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: The present disclosure relates to delivery platforms that specifically and efficiently direct payloads to skeletal muscle cells in a subject, in vivo. The delivery platforms disclosed herein include targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-6) and pharmacokinetic/pharmacodynamic (PK/PD) modulators, to facilitate the delivery of payloads to cells, including to skeletal muscle cells. Suitable payloads for use in the delivery platforms disclosed herein include RNAi agents, which can be linked or conjugated to the delivery platforms, and when delivered in vivo, provide for the inhibition of gene expression in skeletal muscle cells. Pharmaceutical compositions that include the skeletal muscle cell delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a skeletal muscle cell is desirable.

Abstract: Synthetic ?v?6 integrin ligands of Formula I having serum stability and affinity for integrin ?v?6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin ?v?6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include ?v?6 integrin ligands and methods of use are also described.

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: The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand-targeted 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 conjugate) are further covalently linked to an RNAi trigger.

Abstract: Tetrapeptide linkers for reversibly linking a first compound to a amine-containing second compound are described. Compounds containing the tetrapeptide linkers and methods of using the tetrapeptide linkers are also described.

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: Tetrapeptide linkers for reversibly linking a first compound to a amine-containing second compound are described. Compounds containing the tetrapeptide linkers and methods of using the tetrapeptide linkers are also described.

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: The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand-targeted 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 conjugate) are further covalently linked to an RNAi trigger.