Abstract: Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In various embodiments, the invention also discloses compositions and devices that may further include a targeting agent, such as a polypeptide that is reactive with an FGF receptor (e.g., bFGF), or another ligand that binds to cell surface receptors on neuronal cells, or a support cell. The invention also discloses methods of promoting neuronal survival and regeneration via transfection of an axon as it grows through a device or composition of the present invention, or via transfection of a repair cell.

Abstract: A genetic package display system and methodology for probing protein-protein interactions that lead to cell transduction, selecting and/or identifying internalizing ligands, target cells and tissues which internalize known or putative ligands, and cell transduction facilitating peptides is provided. A ligand displaying genetic package that carries a selectable marker (e.g., reporter, selection, etc.) and presents a ligand on its surface is utilized to identify internalizing ligands, tranduction facilitating peptides, and/or a variety of cells and tissue types for the ability to be successfully transduced by the ligand displaying genetic package. Also provided are methods for evolving a ligand displaying package to facilitate gene delivery or delivery of any desired agent (e.g., pharmaceutical, polypeptide, peptide, etc.) into a cell and/or targeting cellular compartments such as the nucleus, endosome, chloroplast, mitochondria, etc.

Abstract: The present invention relates to gene therapy. In particular, therapeutic agents, therapeutic gene products, and compositions are disclosed. Various systems and methods useful in targeting and delivering non-native nucleotide sequences to specific cells are disclosed, wherein virus-antibody-ligand conjugates are used to facilitate targeting and delivery.

Abstract: Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity.

Abstract: The present invention relates to gene therapy. In particular, therapeutic agents, therapeutic gene products, and compositions are disclosed. Various systems and methods useful in targeting and delivering non-native nucleotide sequences to specific cells are disclosed, wherein virus-antibody-ligand conjugates are used to facilitate targeting and delivery.

Abstract: A genetic package display system and methodology for probing protein-protein interactions that lead to cell transduction, selecting and/or identifying internalizing ligands, target cells and tissues which internalize known or putative ligands, and cell transduction facilitating peptides is provided. A ligand displaying genetic package that carries a selectable marker (e.g., reporter, selection, etc.) and presents a ligand on its surface is utilized to identify internalizing ligands, tranduction facilitating peptides, and/or a variety of cells and tissue types for the ability to be successfully transduced by the ligand displaying genetic package. Also provided are methods for evolving a ligand displaying package to facilitate gene delivery or delivery of any desired agent (e.g., pharmaceutical, polypeptide, peptide, etc.) into a cell and/or targeting cellular compartments such as the nucleus, endosome, chloroplast, mitochondria, etc.

Abstract: Novel forms of vascular endothelial growth factor genes and the novel proteins encoded by these genes are disclosed. More particularly, novel forms of human VEGF-A which contain exon 6b and do not contain exon 6a are disclosed. Other novel forms of human VEGF-A contain exon 6b in addition to exon 6a. These novel forms of VEGF-A include VEGF-A138, VEGF-A162, and VEGF-A182. Such novel VEGF proteins may be used in treatment of the cardiovascular system and its diseases through effects on anatomy, conduit function, and permeability, and more particularly in the treatment of cardiovascular disease by stimulating vascular cell proliferation using a growth factor, thereby stimulating endothelial cell growth and vascular permeability.

Abstract: Preparations of conjugates of a receptor-binding internalized ligand and a cytocide-encoding agent and compositions containing such preparations are provided. The conjugates contain a polypeptide that is reactive with an FGF receptor, such as bFGF, or another heparin-binding growth factor, cytokine, or growth factor coupled to a nucleic acid binding domain. One or more linkers may be used in the conjugation. The linker is selected to increase the specificity, toxicity, solubility, serum stability, or intracellular availability, and promote nucleic acid condensation of the targeted moiety. The conjugates are complexed with a cytocide-encoding agent, such as DNA encoding saporin. Conjugates of a receptor-binding internalized ligand to a nucleic acid molecule are also provided.

Abstract: A method for identifying specific protein-protein (i.e., ligand/anti-ligand) interactions that internalize and are detected by transgene expression. A ligand displaying genetic package that carries a reporter or selectable marker and presents a ligand or putative ligand on its surface is utilized to screen cells displaying known or putative anti-ligands for the ability to successfully internalize the ligand displaying genetic package.

Abstract: Filamentous phage particles displaying a ligand on their surface are used to deliver a therapeutic gene to a cell. The ligand is a fusion protein with a phage capsid protein, covalently conjugated to phage particles, or complexed with modified phage particles.

Abstract: Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In various embodiments, the invention also discloses compositions and devices that may further include a targeting agent, such as a polypeptide that is reactive with an FGF receptor (e.g., bFGF), or another ligand that binds to cell surface receptors on neuronal cells, or a support cell. The invention also discloses methods of promoting neuronal survival and regeneration via transfection of an axon as it grows through a device or composition of the present invention, or via transfection of a repair cell.

Abstract: Methods of treating tumors with preparations of conjugates of a receptor-binding internalized ligand and a cytocide-encoding agent are provided. The conjugates contain a polypeptide that is reactive with an FGF receptor, such as FGF2, or other ligand coupled to a nucleic acid binding domain. One or more linkers may be used in the conjugation. The linker is selected to increase the specificity, toxicity, solubility, serum stability, or intracellular availability, and promote nucleic acid condensation of the targeted moiety. The conjugates are complexed with a cytocide-encoding agent, such as DNA encoding saporin or a prodrug-encoding agent. Conjugates of a receptor-binding internalized ligand to a nucleic acid molecule are also provided.

Abstract: Preparations of conjugates of a receptor-binding internalized ligand and a cytocide-encoding agent and compositions containing such preparations are provided. The conjugates contain a polypeptide that is reactive with an FGF receptor, such as bFGF, or another heparin-binding growth factor, cytokine, or growth factor coupled to a nucleic acid binding domain. One or more linkers may be used in the conjugation. The linker is selected to increase the specificity, toxicity, solubility, serum stability, or intracellular availability, and promote nucleic acid condensation of the targeted moiety. The conjugates are complexed with a cytocide-encoding agent, such as DNA encoding saporin. Conjugates of a receptor-binding internalized ligand to a nucleic acid molecule are also provided.

Abstract: Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In various embodiments, the invention also discloses compositions and devices that may further include a targeting agent, such as a polypeptide that is reactive with an FGF receptor (e.g., bFGF), or another ligand that binds to cell surface receptors on neuronal cells, or a support cell. The invention also discloses methods of promoting neuronal survival and regeneration via transfection of an axon as it grows through a device or composition of the present invention, or via transfection of a repair cell.

Abstract: Novel forms of vascular endothelial growth factor genes and the novel proteins encoded by these genes are disclosed. More particularly, novel forms of human VEGF-A which contain exon 6b and do not contain exon 6a are disclosed. Other novel forms of human VEGF-A contain exon 6b in addition to exon 6a. These novel forms of VEGF-A include VEGF-A138, VEGF-A162, and VEGF-A182. Such novel VEGF proteins may be used in treatment of the cardiovascular system and its diseases through effects on anatomy, conduit function, and permeability, and more particularly in the treatment of cardiovascular disease by stimulating vascular cell proliferation using a growth factor, thereby stimulating endothelial cell growth and vascular permeability. The invention also relates to nucleic acids encoding such novel VEGF proteins, cells, tissues and animals containing such nucleic acids; methods of treatment using such nucleic acids; and methods relating to all of the foregoing.

Abstract: A method for identifying target cells and tissues which internalize known or putative ligands is provided. A ligand displaying genetic package that carries a reporter or selectable marker and presents a ligand on its surface is utilized to screen a variety of cells and tissue types for the ability to be successfully transduced by the ligand displaying genetic package.

Abstract: A genetic package display system is presented for selecting internalizing ligands for gene delivery. The genetic package carries a reporter, selectable marker, or a specifically detectable nucleic acid sequence and presents a ligand on its surface. More specifically, a library of potential ligands may be screened for the ability to successfully transduce target cells.

Abstract: Filamentous phage particles displaying a ligand on their surface are used to deliver a therapeutic gene to a cell. The ligand is a fusion protein with a phage capsid protein, covalently conjugated to phage particles, or complexed with modified phage particles.

Abstract: A genetic package display system and methodology for probing protein-protein interactions that lead to cell transduction, selecting and/or identifying internalizing ligands, target cells and tissues which internalize known or putative ligands, and cell transduction facilitating peptides is provided. A ligand displaying genetic package that carries a selectable marker (e.g., reporter, selection, etc.) and presents a ligand on its surface is utilized to identify internalizing ligands, tranduction facilitating peptides, and/or a variety of cells and tissue types for the ability to be successfully transduced by the ligand displaying genetic package. Also provided are methods for evolving a ligand displaying package to facilitate gene delivery or delivery of any desired agent (e.g., pharmaceutical, polypeptide, peptide, etc.) into a cell and/or targeting cellular compartments such as the nucleus, endosome, chloroplast, mitochondria, etc.

Abstract: Methods of modulating the export of a leaderless protein from a cell by contacting the cell with a compound that alters the binding of the leaderless protein and a transport molecule are provided. Transport molecules include gastrin binding protein/alpha subunit of mitochondrial fatty acid &bgr;-oxidation multienzyme complex (p70, GenBank Accession Nos. U04627/D16480), phosphotyrosine-independent ligand of the SH2 domain of p56lck (p62, GenBank Accession No. U46751), mitochondrial fatty acid &bgr;-oxidation trifunctional protein &bgr; subunit (TP-&bgr;) (p48, GenBank Accession No. D16481), actin related protein 3 (Arp3) (p48, GenBank Accession No. U29610), K-glypican (GenBank Accession No. X83577), tubulin (p50, GenBank Accession No. AF081484) and related polypeptides that are functionally equivalent in their role as leaderless protein trafficking components. Leaderless proteins include, for example, FGF-1, FGF-2, IL-1&agr;, IL-1&bgr;, CNTF, MIF, and HIV tat.