Abstract: Methods and pharmaceutical compositions for modifying cells of a mammalian recipient with DNA encoding a secreted protein such as human interferon in situ are provided. The methods include forming a secreted protein expression system in vivo or ex vivo and administering the expression system to the mammalian recipient. The expression system and methods are useful for the localized and systemic delivery of interferons in situ.

Abstract: This invention relates to a method for systemic immune activation which is effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in a mammal. The method is particularly effective for protecting a mammal from a disease including cancer, a disease associated with allergic inflammation, or an infectious disease. Also disclosed are therapeutic compositions useful in such a method.

Abstract: A herpesvirus saimiri (HVS) vector which has inserted therein at least a part of a gene encoding an envelope protein of HIV for use in delivering said protein to a specific cell population such as T cell lymphocytes and/or macrophages. The invention also provides a vaccine comprising the recombinant vector.

Abstract: The invention relates to methods of and compositions for vaccinating a mammal against a disease, wherein a mixture is administered which includes (i) a nucleic acid which encodes a first epitope and (ii) a peptide containing a second epitope such that both of the nucleic acid and the second epitope are taken up by and the nucleic acid is expressed in a professional antigen presenting cell of the mammal, and the first and second epitopes are processed in the cell such that an immune response is elicited in the mammal to the epitopes.

Abstract: One major problem with adenovirus gene therapy has been the T-cell mediated immune response elicited by inoculation of adenovirus, which leads to rapid clearance of the virus and loss of transgene expression. In the instant invention, the immune response to a virus is prevented by pre-treatment with adenovirus, adenoassociated virus or herpes virus infected antigen-presenting cell (APC) expressing Fas ligand with induced T-cell tolerance. Administration of AdCMVLacZ after tolerance resulted in prolonged expression of LacZ in tolerized animals compared to control treated animals. In control, but not tolerized animals, there was proliferation of CD3+ T-cell in the spleen in response to AdCMVLacZ treatment. Tolerance induction is also indicated by decreased production of interferon-&ggr; and IL-2 by peripheral T-cells isolated from treated animals after stimulation with the adenovirus infected APCs.

Abstract: Cells transformed to express on their surface a component which binds to an Fc receptor of an effector cell are disclosed. Also disclosed are expression vectors used to transform the cells. Once transformed, the cells bind to effector cells via the Fc receptor of the effector cell to stimulate an effector cell mediated immune response.

Abstract: A method for introducing and expressing genes in animal cells is disclosed comprising infecting the animal cells with live invasive bacteria, wherein the bacteria contain a eukaryotic expression cassette encoding the gene. The gene may encode, e.g., a vaccine antigen, a therapeutic agent, an immunoregulatory agent or an anti-sense RNA or a catalytic RNA.

Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Abstract: The subject invention concerns a recombinant adeno-associated virus vector characterized as being capable of delivering and expressing at least one mammalian gene into a genome of a mammalian host cell such that the expression of the gene is regulated in a tissue specific manner by cis-acting regulatory and promoter elements of the gene. A method of using this recombinant adeno-associated virus vector for therapeutic purposes is also provided.

Abstract: The present invention relates to a retroviral vector encoding heterologous genes particularly for gene therapy of genetic defects or viral infections.

Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Abstract: A composition for genetic manipulation of cells comprises a liposome comprised of lipid material, and adeno-associated viral (AAV) material. Typically, the AAV material is plasmid, and comprises one or more terminal repeats of the AAV genome. Methods are disclosed for introducing DNA into cells using AAV/liposome complexes. The DNA is introduced and expressed in'stem cells, T cells, primary tumor cells, tumor cell lines and dendritic cells or other antigen-presenting cells. Such transfected cells are used in therapeutic methods to treat subjects with cancer or microbial infections. Dendritic cells with DNA encoding tumor or viral antigens and are used to treat subjects with tumors or viral infections by administration in vivo or by activation of antigen-specific lymphocytes ex vivo followed by administration of those lymphocytes to the subject.

Abstract: Immunostimulatory compositions that contain fused cells formed by fusion between dendritic cells and non-dendritic cells, methods of using these compositions, and methods of generating dendritic cell hybrids.

Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13-19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.

Abstract: The present invention relates to nucleic acid molecules encoding expression products involved in the Responder function, which contributes to the phenomenon of transmission ratio distortion. The present invention also relates to regulatory regions of the genes corresponding to the nucleic acid molecules. The present invention further relates to recombinant DNA molecules and vectors comprising the nucleic acid molecules and/or regulatory regions as well as to host cells transformed therewith. Additionally, the present invention relates to transgenic animals, comprising the nucleic acid molecules, recombinant DNA molecules or vectors stably integrated into their genome. The various embodiments of the invention have a significant impact on breeding strategies by allowing for the specific selection of genetic traits and in particular of sex. Further, the present invention finds applications in the development of contraceptive.

Abstract: Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes.

Abstract: The invention provides a transgenic swine having a transgene encoding a human HLA-DQ or HLA-DR protein, and the swine cells thereof. The invention also provides a graft derived from the transgenic swine, in particular a graft-organ or a graft-tissue, which is useful for grafting into a human recipient.

Abstract: The invention demonstrates that the transcription factor XBP-1 is a regulator of hepatocyte growth, plasma cell differentiation and T cell subset activity. Methods for identifying modulators of hepatocyte growth, plasma cell differentiation and/or T cell subset activity, using XBP-1-containing indicator compositions or XBP-1-deficient cells, are provided. Methods of modulating hepatocyte growth, plasma cell differentiation and/or T cell subset activity (e.g., Th2 cytokine production) using agents that modulate the activity of XBP-1 are also provided. Methods for diagnosing disorders associated with aberrant hepatocyte growth, plasma cell differentiation and/or T cell subset activity, by assessing a change in XBP-1 expression, are also provided. XBP-1 deficient cells, animals and embryos, as well as kits for the methods of the invention, are also provided by the invention.

Abstract: Methods for modulating T cell responses by manipulating intracellular signals associated with T cell costimulation are disclosed. The methods involve inhibiting or stimulating the production of at least one D3-phosphoinositide in a T cell. Production of D3-phosphoinositides can be manipulated by contacting a T cell with an inhibitor or activator of phosphatidylinositol 3-kinase. Inhibitors of phosphatidylinositol 3-kinase for use in the methods of the invention include wortmannin and quercetin, or derivatives or analogues thereof. The methods of the invention can further comprise modulating other intracellular signals associated with costimulation, such as protein tyrosine phosphorylation, for example by modulating the activity of a protein tyrosine kinase or a protein tyrosine phosphatase in the T cell.

Abstract: Stable pluripotent trophoblast stem (TS) cell lines and uses of the cell lines are described. The cell lines comprise cells that (i) are capable of indefinite proliferation in vitro in an undifferentiated state, and (ii) are capable of differentiation into cells of the trophoblast lineage in vivo.