Abstract: Methods and compositions for producing a mammal capable of expressing an exogenously supplied gene in cells of the airway are disclosed. Lipid carrier-nucleic acid complexes or nucleic acid abre are prepared then delivered via aerosol or systemically to the lung abre or lung plus extrapulmonary tissues. The invention provides a direct method for transforming pulmonary cells as a means for treating the manifestations of CF in the lung and involved extrapulmonary tissues.

Abstract: The present invention relates to a transcription regulatory region of a myostatin gene. In particular, the invention relates to a 2.5 kb polynucleotide immediately 5′ to the myostatin coding sequence, its nucleotide sequence and methods of using this regulatory region, and fragments thereof. The present invention relates to the use of the myostatin promoter of the present invention to direct expression of a target gene in a tissue specific manner, i.e. muscle tissue. The present invention relates to the use of the myostatin promoter of the present invention in high throughput screens to identify test compounds which inhibit myostatin promoter activity or myostatin expression.

Abstract: The invention provides a method for ameliorating gastrointestinal inflammation, particularly chronic gastrointestinal inflammation such as inflammatory bowel disease (IBD), in a subject. In one embodiment, the method comprises administering an immunomodulatory nucleic acid to a subject suffering from or susceptible to gastrointestinal inflammation.

Abstract: Disclosed are methods and compositions for treatment of diabetes, obesity and diabetic-related conditions. The methods include gene therapy based administration of a therapeutically effective amount of vectors encoding the following: glucokinase regulatory protein alone or co-administered with glucokinase or with metabolism modifying proteins; glucokinase co-administered with metabolism modifying proteins; or glucokinase regulatory protein co-administered with glucokinase in combination with metabolism modifying proteins, to a diabetic patient. Wherein the metabolism modifying proteins include UCP2, UCP3, PPAR&agr;, OB-Rb, GLP-1 and GLP-1 analogs (administered via vector or directly as a peptide). Preferred examples of GLP-1 analogs include GLP-1-Gly8, Extendin-4 and the “Black Widow” chimeric GLP-1 analog. Additionally, PPAR&agr; ligands and DPP-IV inhibitors may be co-administered with the above.

Abstract: The present invention provides a human gene sequence that encodes the CDDP-1 polypeptide, which is involved in cell differentiation, in particular differentiation of undifferentiated progenitor cells into neutrophils, monocytes/macrophages, mast cells, and/or erythroid cells. Assays for detecting CDDP-1 expression, vectors that express CDDP-1, methods for using CDDP-1 to induce or promote cell differentiation, and transgenic animals deficient in one or both CDDP-1 alleles are described.

Abstract: Methods of inhibiting vascular smooth muscle cell proliferation and preventing restenosis by transducing the vascular smooth muscle cells with a viral veactor expressing RB2/p130 are provided.

Abstract: The present invention relates to a graft animal model for propagating papilloma virus and for evaluating and testing candidate therapeutic agents against papilloma virus. The animal model comprises, a recipient animal engrafted with injured skin graft infected with a host-specific papilloma virus (PV). The grafted skin, having demonstrable papillomas supports the propagation of its host-specific PV. The invention particularly relates to a xenograft animal model for hosting and propagating human papillomavirus (HPV), thereby providing a means for generating infectious and passaging HPV suspensions, and for screening candidate therapeutic agents against HPV. The invention additionally relates to a novel method for generating the xenograft human animal model.

Abstract: The present invention provides mutants of the Rb and p53 genes and methods utilizing these mutants therapeutically. Along with mutated Rb genes and p53 genes, the present invention provides mutated Rb and p53 proteins and plasmids containing a mutated Rb gene or a p53 gene. In addition, the present invention provides cells transfected with the plasmids of the present invention. Moreover, the present invention provides for methods of treating a variety of pathophysiological cell proliferative diseases.

Abstract: The present invention relates to a novel VEGF protein product, and nucleic acid encoding the novel protein product, comprising exons 1-6 and 8 of the VEGF gene, and its use thereof in treating the cardiovascular system and its diseases through effects on anatomy, conduit function, and permeability. VEGF145 has been found to be an active mitogen for vascular endothelial cells and to function as an angiogenic factor in-vivo. VEGF145 has novel properties compared with previously characterized VEGF species with respect to cellular distribution, susceptibility to oxidative damage, and extra-cellular matrix (ECM) binding ability. The present invention provides methods of treating the cardiovascular system, enhancing endothelialization of diseased vessels, and enhancing drug permeation by providing the novel VEGF protein product. The invention also provides expression vectors, compositions, and kits for use in the methods of the invention.

Abstract: Methods of promoting tolerance and inhibiting NK cell mediated attack in a human recipient to a swine graft are disclosed The methods include introducing into the recipient a swine hematopoietic stem cell which has been transformed with a transgene encoding a human MHC class I protein that inhibits recipient NK cell mediated attack.

Abstract: Methods and compositions for treating diabetes mellitus in a patient in need thereof are provided. The methods include administering to a patient a composition providing a gastrin/CCK receptor ligand, e.g., a gastrin, and/or an epidermal growth factor (EGF) receptor ligand, e.g., TGF-&agr;, in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g., a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g., a TGF-&agr; gene. The methods also include transplanting into a patient cultured pancreatic islets in which mature insulin-secreting beta cells are proliferated by exposure to a gastrin/CCK receptor ligand and an EGF receptor ligand.

Abstract: A method of transplanting a transplant derived from a donor into a recipient is disclosed. The method comprises the steps of (a) transplanting the transplant into the recipient; and (b) administering to the recipient a dose including non-alloreactive anti-third party cytotoxic T-lymphocytes (CTLs), wherein the non-alloreactive anti-third party CTLs are generated by directing T-lymphocytes of the donor against a third party antigen or antigens, the dose is substantially depleted of T-lymphocytes capable of developing into alloreactive CTLs, thereby preventing or ameliorating both graft rejection by the recipient and graft versus host disease.

Abstract: A method of inducing resistance to or regression of tumor growth comprising placing tumor cells in culture in vitro or ex vivo supplemented with a pro-apoptotic agent for a period of time, transferring the tumor cells into a diffusion chamber, thereby producing a cell-containing chamber, inserting the chamber into a human for a therapeutically effective time, thereby inducing resistance to or regression of tumor growth.

Abstract: The present invention relates to nucleic acid vaccines encoding multiple CTL and HTL epitopes and MHC targeting sequences.

Abstract: The use of recombinant adeno-associated virus (AAV) virions for the treatment of solid tumors is disclosed. The invention provides for the use of recombinant AAV virions to deliver an AAV vector containing a drug-susceptibility gene and a second gene capable of providing an ancillary effect to solid tumor cells. The second gene can be used to enhance the immunogenicity of the transduced tumor cell. Alternatively, the second gene can be used to provide a tumorstatic effect. The invention also provides for the use of recombinant AAV virions to deliver an interferon gene, or a tumor suppressor gene to provide a therapeutic effect in a transduced tumor cell.

Abstract: The invention concerns the use of a eukaryotic cell coding for at least an HLA-G isoform, to obtain an immunomodulating medicine for inhibiting the activity of killer cells, in particular NK cells and/or for inhibiting the primary allogenic response, in parthologies or situations in which the killer cells are activated or for preparing a medicine to raise the inhibiting function of the isoform(s) expressed by said cells with respect to killer cells, in particular NK cells, in pathologies where these killer cells are inhibited by the molecule of the major histocompatibility complex of I HLA-G classes. The invention also concerns eukaryotic cells expressing at their surface at least an HLA-G isoform and their applications. The invention further concerns transgenic animals specifically expressing at least an HLA-G isoform.

Abstract: Disclosed is a method for enhancing an immune response to a substance, such as an antigen or microbial pathogen. The immune response can be, for example, production of IgG2 antibodies. The method comprises administering an immunostimulatory nucleotide sequence (ISS) to a subject at least one hour prior to exposure to the substance by the subject. The subject may be exposed to the substance either naturally, as with an environmental pathogen, or by administration, as with a known antigen. The method can be used for protecting or immunizing a subject against an antigen or pathogen, providing more effective immunization than if the ISS were co-administered with the substance. The method can be used prophylactically or therapeutically. In preferred embodiments, the ISS comprises a CG, p(GC) or p(IC) DNA or RNA nucleotide sequence. Of these, a CG containing nucleotide sequence is preferred. The ISS can further comprise a pG nucleotide sequence.

Abstract: A method of inducing resistance to tumor growth comprising placing tumor cells in culture in vitro supplemented with a pro-apoptotic agent for a period of time, transferring the tumor cells into a diffusion chamber, thereby producing a cell-containing chamber, inserting the chamber into a mammal for a therapeutically effective time, thereby inducing resistance to tumor growth. The pro-apoptotic agents include nucleic acid molecules, proteins or peptides, non-proteins or non-polynucleotide compounds, and a physical conditions.

Abstract: The present invention relates to a fusion protein comprising a first amino acid sequence comprising the sequence of the C-terminal 40 amino acids of bovine IF1 ATPase inhibitor protein, and a second amino acid sequence not naturally associated with the first region. The invention further relates to methods for preparing an immunoglobulin comprising immunizing an animal with the fusion protein and recovering immunoglobulin specific for a region of the fusion protein.