Abstract: A method to increase the efficiency of transduction of hematopoietic and other cells by retroviruses includes infecting the cells in the presence of fibronectin or fibronectin fragments. The fibronectin and fibronectin fragments significantly enhance retroviral-mediated gene transfer into the cells, particularly hematopoietic cells including committed progenitors and primitive hematopoietic stem cells. The invention also provides improved methods for somatic gene therapy capitalizing on enhanced gene transfer, hematopoietic cellular populations, and novel constructs for enhancing retroviral-mediated DNA transfer into cells and their use.

Abstract: A method is described for the rapid identification and isolation of cells based on the presence or absence of an ectopically-expressed N-acetyllactosaminide 3-? Galactosyltransferase (?GT) enzyme for the production of ?Galactosyl-(1,3)Galactosyl (?Gal) epitopes on the surface of ?Gal-negative cells. These cells which are genetically modified to express the ?GT enzyme and ?Gal epitopes on glycosylated lipids and proteins of the cell surface are then labeled via an antibody composition which recognizes and binds the ?Gal epitopes on the cell surface. Cells labeled with the anti-?Gal antibody can be isolated by sorting via fluorescence activated cell sorting (FACS), or by magnetic panning techniques. This method is suitable for the rapid positive or negative selection of ?Gal-positive cells from within a population of ?Gal-negative cells without the need to expose cells to antibiotics for any period of time.

Abstract: The invention relates to methods and products for deregulating gene transcription in neurodegenerative disease associated with an expanded polyglutamine tract in mutant proteins. The invention is useful for preventing and treating diseases associated with expanded polyglutamine tracts, including Huntington's disease. The methods and compositions of the invention are also useful for identifying additional pharmaceutical agents for preventing and treating diseases associated with expanded polyglutamine tracts.

Abstract: The present invention is directed to isolated nucleic acid molecules that encode LIM mineralization protein, or LMP. The invention further provides vectors comprising splice variants of nucleotide sequences that encode LMP, as well as host cells comprising those vectors. Moreover, the present invention relates to methods of inducing bone formation by transfecting osteogenic precursor cells with an isolated nucleic acid molecule comprising a nucleotide sequence encoding splice variants of LIM mineralization protein. The transfection may occur ex vivo or in vivo by direct injection of virus or naked plasmid DNA. In a particular embodiment, the invention provides a method of fusing a spine by transfecting osteogenic precursor cells with an isolated nucleic acid molecule having a nucleotide sequence encoding LIM mineralization protein, admixing the transfected osteogenic precursor cells with a matrix and contacting the matrix with the spine.

Abstract: The invention refers to the production of recombinant gene products from cultures of the yeast Zygosaccharomyces bailii strains transformed with expression vectors bearing the gene coding for said proteins.

Abstract: The present invention provides polypeptides comprising an immunogenic epitope of a M. vaccae protein, polynucleotides encoding such polypeptides, and fusion proteins comprising at least one such polypeptide, together with genetic constructs comprising at least one inventive polynucleotide. Compositions comprising such polypeptides, polynucleotides, fusion proteins and/or genetic constructs may be employed in the treatment of infectious diseases and immune disorders.

Abstract: The present invention relates to methods of inducing neuronal production in the brain, recruiting neurons to the brain, and treating a neurodegenerative condition by providing a nucleic acid construct encoding a neurotrophic factor, and injecting the nucleic acid construct intraventricularly into a subject's brain.

Abstract: Disclosed is a developmental animal model of temporal lobe epilepsy and other seizure-related disorders. In particular, the invention provides a method of inducing a permanent change in the neurological development of a rodent, such as a rat, comprising daily administration of low doses of a kainate receptor agonist to the animal in the second postnatal week, wherein after treatment with the kainate receptor agonist the animal exhibits reproducible seizure-like symptoms when exposed to mild to moderate stressors. Rats treated using the above method are particularly useful as a non-human system for studying temporal lobe epilepsy, as well as for studying the efficacy of potential anti-epileptic compounds and pharmaceutical preparations.

Abstract: The present invention is directed towards a method of regulating smooth muscle tone, comprising the introduction, into smooth muscle cells of a subject, of a DNA sequence encoding a protein involved in the regulation of smooth muscle tone, and expression of the DNA sequence in a sufficient number of smooth muscle cells of the subject to regulate smooth muscle tone in the subject. Specifically, the invention provides methods of gene therapy for treating erectile dysfunction, bladder dysfunction, and other smooth muscle disorders. The present invention also provides recombinant viral and non-viral vectors comprising DNA encoding a protein involved in the regulation of smooth muscle tone. Further provided by the present invention is a smooth muscle cell which expresses a gene encoding a protein involved in the regulation of smooth muscle tone.

Abstract: The present invention relates to a composition and method for delivery of biological material, especially nucleic acids into target cells and into the nucleus.

Abstract: The present invention provides novel expression vectors which permit tight regulation of gene expression in eucaryotic cells. More specifically, the invention provides DNA vectors comprising nucleotide sequences that are transcribed to form RNA molecules which are then replicated by a temperature-sensitive replicase to form additional RNA molecules. The RNA molecules produced by replication contain a nucleotide sequence which may be translated to produce a protein of interest or which encode one or more untranslated RNA molecules. Also provided are methods for producing heterologous proteins and untranslated RNA molecules. Further provided are methods for administering heterologous proteins and untranslated RNA molecules to individuals. In addition, pharmaceutical compositions are provided comprising the DNA and RNA molecules of the invention and a pharmaceutically acceptable carrier.

Abstract: A method for preventing, delaying the onset of or treating diabetes in a patient comprising selecting a patient who is susceptible to developing diabetes, who is developing diabetes or who is diabetic and administering to the patient one or more than one dose of a pharmaceutical agent comprising a polynucleotide encoding a secreted exogenous protein, such as a secreted luciferase or a secreted form of human glutamic acid decarboxylase.

Abstract: The invention relates to novel degradation resistant FGF-1, and methods for producing and using the same. More specifically, the invention relates to identification of a thrombin degradation resistant FGF-1, an a nucleic acid encoding the same. The thrombin degradation resistant FGF-1 can elicit responses that are otherwise typically impeded by degradation of FGF-1 by thrombin. Thrombin degradation resistant FGF-1 is an important molecule for effecting an FGF-1 response that would be otherwise inhibited by thrombin. Thus, the present invention provides a powerful therapeutic for diseases or disorders wherein an FGF-1 response can mediate a reduction in the frequency or intensity of a symptom of the disease or disorder but for degradation of FGF-1 before it can effect the response.

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. Methods of generating mutations in genes of interest and of making various cells mismatch repair defective through the use of chemicals to block mismatch repair in in vivo are disclosed.

Abstract: D type CpG oligodeoxynucleotides are provided herein that include a sequence represented by the following formula: 5?X1X2X3Pu1 Py2 CpG Pu3 Py4 X4X5X6(W)M(G)N-3? wherein the central CpG motif is unmethylated, Pu is a purine nucleotide, Py is a pyrimidine nucleotide, X and W are any nucleotide, M is any integer from 0 to 10, and N is any integer from 4 to 10. Methods of using these oligodeoxynucleotides to induce an immune response are provided.

Abstract: The present invention provides a human tumor suppressor protein having the amino acid sequence of SEQ ID NO: 2; a polynucleotide encoding the tumor suppressor protein; an expression vector containing the polynucleotide; a microorganism or animal cell transformed with the expression vector; a method for suppressing proliferation of a cancer cell which comprises introducing the expression vector into a cancer cell to induce apoptosis thereof; and a pharmaceutical composition for preventing or treating cancer which comprises a therapeutically effective amount of the polynucleotide and a pharmaceutically acceptable carrier.

Abstract: In accordance with the present invention, it has been discovered that CREB regulates hepatic gluconeogenesis via the co-activator, PGC-1. PGC-1 potentiated glucocorticoid induction of the gene for PEPCK, the rate limiting enzyme in gluconeogenesis, via the glucocorticoid response unit in the promoter, indicating that activation of PGC-1 by CREB in liver contributes to the pathogenesis of diabetes mellitus. In accordance with the above discoveries, the present invention provides a method of identifying a compound that modulates gluconeogenesis. The invention method comprises contacting CREB and a nucleic acid comprising a PGC-1 promoter with a test compound, and determining if the test compound modulates binding between CREB and the PGC-1 promoter.

Abstract: Methods of treating patients who are suffering from a disease, disorder or condition characterized by a bone cartilage or lung defect are disclosed. The methods comprising the step of intravenous administration of stromal cells isolated from normal syngeneic individuals or intravenous administration of stromal cells isolated from the patient subsequent to correction of the genetic defect in the isolated cells. Implant devices comprising a container that has at least one membrane surface and stromal cells isolated from bone marrow that comprise a gene construct are disclosed. The gene construct in the stromal cells comprises a nucleotide sequence that encodes a beneficial protein operably linked to regulatory elements which function in stromal cells. Methods of treating individuals with diseases, disorders or conditions which can be treated with a beneficial protein, including diseases, disorders or conditions characterized by gene defects are disclosed.

Abstract: The invention relates to a recombinant vector for the cloning and/or expression and/or transfer of an exogenous nucleotide sequence characterized in that it consists of any sequence contained in the ClaI-PvuII fragment comprising nucleotides 7702 to 1527 (SEQ ID NO: 11) of the sequence given in FIGS. 1A-1D and comprising the LTR sequence included between nucleotides 7842 and 144, the PBS site starting at nucleotides 145, the packaging sequence included in the sequences of 250 nucleotides following the end of the LTR sequence, the said sequence being capable of controlling the cloning and/or expression and/or transfer at the exogenous sequence whatever its transcriptional orientation with respect to the transcriptional orientation of the virus. It relates to the use of this vector for the transfer and/or cloning and/or expression of genes, in particular in the context of gene therapy.

Abstract: Compositions for targeting expression of a gene such as an antitumor gene may contain a first nucleic acid construct in which expression of a first gene is controlled by a first promoter whose function is suppressed in non-tumor cells, and a second nucleic acid construct in which expression of a second gene for down-regulating the first gene in non-tumor cells is controlled by a second promoter that is up-regulated in non-tumor cells. The second promoter may be regulated by means of p53 binding, targeting expression of the first gene to cells in which p53 down-regulation of expression is disrupted, e.g. cells in which p53 is mutated. The first promoter may be one which is unregulated in tumor cells, for example the Hsp70 promoter which is upregulated in mutant p53 tumor cells. A suitable antitumor agent in thymidine kinase.