Abstract: Methods for controlling and regulating engulfment, uptake and/or transcellular transport at a stage following initial engagement of an agent to the endothelium are provided, based on the identification of CAM-mediated endocytosis and the sphingomyelin/ceramide pathway as active steps in transcellular TEM. Administration of regulators relating to the identified pathways, such as NHE1, sphingomyelinases, acid sphingomyelinase and ceramide, permit control and regulation of uptake and transcellular transport. Control and regulation of uptake and/or transcellular transport is applicable in strategies to modulate inflammation, provide controlled and/or targeted delivery of agents, control pathogenic invasion, recover action of an inhibited CAM-mediated uptake or transendothelial pathway, or provide uptake or transendothelial transport by targeting cell surface markers other than ICAM-1.

Abstract: Methods for controlling and regulating engulfment, uptake and/or transcellular transport at a stage following initial engagement of an agent to the endothelium are provided, based on the identification of CAM-mediated endocytosis and the sphingomyelin/ceramide pathway as active steps in transcellular TEM. Administration of regulators relating to the identified pathways, such as NHE1, sphingomyelinases, acid sphingomyelinase and ceramide, permit control and regulation of uptake and transcellular transport. Control and regulation of uptake and/or transcellular transport is applicable in strategies to modulate inflammation, provide controlled and/or targeted delivery of agents, control pathogenic invasion, recover action of an inhibited CAM-mediated uptake or transendothelial pathway, or provide uptake or transendothelial transport by targeting cell surface markers other than ICAM-1.

Abstract: The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.

Abstract: The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

Abstract: The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.

Abstract: The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

Abstract: A system and method for transcellular transport of compositions containing agents (e.g., research, analytical, reporter or molecular probes, diagnostic and therapeutic agents, biologically active agents, research agents, analytical agents, imaging agents, monitoring agents, enzymes, proteins, peptides, nucleic acids, lipids, sugars, hormones, lipoproteins, chemicals, viruses, bacteria, cells, including modified cells, biosensors, markers, antibodies and/or ligands) across the gastrointestinal epithelial layer including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes an anti-ICAM antibody targeting moiety, specific for targeting ICAM-1. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use 10 of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

Abstract: A system for targeted delivery of agents (e.g., molecular probes, diagnostic agents, therapeutic agents, imaging agents, research or analytical compounds, enzymes, peptides, proteins, lipids, lipoproteins, sugars, hormones, vitamins, nucleic acids, viruses, bacteria, and/or cells) including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes a targeting moiety of one of peptides ?3, 2?3, 3?3, A1, B7, B8, B9, B1O, and D6, specific for targeting ICAM-I. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

Abstract: A system and method for transcellular transport of compositions containing agents (e.g., research, analytical, reporter or molecular probes, diagnostic and therapeutic agents, biologically active agents, research agents, analytical agents, imaging agents, monitoring agents, enzymes, proteins, peptides, nucleic acids, lipids, sugars, hormones, lipoproteins, chemicals, viruses, bacteria, cells, including modified cells, biosensors, markers, antibodies and/or ligands) across the gastrointestinal epithelial layer including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes an anti-ICAM antibody targeting moiety, specific for targeting ICAM-1. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: A system and method for transcellular transport of compositions containing agents (e.g., research, analytical, reporter or molecular probes, diagnostic and therapeutic agents, biologically active agents, research agents, analytical agents, imaging agents, monitoring agents, enzymes, proteins, peptides, nucleic acids, lipids, sugars, hormones, lipoproteins, chemicals, viruses, bacteria, cells, including modified cells, biosensors, markers, antibodies and/or ligands) across the gastrointestinal epithelial layer including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes an anti-ICAM antibody targeting moiety, specific for targeting ICAM-1. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: The invention provides a composition comprising transthyretin and an ICAM-1 targeting agent, wherein the transthyretin and ICAM-1 targeting agent are coupled together, as well as methods of preparing such compositions. The invention further provides a diabody capable of binding specifically to ICAM-1 and transthyretin. The invention also provides a method of use of such composition in the manufacture of a medicament for treating an amyloid-? related neurodegenerative disease, comprising administering to a subject a composition comprising transthyretin coupled to an ICAM-1 targeting agent in an amount effective to treat the neurodegenerative disease, wherein the composition is administered to the subject outside of the blood-brain barrier.

Abstract: A system and method for transcellular transport of compositions containing agents (e.g., research, analytical, reporter or molecular probes, diagnostic and therapeutic agents, biologically active agents, research agents, analytical agents, imaging agents, monitoring agents, enzymes, proteins, peptides, nucleic acids, lipids, sugars, hormones, lipoproteins, chemicals, viruses, bacteria, cells, including modified cells, biosensors, markers, antibodies and/or ligands) across the gastrointestinal epithelial layer including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes an anti-ICAM antibody targeting moiety, specific for targeting ICAM-1. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: A system for targeted delivery of agents (e.g., molecular probes, diagnostic agents, therapeutic agents, imaging agents, research or analytical compounds, enzymes, peptides, proteins, lipids, lipoproteins, sugars, hormones, vitamins, nucleic acids, viruses, bacteria, and/or cells) including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes a targeting moiety of one of peptides ?3, 2?3, 3?3, A1, B7, B8, B9, B1O, and D6, specific for targeting ICAM-I. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.

Abstract: The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use 10 of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.