Abstract: A multicellular in vitro assay which models the combined stages of angiogenesis is disclosed. The assay permits the evaluation of drug candidates for their potential utility in treating pathological conditions such as chronic dermal ulcers, tumors, diabetic retinopathy, psoriasis and inflammation.

Abstract: This invention provides isolated nucleic acids encoding mammalian SNORF25 receptors, purified mammalian SNORF25 receptors, vectors comprising nucleic acid encoding mammalian SNORF25 receptors, cells comprising such vectors, antibodies directed to mammalian SNORF25 receptors, nucleic acid probes useful for detecting nucleic acid encoding mammalian SNORF25 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding mammalian SNORF25 receptors, transgenic, nonhuman animals which express DNA encoding normal or mutant mammalian SNORF25 receptors, methods of isolating mammalian SNORF25 receptors, methods of treating an abnormality that is linked to the activity of the mammalian SNORF25 receptors, as well as methods of determining binding of compounds to mammalian SNORF25 receptors, methods of identifying agonists and antagonists of SNORF25 receptors, and agonists and antagonists so identified.

Abstract: The present invention provides a human polypeptide homolog of human tankyrase protein (THP) and polynucleotides which identify and encode THP. In addition, the invention provides expression vectors, host cells and methods for its production. The invention also provides methods for the identification of THP agonists/antagonists, useful for the treatment of human diseases, such as human cancer and age related diseases.

Abstract: A truncated mammalian growth factor, displaying homology to both basic and acidic fibroblast growth factor in a single polypeptide, is disclosed herein. The growth factor is substantially smaller (i.e. has fewer amino acid residues) than the full-length mammalian growth factor, has a higher affinity for fibroblast growth factor receptors than full-length K-FGF and basic fibroblast growth factor and increased mitogenic activity. Also disclosed herein are DNA sequences encoding the truncated growth factor, pharmaceutical formulations containing the truncated growth factor and methods to heal burns and wounds in a mammal by administering the pharmaceutical formulations.

Abstract: A genetically-engineered anaerobic organism is provided which, under anaerobic conditions present in a solid tumor, produces an enzyme capable of catalyzing the conversion of a prodrug to its highly cytotoxic product in situ and methods of treating tumors using same.

Abstract: This invention provides a mammalian cell useful for retroviral packaging comprising two plasmids, both of which comprise the 5′ long terminal repeat (LTR) sequence from a helper virus, neither of which comprise a functional &psgr; packaging sequence or a 3′ LTR from the helper virus, one of which comprises the env gene from the helper virus and the other of which comprises the gag and pol genes from the helper virus. This invention also provides a process for preparing a producer cell useful for transferring a foreign gene into a mammalian cell which comprises treating the above-described mammalian cell with a vector plasmid so as to insert the vector plasmid into the cell and thus create the producer cell, the vector plasmid comprising the foreign gene, a functional &psgr; packaging sequence from the helper virus, both the 5′ and 3′ LTRS from the helper virus, and a gene encoding a selectable or identifiable phenotypic trait, and recovering the producer cell so created.

Abstract: The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumor progression in cells involved in human tumors such as melanomas, breast, gastrointestinal, lung, and bone tumors, various types of skin cancers, and other neoplastic conditions such as leukemias and lymphomas. Genes are identified that are differentially expressed in benign (e.g., non-malignant) tumor cells relative to malignant tumor cells exhibiting a high metastatic potential. Genes are also identified via the ability of their gene products to interact with gene products involved in the progression to, and/or aggressiveness of, neoplastic tumor disease states. The genes and gene products identified can be used diagnostically or for therapeutic intervention.

Abstract: Bacterial, yeast and animal cells and methods for overexpressing recombinant heparanase in cellular systems, methods of purifying recombinant heparanase therefrom and modified heparanase species which serve as precursors for generating highly active heparanase by proteolysis.

Abstract: A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) and with concanavalin A on transplantation to subjects suffering of myopathy like muscular dystrophy is disclosed and claimed. Recipient muscles show a higher percentage of functional cells, a four-fold increase, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. The recipient subjects were immunosuppressed with FK 506. When growing myoblasts with 20 &mgr;g/ml concanavalin A or 100 ng/ml TPA for two to four days, migration of donor cells in recipient tissue was increased by 3-4 fold.

Abstract: Retroviral vectors which are resistant to inactivation by human serum. The retroviral vectors are produced in a cell line which is resistant to lysis by human serum, such cell lines including the HOS, Mv-1-Lu, HT1080, TE671, and human 293 cell lines, as well as cell lines derived therefrom. Such retroviral vectors are especially useful as in vivo gene delivery vehicles.

Abstract: This invention provides an isolated nucleic acid encoding a mammalian galanin receptor, an isolated galanin receptor protein, vectors comprising isolated nucleic acid encoding a mammalian galanin receptor, cells comprising such vectors, antibodies directed to a mammalian galanin receptor, nucleic acid probes useful for detecting nucleic acid encoding a mammalian galanin receptor, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding a mammalian galanin receptor, nonhuman transgenic animals which express DNA encoding a normal or a mutant mammalian galanin receptor, as well as methods of determining binding of compounds to mammalian galanin receptors.

Abstract: A combination of adenoviral and retroviral vectors used to construct second generation packaging cells that deliver marker genes to target cells is described. A vector based upon Moloney murine leukemia virus (MLV) was used to deliver marker genes, and an adenovirus-based delivery system was used to deliver MLV structural genes (gagpol and env) to cultured cells. The procedure transformed the cells into new retroviral producer cells, which generate replication-incompetent retroviral particles in the culture supernatant for transferring marker genes to target cells. The titer of the retroviral-containing supernatant generated from the second generation producer cells reached above 105 cfu/ml which is comparable to the MLV-based producer cell lines currently used in human gene therapy trials. The vector and procedures are adaptable for experimental human gene therapy in which the new producer cells are transplanted into patients for continuous gene transfer.

Abstract: This invention provides an isolated nucleic acid molecule encoding a mammalian 5-HT4B receptor and an isolated nucleic acid molecule encoding a human 5-HT4B receptor, an isolated protein which is mammalian 5-HT4B receptor, vectors comprising an isolated nucleic acid molecule encoding a mammalian 5-HT4B receptor, vectors comprising an isolated nucleic acid molecule encoding a human 5-HT4B receptor, mammalian cells comprising such vectors, antibodies directed to the 5-HT4B receptor, nucleic acid probes useful for detecting nucleic acid encoding a mammalian or human 5-HT4B receptor, antisense oligonucleotides complementary to any sequences of a nucleic acid molecule which encodes a mammalian or human 5-HT4B receptor, pharmaceutical compounds related to the human 5-HT4B receptor. This invention further provides methods for determining ligand binding, detecting expression, drug screening, and treatments for alleviating abnormalities associated with a human 5-HT4B receptor.

Abstract: Provided herein are methods and devices for inducing the formation of functional replacement nonarticular cartilage tissues and ligament tissues. These methods and devices involve the use of osteogenic proteins, and are useful in repairing defects in the larynx, trachea, interarticular menisci, intervertebral discs, ear, nose, ribs and other fibrocartilaginous tissues in a mammal.

Abstract: This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors.

Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: Provided by the invention are novel methods, vectors and cells for the recombinant production of desired gene products. In particular, the invention relates to increased production of desired gene products by inducibly arresting cell proliferation. The invention also provides novel multicistronic expression vectors that are useful not only for recombinant gene expression, but also for other applications such as gene therapy, tissue engineering and metabolic engineering.

Abstract: This invention provides viral and retroviral vectors which comprises a nucleic acid molecule encoding a human cytosolic aldehyde dehydrogenase or a glutamylcysteine synthetase or combinations thereof. Further, this invention provides an isolated mammalian nucleic acid molecule encoding an cytosolic aldehyde dehydrogenase and glutamylcysteine synthetase. In addition, this invention provides a method for reducing the toxic effects of a cyclophosphamide in a subject which comprises replacing the subject's hematopoietic cells with hematopoietic cells of having the retroviral vector. Further, this invention provides a method for introducing a selectable marker into a mammalian cell which comprises transfecting the cell with a nucleic acid molecule encoding human cytosolic aldehyde dehydrogenase or glutamylcysteine synthetase. Lastly, this invention provides a method for selecting mammalian cells expressing protein of interest which comprises: a).

Abstract: Nucleic acid constructs are disclosed which possess a nuclear retention signal which is linked, downstream in the reading direction, to a transgene. The nuclear retention signal can regulate the presence of the transcription product in the cell nucleus or else the intracellular transport of the transcription product.

Abstract: This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors.

Abstract: This invention provides isolated nucleic acids encoding mammalian SNORF25 receptors, purified mammalian SNORF25 receptors, vectors comprising nucleic acid encoding mammalian SNORF25 receptors, cells comprising such vectors, antibodies directed to mammalian SNORF25 receptors, nucleic acid probes useful for detecting nucleic acid encoding mammalian SNORF25 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding mammalian SNORF25 receptors, transgenic, nonhuman animals which express DNA encoding normal or mutant mammalian SNORF25 receptors, methods of isolating mammalian SNORF25 receptors, methods of treating an abnormality that is linked to the activity of the mammalian SNORF25 receptors, as well as methods of determining binding of compounds to mammalian SNORF25 receptors, methods of identifying agonists and antagonists of SNORF25 receptors, and agonists and antagonists so identified.

Abstract: This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors.

Abstract: The present invention relates to a method of gene or DNA targeting in cells of vertebrate, particularly mammalian, origin. That is, it relates to a method of introducing DNA into primary or secondary cells of vertebrate origin through homologous recombination or targeting of the DNA, which is introduced into genomic DNA of the primary or secondary cells at a preselected site. The present invention further relates to primary or secondary cells, referred to as homologously recombinant (HR) primary or secondary cells, produced by the present method and to uses of the homologously recombinant primary or secondary cells. The present invention also relates to a method of turning on a gene present in primary cells, secondary cells or immortalized cells of vertebrate origin, which is normally not expressed in the cells or is not expressed at significant levels in the cells.

Abstract: This invention provides an isolated nucleic acid encoding a mammalian LPA receptor, a purified mammalian LPA receptor, vectors comprising isolated nucleic acid encoding an mammalian LPA receptor, cells comprising such vectors, antibodies directed to a mammalian LPA receptor, nucleic acid probes useful for detecting nucleic acid encoding a mammalian LPA receptor, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding mammalian LPA receptor, transgenic, nonhuman animals which express DNA encoding a normal or a mutant mammalian LPA receptor, methods of isolating an mammalian LPA receptor, methods of treating an abnormality that is linked to the activity of the mammalian LPA receptor, as well as methods of determining binding of compounds to mammalian LPA receptors.

Abstract: An object of the present invention is to provide a protein which induces apoptosis, a base sequence encoding the protein, and an agent for use in the treatment of malignant tumors. The present invention is a protein (ASK1) which has protein kinase activity and enhances SEK1 kinase activity and/or MKK3 kinase activity, or a derivative thereof. Malignant tumors can be treated using the protein according to the present invention or the base sequence encoding the protein.

Abstract: The disclosure describes recombinant alphavirus RNA molecules and expression of heterologous proteins therefrom in animal cells. Recombinant alphaviruses of the present invention, when made to express an antigenic protein, can be administered as vaccines.

Abstract: Method and compositions for regulating cell cycle progression are disclosed. Compositions include nucleic acids comprising a human Cdc5 gene, antisense gene and fragments thereof and a human Cdc5 protein and polypeptide fragments thereof polypeptide. The compositions can be used in a method to treat diseases relating to a cell cycle defect.

Abstract: A novel polypeptide, designated neuronal factor (NF), has been identified by PCR amplification of human genomic DNA. Provided herein is nucleic acid encoding NF useful in diagnostics and in the recombinant preparation of NF. NF is used in the treatment of nerve cells and in diagnostic assays.

Abstract: The invention describes nucleic acids encoding the Daxx protein, including fragments and biologically functional variants thereof. Also included are polypeptides and fragments thereof encoded by such nucleic acids, and antibodies relating thereto. Methods and products for using such nucleic acids and polypeptides also are provided.

Abstract: A polynucleotide molecule useful for stably producing a gene product includes a polynucleotide sequence encoding the gene product (or alternatively a gene transcript) flanked by a 5' sequence and a 3' of an intron. Methods and compositions using this molecule permit enhanced recombinant expression of the gene product and are particularly useful in stabilizing unstable mRNA transcripts, permitting the stable production of desirable genes encoded thereby. Vectors and host cells containing this molecule are useful in the methods.

Abstract: Disclosed test cells are useful for evaluating the carcinogenicity of a compound using a transformation assay. The test cell preferably is transfected with an oncogenic viral recombinant nucleic acid molecule encoding a transforming protein. Cell growth is scored to identify the presence or absence of a transformation characteristic, such as formation of foci, loss of growth factor or serum requirements or anchorage independence. The development of such a transformation characteristic indicates that the compound being tested is carcinogenic.

Abstract: A proteinaceous particle comprises a capsid enveloped by ecotropic Murine Leukemia virus envelope proteins characterized in that a heterologous peptide which binds to a non-murine cell is inserted in, entirely replaces, or replaces a portion of the native Ser-Gly-Gly-Ser-Ser-Pro-Gly of the VRA region of said envelope proteins. A method for preparing a plurality of such proteinaceous particles comprises expressing within a host cell (i) self-assembling capsid proteins, (ii) Murine Leukemia virus envelope proteins, said ENV proteins modified as defined, and optionally, (iii) packageable RNA, and then culturing the host cells and harvesting the resultant budded particles.

Abstract: The present invention provides methods and compositions delivery of agents into the cytoplasm of cells. Particularly, it concerns the use of membrane-penetrating toxin proteins to deliver drugs to the cytoplasm of target cells.

Abstract: The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) that encodes erythropoietin or an insulinotropin (e.g., derivatives of glucagon-like peptide 1 (GLP-1)), methods by which primary and secondary cells are transfected to include exogenous genetic material encoding erythropoietin or an insulinotropin, methods of producing clonal cell strains or heterogenous cell strains that express erythropoietin or an insulinotropin, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells.

Abstract: The present invention relates to methods and compositions for increasing the production of high titre stocks of recombinant AAV (rAAV) through regulation of expression of the AAV REP and CAP proteins. The methods and compositions of the invention are based on the observation that the low level expression of the AAV REP 78/68 protein increases the production of AAV viral capsid protein and efficiency of packaging resulting in production of higher titre recombinant viral stocks. The invention encompasses recombinant AAV vectors that direct the expression of AAV REP and CAP proteins and the use of such vectors for the production of novel stable cell lines capable of generating high titre rAAV vectors. The invention provides methods for regulating the expression of the AAV REP 78/68, REP 40/52 and CAP gene at the transcriptional and post-translational level.

Abstract: The invention provides the promoter of the cdc25B gene, a process for finding cdc25B promoters and methods for using the promoters for preparing a pharmaceutical.

Abstract: This invention provides a method for obtaining a recombinant retroviral packaging cell capable of producing retroviral vectors as well as the recombinant packaging cell obtained by the method. Also provided is a method of producing recombinant retroviral particles obtained by introducing into the packaging cells obtained according to the methods disclosed herein, a recombinant retroviral vector and propagating the resulting producer cells under conditions favorable for the production and secretion of retroviral vector supernatant. The retroviral supernatant produced by these methods also is claimed herein. This invention further provides a method for screening retroviral vector supernatant for high transduction efficiency and methods for producing retroviral vector supernatant for transducing cells with high efficiency in gene therapy applications.

Abstract: A transgenic mouse capable of expressing a reporter gene regulated by human elastin promoter is provided. Mouse fibroblast cultures derived from this transgenic mouse are also provided. In addition, methods of identifying compounds capable of inhibiting cutaneous photodamage with this transgenic mouse or fibroblast cultures derived from these mice are provided.

Abstract: The invention provides a two component system for gene-directed enzyme prodrug therapy which comprises: (a) a vector which encodes a carboxypeptidase which is expressed within a cell; and (b) a prodrug which can be converted into an active drug by said carboxypeptidase, useful in the treatment of tumours.

Abstract: A synthetic antisense oligonucleotide comprising at least seven nucleotides or nucleotide analogues having a sequence complementary to the mRNA sequence of ribonucleotide reductase dimeric protein component R2 including SEQ ID Nos:1-102 is disclosed. A synthetic antisense oligonucleotide comprising at least seven nucleotides or nucleotide analogues having a sequence complementary to the mRNA sequence of ribonucleotide reductase dimeric protein component R1 including SEQ ID Nos:103-161 is also disclosed. The invention also discloses pharmaceutical compositions including the synthetic antisense oligonucleotides of the present invention and methods of using the antisense oligonucleotides to modulation proliferative cells including neoplastic cells.

Abstract: The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes erythropoietin or an insulinotropin [e.g., derivatives of glucagon-like peptide 1(GLP-1)], methods by which primary and secondary cells are transfected to include exogenous genetic material encoding erythropoietin or an insulinotropin, methods of producing clonal cell strains or heterogenous cell strains which express eruthropoietin or an insulinotropin, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells.

Abstract: The invention provides for processes for identifying chemical compounds which specifically bind to a human 5-HT.sub.4B having the amino acid sequence of SEQ ID NO: 2.

Abstract: Methods and compositions are provided for expression of mammalian genes in culture. An amplifiable gene is introduced by homologous recombination in juxtaposition to a target gene, the resulting combination of amplifiable gene and target gene transferred to a convenient host and the target gene amplified by means of the amplifiable gene. The resulting expression host may then be grown in culture with enhanced expression of the target gene.

Abstract: Process and medium for the transfection of higher eukaryotic cells with DNA/polycation complexes, wherein a medium is used which contains ethyleneglycol and/or glycerol. The medium may also contain a substance which prevents the acidification of the endosomes, and/or a lower alcohol such as ethanol. The process is particularly suitable for the transfection of primary cells such as fibroblasts. Stably transformed cells can be obtained thereby, e.g. tumour cells for use as tumour vaccines.

Abstract: Entry of HIV-1 into target cells requires cell surface CD4 as well as additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T cell lines was recently identified and named fusin. Fusin, however, does not promote entry of macrophage-tropic viruses that are believed to be the key pathogenic strains in vivo. It has now been determined that the principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR5, a receptor for the .beta.-chemokines RANTES, MIP-1.alpha., and MIP-1.beta..

Abstract: DNA molecules are disclosed which encode mammalian Cerberus-Like Proteins.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of weight, and to the diagnostic and therapeutic uses to which such modulators may be put. In its broadest aspect, the present invention relates to the elucidation and discovery of nucleotide sequences, and proteins putatively expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight. The nucleotide sequences in object represent the genes corresponding to the murine and human ob gene, that have been postulated to play a critical role in the regulation of body weight and adiposity. Preliminary data, presented herein, suggests that the polypeptide product of the gene in question functions as a hormone.

Abstract: This invention provides a method for obtaining a recombinant retroviral packaging cell capable of producing retroviral vectors and the recombinant packaging cell obtained by the method. Also provided is a method of producing recombinant retroviral particles obtained by introducing into the packaging cells obtained according to the methods disclosed herein, a recombinant retroviral vector and propagating the resulting producer cells under conditions favorable for the production and secretion of retroviral vector supernatant. The retroviral supernatants produced by these methods also is claimed herein. This invention further provides a method for screening retroviral vector supernatant for high transduction efficiency and methods for producing retroviral vector supernatant for transducing cells with high efficiency in gene therapy applications.

Abstract: The present invention pertains to a method for efficiently introducing exogenous genes into primary lymphoid cells without drug selection which comprises the steps (a) deriving a retroviral vector and a helper cell combination that will yield a level of virus production in the range from 5.times.10.sup.6 to 5.times.10.sup.7 units/ml by transfecting a vector into a helper cell followed by selection, isolation of cell clones, and determination of viral titers to identify which virus-producing cell lines produce a virus titer in the range from 5.times.10.sup.6 to 5.times.10.sup.

Abstract: Tumor necrosis factor receptor DNAs and expression vectors encoding TNF receptors, and processes for producing TNF receptors as products of recombinant cell culture, are disclosed.