Abstract: The invention relates to methods for targeting an exogenous polynucleotide or exogenous complementary polynucleotide pair to a predetermined endogenous DNA target sequence in a eukaryotic cell by homologous pairing, particularly for altering an endogenous DNA sequence, such as a chromosomal DNA sequence, typically by targeted homologous recombination. In certain embodiments, the invention relates to methods for targeting an exogenous polynucleotide having a linked chemical substituent to a predetermined endogenous DNA sequence in a metabolically active eukaryotic cell, generating a DNA sequence-specific targeting of one or more chemical substituents in an intact nucleus of a metabolically active eukaryotic cell, generally for purposes of altering a predetermined endogenous DNA sequence in the cell.

Abstract: A method of reducing immune response to a viral vector containing a selected transgene is provided. The method involves co-administration of the viral vector and a selected immune modulator capable of inhibiting the formation of neutralizing antibodies and/or CTL elimination of the vectors upon repeated administration.

Abstract: The invention provides a transgenic mouse that is a model for heart muscle disease and heart failure. Also provided are methods of using the transgenic mouse model to study heart muscle disease and heart failure and conditions and treatments related thereto.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

Abstract: Primordial germ cells are extracted from post blastocyst piorcine embryos such as extracting primordial germ cells from the gonadal ridges of 25-day porcine embryos. The primordial germ cells are cultured in long term culture (over 30 days) resulting in cells which resemble embryonic stem cells in morphology and with respect to maintaining pluripotency. The cells obtained can be maintained for several months in culture and can be genetically manipulated using homologous recombination technology in order to insert desired genetic material into the genetic complement of the cell at a desired location. The genetically manipulated cell can be inserted into a porcine blastocyst to produce a chimeric porcine.

Abstract: The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which treat nervous system disease, and a method of treating such disease.

Abstract: Therapeutic methods for the treatment of prostate cancer are described. The methods include a gene therapy method for prostate cancer using the BRCA family of genes, including the BRCA1 and BRCA2 genes. The BRCA family of gene products inhibit the growth and tumorigenesis of prostate cancer cells. Therapeutic methods using the BRCA family of gene products are also described.

Abstract: Transgenic cells, transgenic mice having an Ikaros transgene and methods for the use thereof.

Abstract: In accordance with the present invention, there are provided CRF overproducing transgenic mice which exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. The transgenic mice of the present invention represent a genetic model of CRF overproduction, providing a valuable tool for investigating the long term effects of CRF excess and dysregulation in the central nervous system.

Abstract: NAIP and IAP polypeptides prevent neuronal cell death caused by ischemia, neurodegenerative conditions, and axotomy. The invention provides methods for neuroprotection by the prevention of cell death and kits and methods for the identification of neuroprotective therapeutic compounds.

Abstract: The present invention relates to nucleic acid sequences encoding intracellular binding proteins. More particularly, the nucleic acid comprises a gene coding for an intracellular single chain antibody specific for a ras oncogene under the control of a promoter, the antibody is functional in mammalian cells, and inhibits the transformation of cells that express a ras oncogene.

Abstract: A targeted disruption of the NF1 gene in mice has been used to demonstrate that both neural crest- and placode-derived sensory neurons isolated from NF1(-/-) embryos develop, extend neurites, and survive in the absence of neurotrophins, whereas their wild-type counterparts die rapidly unless NGF or BDNF is added to the culture medium. Moreover, NF1 mutant sympathetic neurons survive for extended periods and acquire mature morphology in the presence of NGF-blocking antibodies. The discovery is useful in screening candidate substances for inhibition of neurofibromin action and in therapy for neurodegeneration due to disease or trauma.

Abstract: The invention provides transgenic animals comprising a lentiviral transgene, such as an HIV transgene. Also within the scope of the invention are cells and eggs from the transgenic animal. Further included are methods for identifying therapeutic compounds for preventing lentiviral infection and treating associated disease (e.g. AIDS).

Abstract: The invention provides a cells which express a gene or genes, derived from the adenovirus E3 region, which block allograft rejection. One class of genes blocks the intracellular transport and/or intracellular maturation within the cells of proteins called MHC class I products. Without limitation as to theory, it is believed that blocking the appearance of this class of proteins on the transplanted cell's surface, prevents the host's immune system from rejecting the graft. Another class of proteins acts to permit TNF .alpha.-mediated cell cytolysis. In one embodiment, the invention is directed towards engrafting the cells that secrete insulin, which are called alternatively, pancreatic .beta.-cells and islet cells, and thereby provide a treatment of diabetes mellitus.

Abstract: The present invention provides for a recombinant insect larvae and a process of manufacturing proteins utilizing insect larvae that allows for the selection of individual larvae for harvest at the point of their optimal expression of a protein of interest. This invention also provides for a process to manufacture proteins in larvae that does not require synchronization of the infection, growth and harvest larvae to optimally manufacture a protein of interest. The invention further provides for a process of producing interleukin-2 in larvae.

Abstract: An erythropoietin-inducible, erythroid-specific DNA construct is disclosed. The DNA construct comprises a promoter sequence from a sheep juvenile beta globin gene, an erythroid-specific enhancer sequence from the locus control region of the human beta globin gene and a nucleotide coding sequence of interest.

Abstract: The invention relates to an isolated DNAc molecule comprising a promoter P and an L1 cassette sequence comprising a core L1 retrotransposon element and methods of use thereof.

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

Abstract: A composition comprising genetically altered human neutrophil precursor cells, wherein the cellular component is comprised of at least about 16% human myeloblasts and promyelocytes, which have been derived from neutrophil progenitor cells obtained from peripheral blood, bone marrow or cord blood, and less than about 5% colony forming units (CFU) of at least about 50 cells is provided. An alternative composition comprising genetically altered human neutrophil precursor cells, wherein the cellular component is comprised of at least about 16% CD15+CD11b- cells and less than about 5% colony forming units (CFU) of at least about 50 cells also is provided, wherein at least about 60% of the CD15+CD11b- cells are myeloblasts and promyelocytes.

Abstract: Described herein is an isolated polynucleotide encoding an LPA receptor. Also described is a recombinant DNA molecule comprising a nucleic acid encoding an LPA receptor and expression controlling elements linked therewith, as well as the use of nucleic acid coding for an LPA receptor for expression to obtain a functional receptor protein and for further gene cloning to identify structurally related receptor proteins. Also described herein is LPA receptor as a product of recombinant production in a cellular host. Described is a method of utilizing the LPA receptor in a chemical screening program to identify LPA receptor ligands. The invention further describes antibodies directed to the LPA receptor for use for example in diagnosis of conditions wherein the levels of LPA are altered.