Abstract: RNAi agents for inhibiting the expression of the alpha-1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.

Abstract: A multi-scale aggregation pattern analysis method for a complex traffic network is provided, which belongs to the field of the highway traffic network. Firstly, an adjacency matrix, a position attribute matrix, a distance weight matrix, a road grade matrix, and a time-phased traffic congestion degree matrix of a highway traffic network are calculated; secondly, a weight influence factor of the road network is incorporated based on a PageRank algorithm to determine order of critical nodes; finally, a two-dimensional decision diagram is drawn by two indicators: order of critical nodes and a shortest path distance. A new weighting matrix which accords with the actual situation of the road network is obtained by incorporating a position weight matrix, a distance weight matrix, a road grade weight matrix and a dynamic traffic congestion degree weight matrix based on a similarity matrix of the spectral clustering.

Abstract: Disclosed are a new AXL-targeting monoclonal antibody and antibody-drug conjugate. Also disclosed is a method for preparing said antibody and antibody-drug conjugate. The AXL antibody of the present invention can bind with purified human AXL protein and multiple AXL on tumor cell surface with high effectiveness and high specificity. Said humanized antibody also has high affinity and low immunogenicity. Said AXL antibody-drug conjugate has markable performance against tumors having high AXL expression.

Abstract: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Superoxide Dismutase 1 (SOD1) gene. The SOD1 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SOD1 gene. Pharmaceutical compositions that include one or more SOD1 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described SOD1 RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SOD1 gene expression and a reduction in SOD1 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including amyotrophic lateral sclerosis (ALS.).

Abstract: RNAi agents for inhibiting the expression of the alpha-1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.

Abstract: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Superoxide Dismutase 1 (SOD1) gene. The SOD1 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SOD1 gene. Pharmaceutical compositions that include one or more SOD1 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described SOD1 RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SOD1 gene expression and a reduction in SOD1 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including amyotrophic lateral sclerosis (ALS.

Abstract: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 (DUX4) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSID).

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: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 (DUX4) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).

Abstract: Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, capable of inhibiting Apolipoprotein C-III (also called APOC3, apoC-III, APOC-III, and APO C-III) gene expression, and compositions that include APOC3 RNAi agents. The APOC3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that include N-acetyl-galactosamine, to facilitate the delivery to cells, including to hepatocytes. Pharmaceutical compositions that include one or more APOC3 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the APOC3 RNAi agents in vivo provides for inhibition of APOC3 gene expression, and can result in lower triglycerides and/or cholesterol levels in the subject. The APOC3 RNAi agents can be used in methods of treatment of APOC3-related diseases and disorders, including hypertriglyceridemia, cardiovascular disease, and other metabolic-related disorders and diseases.

Abstract: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 (DUX4) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).

Abstract: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a matrix metallopeptidase 7 (MMP7) gene. The MMP7 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MMP7 gene. Pharmaceutical compositions that include one or more MMP7 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MMP7 RNAi agents to pulmonary cells, in vivo, provides for inhibition of MMP7 gene expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as idiopathic pulmonary fibrosis (IPF).

Abstract: The present disclosure relates to delivery vehicles that specifically and efficiently direct payloads to skeletal muscle cells in a subject, in vivo. The delivery vehicles 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 vehicles disclosed herein include RNAi agents, which can be linked or conjugated to the delivery vehicles, 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 vehicle 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: Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

Abstract: Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.