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Publication Number
US-9339519-B2
Publication Date
2016-05-17
Expiration Date
Abstract
The present invention provides certain animals, and in particular porcine animals, tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (αGT) and express one or more additional transgenes which make them suitable donors for pancreatic islet xenotransplantation. Methods of treatment and prevention of diabetes using cells derived from such animals are also provided.
Core Innovation
The invention relates to a genetically modified transgenic porcine animal in which genetic modifications result in the lack of any expression of functional alpha 1,3-galactosyltransferase (GTKO). The porcine genome also incorporates a human CD46 transgene under the control of the human CD46 promoter, with expression in at least pancreatic islet cells and tissues.
In addition to GTKO and human CD46, the porcine animal incorporates and expresses at least one immunosuppressant transgene and at least one anticoagulant transgene under the control of an islet-specific promoter in pancreatic islet cells and tissues. The phenotype is characterized by specific expression of the anticoagulant and immunosuppressant transgenes in pancreatic islet cells and tissues.
Transgenic porcine islet cells isolated from the porcine animal produce insulin and, after transplantation into a host, reduce the instant blood mediated inflammatory reaction (IBMIR) in comparison to non-transgenic porcine islet cells. The disclosed scope emphasizes pancreatic islet xenotransplantation for diabetes treatment or prevention.
Claims Coverage
The independent claim defines four inventive features: GTKO, human CD46 under the human CD46 promoter, islet-specific immunosuppressant transgene expression, and islet-specific anticoagulant transgene expression, together with insulin production and reduced IBMIR after transplantation.
Genetically modified transgenic porcine animal with GTKO and human CD46 under the human CD46 promoter
The genome results in lack of any expression of functional alpha 1,3-galactosyltransferase and incorporates a human CD46 transgene under control of the human CD46 promoter, with expression in at least pancreatic islet cells and tissues.
Islet-specific immunosuppressant transgene expression
The genome incorporates and expresses at least one immunosuppressant transgene under control of an islet-specific promoter in pancreatic islet cells and tissues.
Islet-specific anticoagulant transgene expression
The genome incorporates and expresses at least one anticoagulant transgene under control of an islet-specific promoter in pancreatic islet cells and tissues.
Insulin-producing islet cells that reduce IBMIR after transplantation
Transgenic porcine islet cells isolated from the porcine animal produce insulin and reduce the instant blood mediated inflammatory reaction (IBMIR), in comparison to non-transgenic porcine islet cells, after transplantation into a host.
The claim integrates GTKO and human CD46 expressed via the human CD46 promoter in pancreatic islet cells with islet-specific expression of immunosuppressant and anticoagulant transgenes, and requires insulin production and reduced IBMIR after transplantation versus non-transgenic porcine islet cells.
Stated Advantages
Reduces the instant blood mediated inflammatory reaction (IBMIR) after transplantation compared to non-transgenic porcine islet cells.
Transgenic porcine islet cells produce insulin after transplantation into a host.
Documented Applications
Transplantation of transgenic porcine islet cells into a host.
Pancreatic islet xenotransplantation for diabetes treatment or prevention.
Type 1 diabetes treatment/prevention.
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