1. Hepatocyte-directed gene transfer in vivo leads to transient improvement of hypercholesterolemia in low density lipoprotein receptor-deficient rabbits
- Author
-
J R Chowdhury, G Y Wu, James M. Wilson, N R Chowdhury, Mariann Grossman, and C H Wu
- Subjects
medicine.medical_specialty ,Genetic enhancement ,Genetic transfer ,Cell Biology ,Familial hypercholesterolemia ,Biology ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Cell surface receptor ,In vivo ,Low-density lipoprotein ,Internal medicine ,LDL receptor ,medicine ,lipids (amino acids, peptides, and proteins) ,Receptor ,Molecular Biology - Abstract
Familial hypercholesterolemia is an inherited disease in humans, caused by a deficiency of low density lipoprotein (LDL) receptors, that we have used as a model for developing liver-directed gene therapies. Our strategy is to reconstitute hepatic LDL receptor expression in vivo by administering a DNA-protein complex that is capable of targeting the delivery of functional LDL receptor genes to hepatocytes. Infusion of this DNA-protein complex into the peripheral circulation of a rabbit animal model for familial hypercholesterolemia resulted in hepatocyte-specific gene transfer and a temporary amelioration of hypercholesterolemia. This noninvasive approach to gene therapy should have applications in the treatment of a wide spectrum of human diseases.
- Published
- 1992
- Full Text
- View/download PDF