Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

The present invention relates to very short heavily modified oligonucleotides which target and inhibit microRNAs in vivo, and their use in medicaments and pharmaceutical compositions.

The present disclosure provides oligonucleotide compositions that target the covalently closed circular (ccc) DNA of hepatitis B virus (HBV). Also disclosed herein are methods for treating a subject diagnosed with, or suspected of having an HBV infection and/or an HBV-associated disorder, e.g., chronic hepatitis B infection, liver failure or cirrhosis and hepatocellular carcinoma.

The present embodiments provide methods, compounds, and compositions for treating, preventing, ameliorating, or slowing progression of retinitis pigmentosa (RP), such as autosomal dominant retinitis pigmentosa (AdRP) by administering a P23H rhodopsin specific inhibitor to a subject. The present embodiments provided herein are directed to compounds and compositions useful for treating, preventing, ameliorating, or slowing progression of retinitis pigmentosa (RP), such as autosomal dominant retinitis pigmentosa (AdRP). In certain embodiments, P23H rhodopsin inhibitors provided herein are allele-specific antisense compounds targeted to a P23H mutant allele that are capable of selectively inhibiting expression of P23H rhodopsin mutant protein to a greater extent than wild-type protein. In certain embodiments, administration of the allele specific antisense compounds in a subject having AdRP results in selective inhibition of P23H rhodopsin and allows the normal protein produced from the wild-type allele to maintain rod survival and function in the subject.

A blocking oligonucleotide (10, 10A, 10A, 10A, 10B, 10C, 10D, 10E) comprises a 3-end complementary sequence (13) complementary to a 3-end sequence (23) of a globin mRNA molecule (20; 20A, 20B) and a poly-A complementary sequence (12) of at least one nucleotide complementary to at least a portion of a poly-A sequence (22) of the globin mRNA molecule (20, 20A, 20B). The blocking oligonucleotide (10, 10A, 10A, 10A, 10B, 10C, 10D, 10E) is capable of inhibiting binding of a reverse transcription anchored poly-T primer (30) to the globin mRNA molecule (20, 20A, 20B) and thereby significantly reducing synthesis of globin cDNA from globin mRNA molecules (20, 20A, 20B) present in a sample. This high reduction of globin cDNA by the blocking oligonucleotide (10, 10A, 10A, 10A, 10B, 10C, 10D, 10E) is achieved without any significant degradation of mRNA molecules present in the sample.

The invention provides compositions comprising nucleic acid complexes for use in screening compounds based on their ability to modulate binding interactions, wherein the compounds are barcoded.

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.

Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Provided herein are hybrid oligonucleotides comprising a region that promotes cleavage of a nucleic acid and a region that protects a nucleic acid from exonuclease activity. Such hybrid oligonucleotides are useful for modulating the expression of genes. Related compositions and methods are also provided. In some embodiments, methods are provided for treating a disease, such as by administering a hybrid oligonucleotide.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, the present invention provides compounds comprising oligonucleotides. In certain embodiments, such oligonucleotides comprise a region having a gapmer sugar motif. In certain embodiments, oligonucleotides comprise one or more type of modified sugar moieties and/or naturally occurring sugar moieties arranged along an oligonucleotide or region thereof in a defined pattern or sugar modification motif.