Compositions and methods for treating endocrine, gastrointestinal or autoimmune disorders
Recombinant cells and methods are provided that relate to the use of isolated, engineered recombinant cells to directly or indirectly treat diseases or disorders in a mammalian host such as endocrine, gastrointestinal or autoimmune disorders. A recombinant cell is provided that comprises a signal sequence and a promoter, wherein: the signal sequence is capable of regulating signal-dependent expression of a target nucleic acid in a host or is capable of regulating signal-dependent expression of a target nucleic acid in response to an environmental stimulus, the cell is derived from an enteric or a commensal bacterium, and the target nucleic acid encodes a mammalian factor that promotes normal functioning of a physiological process in the host or is effective in preventing onset, establishment, or spread of a non-infectious disease in the host. The recombinant cell is administered to the host to treat the disease or disorder.
1. An isolated recombinant enteric, commensal bacterium that comprises a promoter linked to coding sequences that encodes a secretion tag and GLP-1(1-37),
wherein the recombinant enteric, commensal bacterium is a recombinant Lactobacillus bacterium wherein the promoter is an SlpA promoter having SEQ ID NO:20 and the secretion tag comprises USP45 secretion tags sequences and LEISS sequences.
2. An isolated recombinant enteric, commensal bacterium that comprises a promoter linked to coding sequences that encodes a secretion tag and GLP-1(1-37),
wherein the recombinant enteric, commensal bacterium is a recombinant Lactobacillus bacterium wherein the promoter is an SlpA promoter and the secretion tag comprises USP45 secretion tags sequences encoded by SEQ ID NO:21 and LEISS sequences encoded by SEQ ID NO:22.
3. An isolated recombinant enteric, commensal bacterium that comprises a promoter linked to coding sequences that encodes a secretion tag and GLP-1(1-37),
wherein the recombinant enteric, commensal bacterium is a recombinant Lactobacillus bacterium wherein the promoter is an SlpA promoter having SEQ ID NO:20, and USP45 secretion tags sequences encoded by SEQ ID NO:21, and LEISS sequences encoded by SEQ ID NO:22, and the coding sequence that encodes GLP-1(1-37) is SEQ ID NO:25.
4. An isolated recombinant enteric, commensal bacterium that comprises a promoter linked to coding sequences that encodes a secretion tag and GLP-1(1-37),
wherein the recombinant enteric, commensal bacterium is a recombinant E. coli bacterium comprising SEQ ID NO:4 or SEQ ID NO:10.