Abstract: The present invention relates to novel VEGF protein products, and nucleic acids encoding these novel protein products, comprising exons 1-6 and 8 of the VEGF gene, and derivatives thereof, and these uses in treating the cardiovascular system and its diseases through effects on anatomy, conduit function, and permeability. VEGF145 and its derivatives have been found to be active mitogens for vascular endothelial cells and to function as angiogenic factors in-vivo. VEGF145 and its derivatives have novel properties compared with previously characterized VEGF species with respect to cellular distribution, susceptibility to oxidative damage, and extra-cellular matrix (ECM) binding ability. The present invention also relates to derivatives of VEGF145 which have altered properties in that they have altered biological activity and altered heparin-binding activity when compared to VEGF145.

Abstract: The present invention provides, among other things, a method of inhibiting an immune response to a recombinant vector, such as a viral vector, specifically an adenoviral vector. The method comprises contacting a cell with (i) a recombinant vector, preferably a viral vector, most preferably an adenoviral vector, comprising a transgene and (ii) a means of inhibiting an immune response to the recombinant vector selected from the group consisting of a TNF receptor fusion protein, a Fas receptor fusion protein, an IFN receptor fusion protein, a gene encoding a TNF receptor fusion protein, a gene encoding a Fas receptor fusion protein, and a gene encoding an IFN receptor fusion protein, whereupon an immune response to the recombinant vector is inhibited. In this regard, the present invention also provides a recombinant vector and a composition for use in the method.

Abstract: The invention provides a method of treating a disease or pathological condition resulting in apoptotic cell death. The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. Also provided is a method of prolonging the in vivo survival of transplanted cells for the treatment of a disease or pathological condition. The method includes increasing the activity of Bcl-2 in a population of cells and transplanting the population of cells having increased Bcl-2 activity into a subject. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. A method to enhance the sensitivity of malignant cells to therapy is provided that includes decreasing the activity of Bcl-2 in the malignant cells.

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the &bgr;2-microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Abstract: A method of preventing a respiratory infection by administering DNA which encodes IFN is provided. Also provided is a therapy for the prevention of a respiratory infection containing DNA which encodes IFN.

Abstract: The use of professional antigen presenting cells genetically modified to enhance expression of an immunostimulatory cytokine is disclosed for the treatment of individuals having tumors or infections. The genetically modified professional antigen presenting cells are injected directly at or near the site of the tumor or infection. Preferred professional antigen presenting cells include dendritic cells, and preferred immunostimulatory cytokines include interleukins such as IL-12.

Abstract: An improved method for the production of monoclonal antibodies is disclosed.

Abstract: Methods of prophylactic and therapeutic immunization of an individual against pathogen infection, diseases associated with hyperproliferative cells and autoimmune diseases are disclosed. The methods comprise the steps of administering to cells of an individual, a nucleic acid molecule that comprises a nucleotide sequence that encodes a protein which comprises at least one epitope that is identical or substantially similar to an epitope of a pathogen antigen, a hyperproliferative cell associated protein or a protein associated with autoimmune disease respectively. In each case, nucleotide sequence is operably linked to regulatory sequences to enable expression in the cells. The nucleic acid molecule is free of viral particles and capable of being, expressed in said cells. The cells may be contacted cells with a cell stimulating agent. Methods of prophylactically and therapeutically immunizing an individual against HIV are disclosed.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: RNA cancer vaccines and methods for their use are described. The vaccines are comprised of viral liposomes comprising nucleic acid, preferably RNA, encoding a tumor-associated antigen. The viral liposomes may be formed by the fusion of HVJ reagents with nonviral reagents. The vaccine may be administered subcutaneously, intradermally, intramuscularly or into an organ. The vaccine may be administered to induce a host normal cell to express the tumor associated antigen.

Abstract: The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of the delivered gene and for in vivo secretion of the therapeutic protein from transduced muscle cells such that systemic delivery is achieved.

Abstract: The use of recombinant adeno-associated virus (AAV) virions for the treatment of solid tumors is disclosed. The invention provides for the use of recombinant AAV virions to deliver an AAV vector containing a drug-susceptibility gene and a second gene capable of providing an ancillary effect to solid tumor cells. The second gene can be used to enhance the immunogenicity of the transduced tumor cell. Alternatively, the second gene can be used to provide a tumorstatic effect. The invention also provides for the use of recombinant AAV virions to deliver an interferon gene, or a tumor suppressor gene to provide a therapeutic effect in a transduced tumor cell.