Abstract: This invention provides therapeutic and diagnostic agent delivery vehicles, including viral vectors, that are complexed to a targeting moiety by coordinate covalent linkages mediated by a transition metal ion. The complex is typically formed with a transition metal ion that is in a kinetically labile oxidation state; after the complex is formed, the oxidation state of the transition metal ion is changed to one that renders the complex kinetically stable. The use of a coordinate covalent linkage to attach the targeting moiety to the delivery vehicle provides the ability to readily attach a different targeting moiety to a delivery vehicle without modifying the delivery vehicle itself. This flexibility is achieved without sacrificing stability of the complex.

Abstract: Methods and compositions for the tretament of ocular disease with a cyclin dependent kinase inhibitor are provided.

Abstract: A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.

Abstract: Methods and composition for the treatment of ocular disease with a cyclin dependent kinase inhibitor are provided.

Abstract: Methods for purging stem cell products of tumor cells and for treating an individual having a disease which is treated by myeloablative therapy and stem cell rescue using a purged product are provided.

Abstract: The present invention provides an apparatus and method to diminish the pre-existing immune response to the administration of a therapeutic virus by the selective elimination of antiviral antibodies from the serum. The present invention provides a chromatographic material for the elimination of such antibodies. The invention further provides plasmapheresis apparatus comprising this material. The invention further provides methods for the employment of such apparatus as part of therapeutic treatment regiments.

Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention.

Abstract: This invention provides methods of regulating gene expression. An aptamer is positioned in a nucleic acid molecule along with a sequence encoding a transcriptional regulatory polypeptide. The aptamer disrupts translation of the transcriptional regulatory polypeptide when contacted with an aptamer-binding ligand. Gene expression levels can be either increased or decreased by the disclosed methods, depending on whether the transcriptional regulatory polypeptide is a repressor or activator, and the degree of the effect is dependent upon the dose of the ligand. Nucleic acid molecules, expression cassettes, expression vectors and cells useful in the gene regulation methods are also provided.

Abstract: This invention provides methods and compositions for enhancing transfer of an agent into a cell. The agents can include polypeptides, polynucleotides such as genes and antisense nucleic acids, and other molecules. In some embodiments, the agents are modulating agents that can modulate a cellular activity or function when introduced into the cell. The methods and compositions are useful for introducing agents into individual cells, as well as cells that are present as a tissue or organ.

Abstract: This invention provides methods and compositions for enhancing transfer of an agent into a cell. The agents can include polypeptides, polynucleotides such as genes and antisense nucleic acids, and other molecules. In some embodiments, the agents are modulating agents that can modulate a cellular activity or function when introduced into the cell. The methods and compositions are useful for introducing agents into individual cells, as well as cells that are present as a tissue or organ.

Abstract: Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

Abstract: A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.

Abstract: The instant invention addresses the need for a more accurate method of quantitating infectious viral particles in a population. The methods of the instant invention are based on the unexpected and surprising result that flow cytometry analysis of cells infected using specified ranges of viral particle concentration and/or adsorption time yields a more accurate measurement of infectious virus titer than traditional titration methods.

Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).

Abstract: A method and pharmaceutical composition for the treatment of cancer using a gene delivery system, such as a viral vector delivery system, comprising a therapeutic gene such as p53 or a retinoblastoma tumor suppressor gene wherein the gene delivery system is formulated in a buffer comprising a delivery-enhancing agent such as ethanol or a detergent.

Abstract: Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

Abstract: This invention provides a novel nucleic acid molecule encoding a prostate/colon tumor suppressor gene product. The means and methods for detecting mutations and/or loss of prostate/colon tumor suppressor gene are provided. Also included within the scope of this invention are methods of suppressing the neoplastic phenotype of cancer cells having a defect in the prostate/colon tumor suppressor gene product. The invention also includes the means and methods for treating the cancer by administering the prostate/colon tumor suppressor gene.

Abstract: The present invention is directed to a method of producing recombinant viral vectors at high titers incorporating a variety of important advancements over the art. The method of the present invention incorporates multiple features which provide enhanced production of viruses, particularly those viruses encoding exogenous transgenes. The specifically illustrated method describes a method for the high titer serum-free media production of recombinant replication defective adenoviruses containing an exogenous transgene. The invention provides methods of preparing microcarriers, methods for seeding bioreactors at high cell density, increasing the infectivity of the producer cells to the virus, methods to increase product yield through synchronization of the cell cycle of the producer cells, and methods to minimize the deleterious effects of exogenous transgenes. The invention further provides producer cells prepared by the process of the invention. The invention further provides viruses produced by the process.

Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).

Abstract: This invention provides a method of preventing or inhibiting the proliferation of a pathologically proliferating cell, wherein the pathological proliferation of the cell is the result of the absence of a functional retinoblastoma protein or polypeptide in the cell. The method requires contacting the cell with an effective amount of retinoblastoma protein or polypeptide. This method also is useful to prevent or treat retinoblastoma or a secondary cancer to retinoblastoma by administering to a patient a functional retinoblastoma protein or polypeptide.