Vectors and methods of use
AssigneeChildren's Hospitals and Clinics of Minnesota
InventorJoseph LILLEGARD
Life of this patent
Estimating the term…
Abstract
This disclosure provides vectors and strategies for increasing the efficiency of gene therapy in hepatocytes. The efficiency of the delivery of a corrected gene or wild type gene is improved through the use of delivery to hepatocytes via intrahepatic (parenchyma) administration or administration via the portal vein. In addition, the corrected gene or wild type gene is delivered using an isolated exogenous nucleic acid comprising a promoter that is specifically expressed in hepatocytes. These methods and isolated exogenous nucleic acids are useful to correct gene defects in the liver such as inherited diseases of the liver.
Claims20
A lentiviral vector comprising an isolated exogenous nucleic acid coding for a functional phenylalanine hydroxylase protein or a functional fumarylacetoacetate hydrolase protein, the isolated exogenous nucleic acid under the control of an alpha1-antitrypsin (AAT) promoter and enhancer operably linked to the isolated exogenous nucleic acid.
A method of delivering an isolated exogenous nucleic acid coding for all or part of a polypeptide to a liver of a subject, the method comprising:
- administering the isolated exogenous nucleic acid to hepatocytes of the subject intrahepatically or via portal vein injection, the isolated exogenous nucleic acid comprising a nucleic acid coding for all of part of a polypeptide operably linked to a hepatocyte specific promoter and enhancer, wherein the polypeptide is a functional phenylalanine hydroxylase protein or a functional fumarylacetoacetate hydrolase protein.
A human hepatocyte comprising a lentiviral vector comprising an isolated exogenous nucleic acid coding for all or part of a polypeptide under the control of a hepatocyte specific promoter and enhancer linked to all or part of the isolated nucleic acid, the polypeptide comprising a functional fumarylacetoacetate hydrolase, a functional tyrosine transaminase, a functional 4-hydroxy-phenylpyruvate dioxygenase, or a functional phenylalanine hydroxylase.
Dependencies are inferred from the claim text.