Abstract: RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2? (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2? RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2? RNAi triggers to tumor cells in vivo provides for inhibition of Hif2? gene expression and treatment of cancer.

Abstract: Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

Abstract: RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2? (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2? RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2? RNAi triggers to tumor cells in vivo provides for inhibition of Hif2? gene expression and treatment of cancer.

Abstract: RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2? (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2? RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2? RNAi triggers to tumor cells in vivo provides for inhibition of Hif2? gene expression and treatment of cancer.

Abstract: Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

Abstract: Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

Abstract: We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.

Abstract: RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2? (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2? RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2? RNAi triggers to tumor cells in vivo provides for inhibition of Hif2? gene expression and treatment of cancer.

Abstract: Described are improved disulfide-containing alkyne linking agents having have branched disulfides. The improved linking agents exhibit improved stability. The linking agents are useful for attachment of oligonucleotides to targeting groups or delivery agents.

Abstract: RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2? (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2? RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2? RNAi triggers to tumor cells in vivo provides for inhibition of Hif2? gene expression and treatment of cancer.

Abstract: Described are improved disulfide-containing alkyne linking agents having have branched disulfides. The improved linking agents exhibit improved stability. The linking agents are useful for attachment of oligonucleotides to targeting groups or delivery agents.

Abstract: Described are improved disulfide-containing alkyne linking agents having have branched disulfides. The improved linking agents exhibit improved stability. The linking agents are useful for attachment of oligonucleotides to targeting groups or delivery agents.

Abstract: Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

Abstract: RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2? (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2? RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2? RNAi triggers to tumor cells in vivo provides for inhibition of Hif2? gene expression and treatment of cancer.

Abstract: We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.

Abstract: Described are improved disulfide-containing alkyne linking agents having have branched disulfides. The improved linking agents exhibit improved stability. The linking agents are useful for attachment of oligonucleotides to targeting groups or delivery agents.

Abstract: We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

Abstract: The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

Abstract: We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.