1408 results about "Oligonucleotide" patented technology

Provided herein are methods of determining a location or presence of a target analyte in a biological sample by detecting oligonucleotide-conjugated binding agents.

Methods for determining a location of a feature in a spatial array with features include: (a) providing an array with a first set of one or more features immobilized on a substrate, a first feature of the first set having a first barcoded oligonucleotide with a first spatial barcode and a first constant sequence, and a second set of one or more features immobilized on the substrate, a second feature of the second set having a second barcoded oligonucleotide with a second spatial barcode and a second constant sequence; (b) attaching the first constant sequence to the second constant sequence to generate a nucleic acid product; (c) determining all or a portion of a sequence of the nucleic acid product or a complement thereof; and (d) associating the second barcoded oligonucleotide with the first barcoded oligonucleotide in the nucleic acid product.

The technology described herein relates to 5'-modified nucleosides, nucleotides, oligonucleotides and double-stranded RNAs, e.g., siRNAs, and kits comprising them and methods of their use for inhibiting target genes.

Aspects of the disclosure relate to methods of reducing expression or activity of DUX4 (e.g., DUX4 protein and / or mRNA) and / or methods of treating facioscapulohumeral muscular dystrophy (FSHD) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention discloses a lipid compound capable of being used for gene delivery, a preparation method of the lipid compound and application of the lipid compound in gene delivery. Also disclosed herein is a lipid nanoparticle comprising the lipid compound, a gene delivery composition comprising the lipid compound or the lipid nanoparticle. The lipid compounds, lipid nanoparticles and delivery systems herein enable efficient complexation, protection, intracellular and targeted delivery and release of biomolecules, such as oligonucleotides and nucleic acids, in vitro and in vivo tissues and organs.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The present disclosure provides systems and methods for separating and characterizing oligonucleotides. Fixed dose combinations of small interfering RNAs can be subjected to denaturing ion pairing reverse phase liquid chromatography using optimal conditions to separate single RNA strands for purity analysis.

The present disclosure relates to cellular compositions that are modified to introduce a nucleic acid or vector expressing the same. Such compositions may be used to deliver nucleic acid to a target cell and treat disease such as cancer.

The invention provides a nucleic acid aptamer and a screening method thereof, the aptamer is of an oligonucleotide DNA structure, the nucleotide sequence of the nucleic acid aptamer is the nucleotide sequence of any DNA fragment as shown in SEQ ID NO: 1-9, and the nucleic acid aptamer can specifically target cardiac muscle cells (CMs). According to the invention, a new strategy can be provided for clinical treatment of cardiovascular diseases, and meanwhile, bioactive molecules such as microRNA (miRNA), small interfering RNA (small interfering RNA, siRNA), lipidosome, microspheres, microcapsules and the like can be carried to be used as an intracellular drug delivery tool.

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

Methods for determining a location of a feature on a spatial array include (a) providing an array of features on a substrate, where a feature of the array includes a barcoded oligonucleotide having, in a 5′ to 3′ direction, a spatial barcode, a cleavage domain, and a constant sequence; (b) hybridizing a priming oligonucleotide to the constant sequence; (c) extending the priming oligonucleotide using the barcoded oligonucleotide as a template; and (d) determining all or a portion of a sequence of the extended priming oligonucleotide corresponding to the spatial barcode, or a complement thereof, and a location of the extended priming oligonucleotide, and using the location of the extended priming oligonucleotide to determine the location of the feature on the spatial array.

The present disclosure describes novel reagents and processes for preparing oligonucleotides, which have two or more nucleotides. In one embodiment, the reagent is represented by Formula I. wherein: W is O or NH; R1 is -H or a solid support; R2 is a silyl hydroxyl protecting group or an alloc protecting group, R3 is a nucleoside or a group represented by (II) wherein (III) represents the point of attachment for R3.

Disclosed are, inter alia, therapeutic oligonucleotides for use in silencing a target gene in a cell or in a subject.

Compositions, methods and systems for targeted delivery using one or more shuttles operably linked to one or more cargos (e.g., cargo polypeptides, e.g., cargo oligonucleotides) and subsequent quantification of an abundance of one or more cargos (e.g, proteins) in a mixture (e.g., a complex mixture (e.g., in vivo)) or in a specific cell, tissue, or organ of interest (e.g., in vivo) using barcodes (e.g., peptide barcodes), binders (e.g., polypeptide binders), and binding agents (e.g., phage) are provided herein.

The present disclosure provides double stranded oligonucleotides, compositions, and methods relating thereto. The present disclosure encompasses the recognition that structural elements of double stranded oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and / or internucleotidic linkages) or patterns thereof, and / or stereochemistry (e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages), and / or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, Ago2 loading, thermal stability, in vivo stability, delivery to tissues and into cells, etc. The present disclosure also provides methods for treatment of diseases, e.g., hepatic diseases, central nervous system (CNS) diseases, etc., using provided double stranded oligonucleotide compositions, for example, in RNA interference.

The present disclosure provides siRNAs, modifiers, conjugates and uses thereof for targeted regulation of Factor 11 of coagulation (FXI) gene expression. A series of siRNAs are designed based on an FXI messenger ribonucleic acid (mRNA) sequence, alternate modification is carried out, and modification is carried out by utilizing a group of specific modification templates. Cellular and animal experiment results show that some alternately modified and specific template modified oligonucleotide sequences can significantly inhibit the expression of the FXI gene, and can be used for developing anticoagulant drugs.

Provided is a dual-target nucleic acid molecule for inhibiting the expression of the vegfa gene and ang-2 gene. A linker contains 2-10 nucleotides or abasic nucleotides, and is used for linking two independent oligonucleotides. One or more nucleotides or abasic nucleotides in the linker contain a lipophilic moiety, and the lipophilic moiety is a C12-26 saturated or unsaturated hydrocarbon chain. Compared to a situation where a specific lipophilic modification is located inside the two linked moieties of a dual-nucleic acid molecule structure, the nucleic acid molecule exhibits better efficacy and a longer-lasting therapeutic effect when the specific lipophilic modification is located on the linker.

The present disclosure provides a modified oligonucleotide sequence and its application. A series of siRNAs are designed based on the angiotensinogen (AGT) messenger ribonucleic acid (mRNA) sequence, and are alternately modified and modified using a specific set of modification templates. The results of cell and animal experiments show that some alternately modified and specifically template-modified oligonucleotide sequences can significantly inhibit the expression of the AGT gene, and can be used for developing drugs for treating related diseases such as hypertension.

The invention relates to a structure, synthesis and application of morpholine ring oligonucleotide. A morpholine ring oligonucleotide structure is named Mo-CEBPA, can induce intracellular redox imbalance and trigger ferroptosis by inhibiting expression of CEBPA in hepatoma carcinoma cells, can assist sorafenib in killing hepatoma carcinoma cells, and overcomes the defect that existing drugs cannot efficiently induce hepatoma carcinoma cell ferroptosis.

The invention relates to a novel three-antigen HSV-2 subunit vaccine as well as a preparation method and application thereof, and belongs to the technical field of biology. The novel three-antigen HSV-2 subunit vaccine comprises antigens and a composite adjuvant, the antigens comprise HSV-2 gB2 envelope glycoprotein, HSV-2 gC2 envelope glycoprotein and HSV-2 gD2 envelope glycoprotein, and the composite adjuvant is CpG oligonucleotide and an aluminum adjuvant; the vaccine provided by the invention can induce a high-level neutralizing antibody, and widens targets for developing a novel multi-target antigen HSV-2 virus vaccine.

The present disclosure relates to an azide-modified fluorescent π-conjugated polymer and a DNA-modified π-conjugated fluorescent nanoparticle-based protein detection imaging method capable of signal rapid amplification and high throughput. The present disclosure prepares oligonucleotide-modified fluorescent π-conjugated polymers (OCPNs) based on the azide-modified fluorescent π-conjugated polymer. The OCPNs have ultrahigh fluorescence luminance and extremely high detection sensitivity, and can complete detection and imaging of targets in different abundances without the need of an additional fluorescence signal amplification step. In addition, a rapid and specific targeting effect can be achieved with an extremely small dosage and an entire staining and imaging process can be shortened, so that the OCPNs achieve an extremely high imaging efficiency during multi-color imaging and thus exhibit great application prospects.

The present disclosure features useful compositions and methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods of use for PRKAG2 antibody oligonucleotide conjugates (AOC).

Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and / or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-α) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

The present disclosure provides an aptamer capable of inhibiting the activity of a strand-displacing DNA polymerase, the aptamer including: an oligonucleotide region 1 comprising a sequence in which a sequence X1a is linked to the 3'-end of a first sequence or the sequence X1a is linked to the 3'-end of a mutant sequence of the first sequence; and an oligonucleotide region 2 comprising a sequence in which a sequence X1b is linked to the 5'-end of a second sequence or the sequence X1b is linked to the 5'-end of a mutant sequence of the second sequence. The present disclosure also provides: a composition and a kit each containing the aptamer; and a method for amplifying a nucleic acid using the composition or the kit.

Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Among other tilings, the present disclosure provides various technologies including chirally controlled oligonucleotide compositions and technologies for manufacturing and using such oligonucleotide compositions. In some embodiments, the present disclosure provides technologies useful for allele-specific knockdown of mutant Huntingtin transcripts. In some embodiments, the present disclosure provides technologies usefill for reducing the expression, level, amount, and / or activity of mutant Huntingtin transcripts or products thereof. In some embodiments, the present disclosure provides methods for treating Huntington's disease.