Abstract: Disclosed herein is an oligonucleotide conjugate or complex thereof, comprising a modified oligonucleotide having sequence independent antiviral activity against hepatitis B, a liver targeting agent, and a linker connecting the liver targeting agent to a 3? end and/or a 5? end of the modified oligonucleotide or complex thereof. The oligonucleotide conjugate may be incorporated into a pharmaceutical composition for treating a liver disease or disorder such as hepatitis B.

Abstract: Disclosed herein are compounds of Formula I?: or a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising such compounds, and methods of treating disease by administering or contacting a subject with one or more of the above compounds.

Abstract: Disclosed herein are compounds of Formula I: or a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising such compounds, and methods of treating disease by administering or contacting a subject with one or more of the above compounds.

Abstract: Disclosed herein are compounds of Formula I?: or a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising such compounds, and methods of treating disease by administering or contacting a subject with one or more of the above compounds.

Abstract: Various embodiments provide STOPS™ polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS™ modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS™ modified oligonucleotides, as determined by HBsAg Secretion Assay, is greater than that of a reference compound.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Oligonucleotides that target hepatitis B virus (HBV) viral sequences, such as rcDNA, cccDNA, and HBV transcripts, are described herein. In addition, compositions and kits comprising such oligonucleotides are further described. Further disclosed herein are uses of such oligonucleotides and compositions to reduce rcDNA to cccDNA conversion, reduce cccDNA levels, and/or treat an HBV infection.

Abstract: The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified 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 capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

Abstract: A method of making a compound represented by Formula (I): includes a reducing step, a protecting step, and a phosphitylating step, where X is NH; Y is OCF3, —O(CR42)aCR43, —O(CR42)bOCR43, or —O(CR42)b—CR4?CR42; Z is H; B is adenine (A), guanine (G), thymine (T), cytosine (C), uracil (U), 5-methylcytosine (5-me-C), or a protected version of A, G, T, C, U, or 5-me-C; each R1 is independently C1-6 alkyl or cycloalkyl; R2 is CH2CH2CN or C1-6 alkyl; or R1 and R2 together form an optionally substituted C1-6 cycloalkyl; R3 is H or PG; PG is a protecting group; R4 is independently in each instance H or F; a is 1 or 2; and b is 1, 2, or 3.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed herein are compounds of the Formula (I) and pharmaceutically acceptable salts thereof: (I) where the variables in Formula (I) are described herein. Methods of synthesizing such compounds and methods of using them to treat diseases and/or conditions such as a Picornaviridae, Flaviviridae, Filoviridae, Pneumoviridae and/or Coronaviridae viral infections are also disclosed.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: The present disclosure relates to compounds and compositions containing 5?-phosphoramidite nucleoside monomers of formulae (I) and (II), and methods of making and use, wherein the substituents are as defined in the appended claims.

Abstract: Various embodiments provide STOPS™ polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS™ modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS™ modified oligonucleotides, as determined by HBsAg Secretion Assay, is greater than that of a reference compound.

Abstract: Disclosed herein are compounds of the Formula (I) and pharmaceutically acceptable salts thereof: (I) where the variables in Formula (I) are described herein. Methods of synthesizing such compounds and methods of using them to treat diseases and/or conditions such as a Picornaviridae, Flaviviridae, Filoviridae, Pneumoviridae and/or Coronaviridae viral infections are also disclosed.

Abstract: The present disclosure relates to the field of pharmaceutical compounds and preparations and method of their use in the treatment of disease. Described are antisense oligonucleotide (ASO) molecules, compositions containing the same, and uses thereof for treating or preventing coronavirus infections. In particular, the present disclosure provides specific ASOs that are effective against a broad spectrum of coronaviruses, and especially the ?-coronaviruses, including SARS-CoV-2, the causative agent of COVID-19.

Abstract: The present disclosure relates to small interfering RNA (siRNA) molecules directed to mRNA transcripts of CD274 to cause downregulation of programmed death-ligand 1 (PD-L1) expression in humans. The siRNA can be constructed of unmodified nucleotides or modified nucleotides that exhibit modified sugars, nucleobases, linkages, or covalently bound targeting moieties. Also disclosed herein are pharmaceutical compositions of siRNAs and uses of or methods of using the siRNAs for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.