Abstract: An isolated chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1 is provided. Also provided is an isolated modified chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1. Recombinant expression vectors comprising the chimeric GLP-1 nucleic acid sequences, which produce GLP-1 constitutively are provided, as are human cells transfected with such an expression vector in combination with an expression vector comprising a proinsulin nucleic acid sequence and an expression vector comprising a furin and a glucose-regulatable TGF-alpha promoter. Methods of producing human GLP-1 constitutively are provided as are method of producing GLP-1 and insulin or in a glucose-dependent manner using such transfected cells.

Abstract: An isolated chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1 is provided. Also provided is an isolated modified chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1. Recombinant expression vectors comprising the chimeric GLP-1 nucleic acid sequences, which produce GLP-1 constitutively are provided, as are human cells transfected with such an expression vector in combination with an expression vector comprising a proinsulin nucleic acid sequence and an expression vector comprising a furin and a glucose-regulatable TGF-alpha promoter. Methods of producing human GLP-1 constitutively are provided as are method of producing GLP-1 and insulin or in a glucose-dependent manner using such transfected cells.

Abstract: Methods for maintaining and improving the secretory activity of cells housed in immunoisolation devices.

Abstract: An isolated chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1 is provided. Also provided is an isolated modified chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1. Recombinant expression vectors comprising the chimeric GLP-1 nucleic acid sequences, which produce GLP-1 constitutively are provided, as are human cells transfected with such an expression vector in combination with an expression vector comprising a proinsulin nucleic acid sequence and an expression vector comprising a furin and a glucose-regulatable TGF-alpha promoter. Methods of producing human GLP-1 constitutively are provided as are method of producing GLP-1 and insulin or in a glucose-dependent manner using such transfected cells.

Abstract: Unique multifunctional nucleotide expression cassettes comprising a nucleotide sequence encoding a human protease driven by a glucose-regulatable promoter, a nucleotide sequence encoding human proinsulin having sites at its B-C and C-A junctions altered to permit cleavage by the human protease, and a CMV promoter driving the transcription of the nucleotide sequence encoding the human proinsulin, such cassettes optionally having polyadenylation sequences after each structural gene and the nucleotide sequence encoding human proinsulin optionally carrying an H10D variant, and cells transformed thereby.

Abstract: This invention relates to the therapeutic induction of supra-normal apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a promoter enhancer such that the inflammatory cells are targeted. In one embodiment, the chimeric gene comprises at least one TNF&agr; promoter enhancer attached to a functional copy of a minimal TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, wherein expression of the gene is driven by the TNF&agr; promoter. Examples of apoptosis-inducing genes include caspase-3, caspase-4, caspase-5, and Granzyme B. Advantageously, the TNFp-AIG chimeric gene is expressed in only those cells producing the inflammatory cytokine, TNF&agr;.

Abstract: This invention relates to chimeric nucleic acids and to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells the chimeric nucleic acid. The chimeric nucleic acid having at least one TNF&agr; promoter enhancer attached to a functional copy of a TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, which is further attached to a 3′UTR. The apoptosis-inducing gene is Granzyme B. The invention also relates to methods of making and using self-regulated apoptosis chimeric nucleic acids and pharmaceutical compositions containing them for treating inflammatory diseases.

Abstract: This invention relates to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a promoter enhancer such that the inflammatory cells are targeted. In one embodiment, the chimeric gene comprises at least one TNF&agr; promoter enhancer attached to a functional copy of a minimal TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, wherein expression of the gene is driven by the TNF&agr; promoter. Attachment can be direct, distal, proximal or combinations thereof. Example apoptosis-inducing genes include caspase 3, caspase 4, caspase 5, Granzyme B. Advantageously, the TNFp-AIG chimeric gene is expressed in only those cells producing the inflammatory cytokine, TNF&agr;.

Abstract: Unique multifunctional nucleotide expression cassettes comprising a nucleotide sequence encoding a human protease driven by a glucose-regulatable promoter, a nucleotide sequence encoding human proinsulin having sites at its B-C and C-A junctions altered to permit cleavage by the human protease, and a CMV promoter driving the transcription of the nucleotide sequence encoding the human proinsulin, such cassettes optionally having polyadenylation sequences after each structural gene and the nucleotide sequence encoding human proinsulin optionally carrying an H10D variant, and cells transformed thereby.

Abstract: Methods for maintaining and improving the secretory activity of cells housed in immunoisolation devices.