Abstract: The invention concerns genes involved in the molecular paths for tumor suppression and/or resistance to viruses, and whereof the cell expression is in particular induced or inhibited during apoptosis and/or tumor suppression.

Abstract: The invention provides compositions and methods for muting expression of an endogenous gene in an animal cell, the muting resulting from providing a transgene to a cell. Expression of which transgene is undetectable. The transgene comprises the muting nucleic acid, which is substantially homologous to a portion of the endogenous gene. The portion of the endogenous gene provided on the transgene can be from the 5?-untranscribed end, from the 3? untranscribed end, from an exon or an intron in the coding portion, or from a portion that overlaps any of these portions. Methods are provided for obtaining muting nucleic acid, and for screening for molecules that can mute the gene, and for molecules that can alleviate muting of the gene.

Abstract: A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g.

Abstract: The invention concerns the use of a nucleic acid capable of expressing beta-interferon for the preparation of a pharmaceutical composition for the treatment of an immune disease.

Abstract: This invention relates generally to the field of monitoring production of gene products. In particular, the invention provides methods of monitoring production of a gene product, methods of screening for modulators of production of a gene product, and methods of screening for cellular targets amenable to regulation by a treatment using a plurality of reporter gene systems. The methods described herein find uses in a number of fields such as drug discovery, agricultural or industrial production and environmental monitoring or protection.

Abstract: The field of the invention is activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention relates to expresssing an endogenous gene in a cell at levels higher than those normally found in the cell. Expression of the gene is activated or increased following integration, by non-homolgous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. The method allows the identification and expression of gene undiscovered by current methods since no target sequence is necessary for integration. Thus, gene products associated with human disease and development are obtainable from gene that have not been sequenced and indeed, whose existence is unknown, as well as from well characterized genes. The methods provide gene products from such genes for therapeutic and diagnostic purposes. In one embodiment the vector comprises a promoter, an exon, and an unpaired splice donor sequence, the exon being derived from a eukaryotic gene.

Abstract: The invention encompasses compositions and methods which utilize a cell line comprising a stably integrated recombinant nucleic acid construct comprising: a reporter gene operably linked to a recognition sequence for a sequence-specific DNA-binding protein; and a stably integrated recombinant nucleic acid construct comprising a sequence encoding a fusion protein, the fusion protein comprising a sequence-specific DNA binding domain, wherein the DNA binding domain specifically binds the recognition sequence, and a conditionally active transactivation domain of CHOP, wherein binding of the fusion protein to the recognition sequence results in transactivation of the reporter gene when the transactivation domain fused to the DNA binding domain is activated.

Abstract: A method for inhibiting apoptosis of a cell expressing a death receptor of the TNFR family is disclosed. The method involves treating the cell with a Receptor Internalization and Degradation (RID) protein complex containing RID? (10.4K) and RID? (14.5K) proteins encoded by the E3 region of adenovirus. The cell can be treated by administering to the cell a polynucleotide expressing the RID complex or by administering to the cell a composition containing the RID complex. Compositions containing a RID complex are also disclosed. The compositions and method are useful in the treatment of cancer, degenerative and immune disorders, as well as in promoting survival of tissue transplants. An adenovirus vector for delivering the RID complex to cells is also disclosed.

Abstract: The invention relates to metastasis inducing DNA's, a method of identifying such DNA's and their use in diagnosis and therapy. It includes a method of screening and recovering met-DNA comprising the steps of: (i) transferring fragments of human DNA from malignant, metastatic cancer cells into a cell line that produces only benign, non-metastasizing tumors when injected into a syngeneic animal; (ii) injecting the transformed cells into the syngenic animal; (iii) selecting those animals in which metastasizing tumors have been identified; and (iv) recovering the met-DNA therefrom.

Abstract: The present invention relates to novel promoters, including transcription regulator regions, for the mouse VEGFR-2 receptor, isolated polynucleotides comprising such promoters, nucleic acid constructs comprising such promoters operatively linked to genes encoding a gene product, such as, a reporter, a protein, polypeptide, hormone, ribozyme, or antisense RNA, recombinant cells comprising such nucleic acid constructs, screening for therapeutic drugs using such cells (e.g., screening for compounds that modulate VEGFR-2-mediated angiogenesis), and endothelial tissue-specific gene expression using these novel promoter sequences.

Abstract: A viral or non-viral vector particle having a modified viral surface protein wherein the viral surface protein is modified to include a targeting polypeptide including a binding region which binds to an extracellular matrix component. Such vector particles are useful in delivering genes encoding therapeutic agents to cells located at the site of an exposed extracellular matrix component.

Abstract: The present invention relates to a method for producing plants with improved agronomic and nutritional traits. Such traits include enhanced nitrogen assimilatory and utilization capacities, faster and more vigorous growth, greater vegetative and reproductive yields, and enriched or altered nitrogen content in vegetative and reproductive parts. More particularly, the invention relates to the engineering of plants modified to have altered expression of key enzymes in the nitrogen assimilation and utilization pathways. In one embodiment of the present invention, the desired altered expression is accomplished by engineering the plant for ectopic overexpression of one of more the native or modified nitrogen assimilatory enzymes. The invention also has a number of other embodiments, all of which are disclosed herein.

Abstract: Disclosed are novel isolated nucleic acids and substantially pure protein preparations for naturally occurring and synthetic or chimeric heparan sulfate D-glicosaminyl 3-O-sulfo-transferases (3-OSTs). Also disclosed are uses for these genes and proteins, including uses for the modification and sequencing of glycosaminoglycans.

Abstract: The invention is directed to a purified population of mammalian endothelial, muscle, or neural stem cells. The invention further provides methods for isolating such populations of cells; methods for using such populations of cells for treating mammals; methods for making vectors for gene therapy; and methods for carrying out gene therapy with such vectors.

Abstract: Compositions and methods for the treatment of ophthalmic disorders, particularly preservation of corneal explants and prevention of corneal allograft rejection. These compositions comprise oligonucleotides which are specifically hybridizable with nucleic acids encoding the cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1).

Abstract: Hypersecretion of mucus in the lungs is inhibited by the administration of an epidermal growth factor receptor (EGF-R) antagonist. The EGF-R antagonist may be in the form of a small organic molecule, an antibody, or portion of an antibody that binds to and blocks the EGF receptor. The EGF-R antagonist is preferably administered by injection in an amount sufficient to inhibit formation of goblet cells in pulmonary airways. The degranulation of goblet cells that results in airway mucus production is thereby inhibited. Assays for screening candidate agents that inhibit goblet cell proliferation are also provided.

Abstract: A method for evaluating a test compound's ability to modulate prolyl 4-hydroxylase is disclosed. In one embodiment, the method comprises the steps of introducing a test compound into a test chimeric, P4H-gene modified, or a wild-type nematode, wherein the test chimeric nematode has a complemented prolyl-4-hydroxylase gene mutation, and observing the effect of the test compound on the prolyl 4-hydroxylase activity of the progeny of the test chimeric, P4H-gene modified, or the wild-type nematode, wherein a dpy or embryonic lethal phenotype indicates prolyl-4-hydroxylase inhibition.

Abstract: Methods for isolating CaMK-X1 genes are provided. The CaMK-X1nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as identification of cell type based on expression, and the like.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of hematopoietic cell protein tyrosine kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding hematopoietic cell protein tyrosine kinase. Methods of using these compounds for modulation of hematopoietic cell protein tyrosine kinase expression and for treatment of diseases associated with expression of hematopoietic cell protein tyrosine kinase are provided.

Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. The enhanced rate of mutation can be further augmented using mutagens. Moreover, the hypermutability of mismatch repair deficient cells can be remedied to stabilize cells or mammals with useful mutations.