ABSTRACT
The application of gene therapy to liver disease is contingent on the development
of an effective gene delivery vehicle. Receptor-mediated endocytosis can be exploited
as a means of selective and efficient targeting of gene therapy vectors to hepatocytes.
DNA-binding conjugates have been directed to the liver by the attachment of asialoglycopro-teins
or other ligandsfor receptors expressed on hepatocytes. Recent studies suggest refinements
in this approach through which high transduction rates in vitro may be reproduced
in vivo. The intrinsic liver tropism of viral vectors and lipo-somes can be augmented
by the addition of targeting features, as demonstrated in animal models. With further
modification, such as the incorporation of hepatotropic elements of the hepatitis
viruses or lipoproteins, the next generation of delivery systems may achieve efficient,
persistent expression of therapeutic genes in a safe and cell type-specific manner.
KEY WORDS
gene therapy - receptor-mediated endocytosis - liposomes
