Abstract: Provided herein are oligonucleotides for inhibiting the expression of phospholamban (PLN) and methods of using the oligonucleotides for reducing PLN expression in a subject.

Abstract: The present invention relates to inhibitors, and compositions containing inhibitors, and uses of the same in the treatment or prevention of vascular and/or metabolic diseases.

Abstract: The present invention provides novel nucleic acid compound suitable for therapeutic use. Additionally, the present invention provides methods of making these compounds, as well as methods of using such compounds for the treatment of various diseases and conditions.

Abstract: The present invention relates to methods and compositions for editing a polynucleotide, e.g., a polynucleotide comprising a SNP associated with a disease or disorder.

Abstract: The present invention provides novel nucleic acid compounds suitable for therapeutic use. Additionally, the present invention provides methods of making these compounds, as well as methods of using such compounds for the treatment of various diseases and conditions.

Abstract: The present invention provides novel nucleic acid compounds suitable for therapeutic use. Additionally, the present invention provides methods of making these compounds, as well as methods of using such compounds for the treatment of various diseases and conditions.

Abstract: The present invention relates to inhibitors, and compositions containing inhibitors, and uses of the same in the treatment or prevention of a disease related to a disorder of haemostasis, such as haemophilia.

Abstract: The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.

Abstract: The present invention relates to inhibitors, and compositions containing inhibitors, and uses of the same in the treatment or prevention of diabetes.

Abstract: The invention provides compositions useful to knock down overexpression of UBE3A and treat conditions associated with Dup15q syndrome. The compositions include antisense oligonucleotides, preferably short oligonucleotides that are complementary to, and hybridize to, UBE3A transcripts in vivo. The ASOs prevent or inhibit successful translation of UBE3A mRNA into protein. Specifically, preferred embodiments include anti-UBE3A gapmers—oligos that include a central DNA portion flanked by RNA wings. When the gapmer hybridizes to UBE3A pre-mRNA or mRNA, the duplex hybrid recruits RNaseH, which cleaves, or digests, the UBE3A pre-mRNA or mRNA, preventing expression of the UBE3A protein. Because the ASOs prevent expression of the UBE3A protein, treatment with a composition including ASOs of the disclosure may be effective to knock down overexpression of UBE3A.

Abstract: The present invention relates to inhibitors, and compositions containing inhibitors, and uses of the same in the treatment or prevention of diabetes.

Abstract: Compositions, methods for making and using polynucleotide inhibitors modulating xanthine dehydrogenase expression or activity are provided.

Abstract: Disclosed are methods of treating a subject with a neurological disease associated with a splicing defect caused by TDP-43 proteinopathies, comprising administering to said subject an agent to increase expression levels and/or stability of hnRNP L, thereby attenuating and/or repairing the splicing defect. The disclosure also relates to nucleic acids targeting heterogeneous nuclear ribonucleoprotein L (hnRNP L), and their use.

Abstract: The invention provides non-opioid pain therapeutic compositions that include an antisense oligonucleotide (ASO) complementary to an identified target on a NaV channel mRNA. The ASO hybridizes to its target RNA and forms a duplex that recruits RNase H to degrade the RNA, thereby downregulating NaV channel synthesis, which inhibits the neuron's ability to contribute to the perception of pain. The ASO targets one of the specific identified targets, and may be provided as a gapmer that includes a central DNA segment flanked by modified RNA wings. When the composition is delivered to dorsal root ganglion (DRG) neurons in vitro, the DRG neurons exhibit a dose-dependent knockdown of NaV1.7, NaV1.8, or NaV1.9.

Abstract: The present disclosure provides, among other things, MuSK-targeting oligonucleotide compositions that alter the splicing of MuSK transcripts through exon skipping, and methods of treating diseases with said compositions.

Abstract: The invention provides non-opioid pain therapeutic compositions that include an antisense oligonucleotide (ASO) complementary to an identified target on a NaV channel mRNA. The ASO hybridizes to its target RNA and forms a duplex that recruits RNase H to degrade the RNA, thereby downregulating NaV channel synthesis, which inhibits the neuron's ability to contribute to the perception of pain. The ASO targets one of the specific identified targets, and may be provided as a gapmer that includes a central DNA segment flanked by modified RNA wings. When the composition is delivered to dorsal root ganglion (DRG) neurons in vitro, the DRG neurons exhibit a dose-dependent knockdown of NaV1.7, NaV1.8, or NaV1.9.

Abstract: The present application relates to oligonucleotides (e.g., antisense oligonucleotides such as gapmers) designed to target FXN RNAs and targeting complexes for delivering the oligonucleotides to cells (e.g., muscle cells) and uses thereof, particularly uses relating to treatment of disease. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload increases expression or activity of a FXN allele comprising a disease-associated-repeat.

Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against PHD2 gene expression.

Abstract: Disclosed herein are UNC13A oligonucleotides with one or more spacers or without a spacer. In various embodiments, UNC13A oligonucleotides with spacer(s) reduce mis-spliced UNC13A transcripts and increase full length UNC13A transcripts, thereby imparting therapeutic efficacy against neurological diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or Alzheimer's disease (AD).

Abstract: The present invention relates to methods and compositions for editing a polynucleotide, e.g., a polynucleotide comprising a SNP associated with a disease or disorder.