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.

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: 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.

Abstract: The present disclosure relates to antisense oligonucleotides (ASOs) directed to mRNA transcripts of CD274 to cause downregulation of programmed death-ligand 1 (PD-L1) expression in humans. The ASO 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 ASOs and uses of or methods of using the ASOs for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

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 an EC50 that is less than 100 nM.