Abstract: The present invention relates to methods of therapeutic or prophylactic treatment of connective tissue diseases by systemic or local delivery of a nucleic acid sequence to a mammalian host. Expression of the nucleic acid sequence results in the systemic delivery of a biologically active protein or peptide which acts to antagonize inflammatory, hypertrophic and erosive phenomenon associated with connective tissue disease. Systemic delivery of such gene products results in sustained treatment of connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus.

Abstract: The present invention provides methods and compositions for enhancing channel activity to the mutant cystic fibrosis trans-membrane conductance regulator protein (CFTR). The compositions of the invention comprise polypeptides containing CFTR sub-domains that are designed to mimic the folding defect of the full length mutant CFTR proteins, resulting in competitive binding to cytoplasmic chaperones such as Hsc/Hsp7O and Hdj2. The methods of the invention comprise transduction, or recombinant expression, of CFTR polypeptides in a cell expressing mutant CFTR. The presence of the CFTR polypeptide results in a dominant effect whereby the CFTR polypeptide competes with the endogenously expressed mutant CFTR for binding to cytoplasmic chaperones such as Hsc/Hsp70 and Hdj2. Mutant CFTR proteins include, but are not limited to, &Dgr;F508 CFTR.

Abstract: The present invention relates to internalizing peptides which facilitate the uptake and transport of cargo into the cytoplasm and nuclei of cells as well as methods for the identification of such peptides. The internalizing peptides of the present invention are selected for their ability to efficiently internalize cargo into a wide variety of cell types both in vivo and in vitro. The method for identification of the internalizing peptides of the present invention comprises incubating a target cell with a peptide display library, isolating peptides with internalization characteristics and determining the ability of said peptide to internalize cargo into a cell.

Abstract: Methods for treating a connective tissue disorder by introducing at least one gene encoding a product into at least one target cell of a mammalian host for use in treating the mammalian host are disclosed. These methods include employing recombinant techniques to produce a vector molecule containing the DNA sequence encoding for the product and infecting the target cell of the mammalian host using the vector. The injection can be done in vivo, by directly injecting the vector into the host, or can be done in vitro by transfecting a population of cultured target cells with the vector and transplanting them each into the host. Nonviral means can also be used to introduce the DNA sequence to the host. Administration of more than one gene of interest results in an enhanced therapeutic benefit.

Abstract: The present invention relates to internalizing peptides which facilitate the uptake and transport of cargo into the cytoplasm and nuclei of cells as well as methods for the identification of such peptides. The internalizing peptides of the present invention are selected for their ability to efficiently internalize cargo into a wide variety of cell types both in vivo and in vitro. The method for identification of the internalizing peptides of the present invention comprises incubating a target cell with a peptide display library, isolating peptides with internalization characteristics and determining the ability of said peptide to internalize cargo into a cell.

Abstract: Methods for introducing at least one gene encoding a product into at least one target cell of a mammalian host for use in treating the mammalian host are disclosed. These methods include employing recombinant techniques to produce a vector molecule that contains the gene encoding for the product, and infecting the target cells of the mammalian host using the DNA vector molecule. A method to produce an animal model for the study of connective tissue pathology is also disclosed.

Abstract: The subject invention concerns a method of introducing at least one DNA sequence expressing a protein or protein fragment which substantially alleviates articular cartilage defects. This method involves in vitro culture of chondrocytes, transfection of the chondrocytes with a recombinant vector housing the DNA sequence to be expressed, and delivery of the transfected chondrocytes to the damaged cartilage region. This method can also be used in tandem with synovial cell delivery techniques of the present invention. This method is also useful as a model in animal studies regarding joint pathologies.

Abstract: The present invention relates to methods and compositions for inhibiting pancreatic &bgr; cell dysfunction and Fas-mediated apoptosis. The invention relates to recombinant vectors, including viral vectors, comprising nucleic acids molecules encoding inhibitors of interleukin-1&bgr; (IL-1&bgr;) and Fas-mediated apoptosis and the use of such vectors for transfer of said nucleic acid molecules into &bgr; cells. The invention encompasses genetically engineered &bgr; cells comprising nucleic acid molecules encoding inhibitors of IL-1&bgr; signal transduction. The invention further relates to methods for transplanting such genetically engineered &bgr; cells into a host recipient with a pancreatic disorder. The methods and compositions of the invention may be used to reduce Il-1&bgr; mediated &bgr; cell dysfunction and apoptosis, thereby reducing the insulitis associated with pancreatic disorders such as insulin dependent diabetes mellitus (IDDM).

Abstract: Methods for transferring a gene to an intervertebral disc are disclosed. Such methods find application in the treatment of patients for degenerative disc disorders, by use of a gene encoding a product that imparts a therapeutic and/or prophylactic benefit. The present methods also find application in the establishment of an animal model for the study of degenerative disc disease. A genetically modified intervertebral disc cell is also disclosed.

Abstract: The subject invention concerns a method of introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host for use in treating the mammalian host including employing recombinant techniques to produce a DNA vector molecule which contains the gene encoding for the product and infecting the connective cell of the mammalian host using the DNA vector molecule using the gene coding for the product. A method is provided for introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host employing non-viral methods. A method to produce an animal model for the study of connective tissue pathology is also disclosed. Additionally, this invention provides a method of using in vivo a gene encoding and extracellular interleukin-1 binding domain of an interleukin-1 receptor.

Abstract: The present invention provides novel, improved retroviral vectors which can be used for gene therapy, more specifically, retroviral vectors which are not only safer, more versatile, and more convenient than any other existing vectors, but they also drive high levels of gene expression and high viral titer. In retroviral vectors of the present invention, gag and env coding sequences are deleted, and all or part of U3 can be readily substituted with heterologous, non-retroviral promoter elements. Furthermore, at least one internal ribosome entry site is employed to express more than one genes, and multicloning sites are placed in an insertion site for cloning of a heterologous promoter or a foreign gene.

Abstract: Methods for treating a connective tissue disorder by introducing at least one gene encoding a product into at least one target cell of a mammalian host for use in treating the mammalian host are disclosed. These methods include employing recombinant techniques to produce a vector molecule containing the DNA sequence encoding for the product and infecting the target cell of the mammalian host using the vector. The injection can be done in vivo, by directly injecting the vector into the host, or can be done in vitro by transfecting a population of cultured target cells with the vector and transplanting them each into the host. Nonviral means can also be used to introduce the DNA sequence to the host. Administration of more than one gene of interest results in an enhanced therapeutic benefit. Also disclosed is a method for treating a connective tissue disorder by introducing at least one gene encoding a product into at least one target cell of a joint of a host for use in treating multiple joints of the host.

Abstract: Methods for introducing at least one gene encoding a product into at least one target cell of a mammalian host for use in treating the mammalian host are disclosed. These methods include employing recombinant techniques to produce a vector molecule that contains the gene encoding for the product, and infecting the target cells of the mammalian host using the DNA vector molecule. A method to produce an animal model for the study of connective tissue pathology is also disclosed.

Abstract: The subject invention concerns a method of introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host for use in treating the mammalian host including employing recombinant techniques to produce a DNA vector molecule which contains the gene encoding for the product and infecting the connective cell of the mammalian host using the DNA vector molecule using the gene coding for the product. A method is provided for introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host employing non-viral means. In a specific example, isolated synovial cells were infected with a retrovirus comprising a DNA sequence encoding IRAP and the transfected cells administered to an arthritic joint. A method to produce an animal model for the study of connective tissue pathology is also disclosed.

Abstract: The present invention relates to methods of therapeutic or prophylactic treatment of connective tissue diseases by systemic or local delivery of a nucleic acid sequence to a mammalian host. Expression of the nucleic acid sequence results in the systemic delivery of a biologically active protein or peptide which acts to antagonize inflammatory, hypertrophic and erosive phenomenon associated with connective tissue disease. Systemic delivery of such gene products results in sustained treatment of connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus.