.SELECTED DRAWING: None

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.

The present application relates to an agRNA (antisense oligonucleotide guide RNA, Antisense Oligonucleotide guide RNA) for editing RNA, which is characterized in that one agRNA molecule can bind to a plurality of non-continuous target regions of the target RNA. The invention also provides a composition containing the agRNA, a method for editing RNA, and application of the agRNA and the composition.

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.

Provided herein are MAPT antisense oligonucleotides and compositions comprising a MAPT antisense oligonucleotide. Also provided herein are methods of using the MAPT antisense oligonucleotides or compositions comprising a MAPT antisense oligonucleotide for reducing MAPT expression and / or treating tauopathy in a subject.