151results about "Activity regulation" patented technology

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

Oligomeric compounds (including those that are antisense agents or portions thereof) are provided that comprise a modified oligonucleotide having at least one modified internucleoside linking group.SOLUTION: By an oligomeric compound comprising a modified oligonucleotide consisting of 12 to 70 linked nucleosides linked via internucleoside linking groups, wherein at least one nucleoside comprises a modified sugar moiety and wherein at least one internucleoside linking group is a phosphodiester or phosphorothioate internucleoside linking group.SELECTED DRAWING: Figure 1

The present disclosure relates generally to (CRISPR) RNA (crRNA) for the precision silencing of transcripts. In some embodiments, the crRNA are enriched for guanosine (G) nucleotides at key spacer positions, which is useful in enhancing the silencing efficacy of otherwise inefficient crRNA, thereby expanding the targeting spectrum of Cas13 endonucleases, e.g., Cas13b and Cas13d. In other embodiments, the crRNA comprise a spacer sequence having at least one nucleotide mismatch relative to the target RNA sequence, wherein the target RNA sequence is a wild-type transcript and / or a variant transcript (e.g., a transcript comprising a single nucleotide variant (SNV)). The present disclosure also provides RNA editing systems comprising the crRNA described herein in complex a Cas13 effector protein and a target RNA sequence, methods for the selective targeting of transcripts encoding proteins that are difficult to target, or are not amenable to pharmacological targeting, e.g., oncogenic fusion transcripts or oncogenic transcripts comprising single nucleotide variant(s), and methods for the design and selection of potent crRNA.

The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making modified nucleic acid donor templates for highly efficient and precise gene editing.

Disclosed herein are compositions comprising an oligonucleotide that inhibits the expression of MST1. The oligonucleotide includes a small interfering RNA (siRNA), as well as these compositions for use in methods of treating lung disorders

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

To provide high throughput assays for measuring adenovirus replication kinetics.SOLUTION: Recombinant adenovirus genomes containing a heterologous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. The recombinant adenovirus genomes, and recombinant adenoviruses produced by the disclosed genomes can be used, for example, in high- throughput assays to measure virus replication kinetics. Methods for measuring replication kinetics of a recombinant adenovirus are also described. In one aspect, provided are recombinant adenovirus genomes that include a heterologous ORF and a self-cleaving peptide coding sequence, both operably linked to and in the same reading frame as an endogenous adenovirus ORF.SELECTED DRAWING: None

The present disclosure provides antisense compounds, methods, and compositions for silencing C9ORF72 transcripts. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with C9ORF72 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with C9ORF72.

To provide modified compositions for use in CRISPR systems and methods of using them.SOLUTION: Described are length-modified and chemically-modified forms of crRNA and tracrRNA for use as reconstituted guide RNAs for interaction with Cas9 of CRISPR systems. The resultant length-modified and chemically-modified forms of crRNA and tracrRNA are economical to produce and can be tailored to have unique properties relevant to their biochemical and biological activity in the context of the CRISPR Cas9 endonuclease system.SELECTED DRAWING: Figure 10

Provided herein are double-stranded nucleic acid inhibitor molecules having a shortened sense strand with a stem loop structure and an antisense strand. Also provided are methods and compositions for reducing target gene expression and methods and compositions for treating a disease of interest.

The present invention relates to a modified siRNA with reduced off-target activity. The siRNA comprises a sense strand and an antisense strand containing a chemical modification represented by formula (I) or a tautomer modification thereof at at least one nucleotide position from positions 2 to 8 in the 5' region of the sense strand. The present invention also relates to a complex, pharmaceutical composition, cell, or reagent kit containing the siRNA, and pharmaceutical uses of the siRNA, the complex, and / or the pharmaceutical composition. The present invention also relates to compounds represented by formula (II) and formula (III) or tautomers thereof, and methods for preparing the same.

To provide effective nucleotide or chemical motifs of dsRNA molecules that are advantageous for inhibiting target gene expression, and to provide RNAi compositions suitable for therapeutic applications.SOLUTION: One aspect of the invention pertains to double-stranded RNA (dsRNA) agents capable of inhibiting the expression of a target gene. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules that are suitable for therapeutic use, and to methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., to treat various disease states.SELECTED DRAWING: None

The present invention relates to a novel method for stabilizing nucleic acid nanostructures by UV curing, in particular by cross-linking pyrimidine nucleotides.

The present application relates to a method for predicting possible off-targets in a gene editing process (e.g., a genome editing process) using a gene editing system.

Protected oligonucleotides are provided. Protected oligonucleotides with 5' and / or 3' splice sites are provided. Protected oligonucleotides with chemical modifications are provided. Methods of using protected oligonucleotides for genome editing with CRISPR nucleases, as well as kits for carrying out the methods, are also provided. The protected oligonucleotides include (a) a sequence complementary to the crRNA and (b) at least one chemically modified nucleotide.

This disclosure relates to a nucleic acid comprising a double stranded RNA molecule comprising sense and antisense strands and further comprising a single stranded DNA molecule covalently linked to at least the 5' end of either the sense or antisense RNA part of the molecule.

Provided herein are circularly structured guide RNAs with a circularization portion and a 3' to 3' linkage to the guide RNA.

In one embodiment, the present invention addresses the problem of providing a double-strand nucleic acid complex having a novel structure.　In one embodiment, the present invention pertains to a nucleic acid complex including a first nucleic acid strand and a second nucleic acid strand, wherein the first nucleic acid strand is a gapmer that (1) is capable of hybridizing at least a portion of a target transcription product, (2) has an antisense effect on the target transcription product, and (3) includes a middle region, a 5' wing region, and a 3' wing region, and the second nucleic acid strand includes at least one non-sugar modified middle region (first exposed region) that is complementary to a portion of the first nucleic acid strand and that comprises one non-sugar modified ribonucleoside or 2 or 3 successive non-sugar modified ribonucleosides that are linked by an inter-nucleoside bond, wherein the first nucleic acid strand is annealed to the second nucleic acid strand.

The present invention relates to small interfering nucleotides (siOligo), or derivatives or precursors thereof, complementary to the region comprising a point mutation in the mRNA of the mutated human P4HB gene, wherein said mutation is the point mutation A1178G causing the substitution of the amino acid Tyrosine (Y) for the amino acid Cysteine (C) at position 393 in humans (P4HB-Y393C), as well as pharmaceutical compositions comprising them and their use as a medicament, and in particular in the treatment of Cole-Carpenter Syndrome (CCS).

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3(SCA3).

The present invention refers to an oligonucleotide consisting of a core sequence of ATATTTAGGTCCAGCG (SEQ ID NO:1) or AATATTTAGGTCCAGCG (SEQ ID NO:2) and at least one additional nucleotide at the 3´-end and optionally at least one additional nucleotide at the 5´-end. At least one of the nucleotides of the oligonucleotide is modified, and the oligonucleotide binds to pre-mRNA of neuropilin 1 (NRP1, CD304). The invention is further directed to a pharmaceutical composition comprising such oligonucleotide. The pharmaceutical composition and the oligonucleotide are for use in a method of preventing and / or treating cancer, an ophthalmic disease, an autoimmune disorder and / or an immune disorder.

To provide self-delivering oligonucleotides that realize efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake, and efficient and specific tissue distribution, without formulation.SOLUTION: Provided herein is an oligonucleotide of at least 16 contiguous nucleotides, the oligonucleotide having a 5' end, a 3' end, and complementarity to a target, where (1) the oligonucleotide comprises alternating 2'-methoxy-ribonucleotides and 2'-fluoro-ribonucleotides; (2) the nucleotides at positions 2 and 14 from the 5' end are not 2'-methoxy-ribonucleotides; (3) the nucleotides are connected via phosphodiester or phosphorothioate linkages; and (4) the nucleotides at positions 1-6 from the 3' end or positions 1-7 from the 3' end are connected to adjacent nucleotides via phosphorothioate linkages.SELECTED DRAWING: None

Disclosed herein are compounds comprising a nucleic acid (A), their preparation, and their uses.

The present disclosure relates to modified guide RNAs with improved in vitro and in vivo activity in gene editing methods. [Selection diagram] None

This invention provides modified guide RNA (gRNA) with improved in vitro and in vivo activity for gene editing methods. [Solution] A genome editing tool is provided comprising a guide RNA (gRNA) having one or more shortened regions and / or substitutions. The shortened regions or substitutions may promote the synthesis of gRNA with higher yield and / or homogeneity, and / or improve the stability of the gRNA and gRNA / Cas9 complex, and may improve the activity of Cas9 (e.g., SaCas9, SpyCas9, and equivalents) for cleaving target DNA.

This provides useful regulatory elements in the fields of plant molecular biology and plant genetic engineering. [Solution] The present invention provides recombinant DNA molecules and constructs useful for regulating gene expression in plants, as well as their nucleotide sequences. The present invention also provides transgenic plants, plant cells, plant parts, and seeds containing recombinant DNA molecules operably linked to heterologous transcriptionable DNA molecules, and also provides methods for using them.

Provided herein are oligonucleotide formulations. In particular, it relates to formulations of oligonucleotide comprising oligonucleotide (such as ASO, siRNA, saRNA) and calcium, methods the preparation of the formulation, and use thereof. The oligonucleotide formulations have reduced in vivo acute toxicity (especially in central nervous system) and expanded in vivo safety window for the oligonucleotides especially the lipid conjugate, and thus having great application prospect.