Protein delivery by secretory gland expression
First Claim
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1. A method of reducing blood glucose levels in a diabetic mammalian subject, the method comprising:
- introducing into the pancreas of the mammalian subject a construct comprising an insulin-encoding DNA and a promoter sequence operably linked to the insulin-encoding DNA to facilitate expression in a eukaryotic cell, said introducing being by intraductal administration;
wherein expression of the introduced construct in the pancreas occurs such that a biologically active insulin polypeptide is delivered into the bloodstream of the patient in a therapeutically effective amount, and blood glucose levels in the mammalian subject are reduced.
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Abstract
Secretory gland cells, particularly pancreatic, hepatic, and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the bloodstream to obtain therapeutic levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term or short term therapies for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.
58 Citations
31 Claims
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1. A method of reducing blood glucose levels in a diabetic mammalian subject, the method comprising:
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introducing into the pancreas of the mammalian subject a construct comprising an insulin-encoding DNA and a promoter sequence operably linked to the insulin-encoding DNA to facilitate expression in a eukaryotic cell, said introducing being by intraductal administration; wherein expression of the introduced construct in the pancreas occurs such that a biologically active insulin polypeptide is delivered into the bloodstream of the patient in a therapeutically effective amount, and blood glucose levels in the mammalian subject are reduced. - View Dependent Claims (2, 3, 4, 5)
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6. A method of delivering a desired polypeptide to a mammalian subject, the method comprising:
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introducing in vivo into a lumen of a duct of a salivary gland and into a lumen of a duct of a liver of the mammalian subject a construct comprising a DNA of interest that encodes the desired polypeptide and a promoter sequence operably linked to the DNA of interest to facilitate expression in a eukaryotic cell; wherein the introduced construct is expressed in each of the salivary gland and the liver such that the polypeptide is delivered into the bloodstream of the mammal from each of the salivary gland and the liver. - View Dependent Claims (7, 8, 9, 10, 30, 31)
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11. A method of delivering a polypeptide to a mammalian subject, the method comprising:
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introducing in vivo into a lumen of a duct of a salivary gland and into a lumen of a duct of a pancreas of the mammalian subject a construct comprising a DNA of interest that encodes a desired polypeptide and a promoter sequence operably linked to the DNA of interest to facilitate expression in a eukaryotic cell; wherein the introduced construct is expressed in each of the salivary gland and the pancreas such that the polypeptide is delivered into the bloodstream of the mammalian subject from each of the salivary gland and the pancreas. - View Dependent Claims (12, 13, 14, 15, 16, 17)
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18. A method of delivering a polypeptide to a mammalian subject, the method comprising:
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administering directly in vivo into a lumen of a duct of a pancreas and into a lumen of a duct of a liver of the mammalian subject a construct comprising a DNA of interest that encodes a desired polypeptide and a promoter sequence operably linked to the DNA of interest to facilitate expression in a eukaryotic cell; wherein the introduced construct is expressed in each of the pancreas and the liver such that the polypeptide is delivered into the bloodstream of the mammal from each of the pancreas and the liver. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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Specification