Hepatocyte-directed gene transfer in vivo leads to transient improvement of hypercholesterolemia in low density lipoprotein receptor-deficient rabbits

James M. Wilson, Mariann Grossman, Catherine H. Wu, N. Roy Chowdhury, George Y. Wu, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

201 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)963-967
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number2
StatePublished - Jan 15 1992
Externally publishedYes

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Gene transfer
LDL Receptors
Hypercholesterolemia
Gene therapy
Hepatocytes
Hyperlipoproteinemia Type II
Rabbits
Genetic Therapy
Genes
Liver
DNA
Animals
Proteins
Animal Models
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hepatocyte-directed gene transfer in vivo leads to transient improvement of hypercholesterolemia in low density lipoprotein receptor-deficient rabbits. / Wilson, James M.; Grossman, Mariann; Wu, Catherine H.; Chowdhury, N. Roy; Wu, George Y.; Roy-Chowdhury, Jayanta.

In: Journal of Biological Chemistry, Vol. 267, No. 2, 15.01.1992, p. 963-967.

Research output: Contribution to journalArticle

Wilson, James M. ; Grossman, Mariann ; Wu, Catherine H. ; Chowdhury, N. Roy ; Wu, George Y. ; Roy-Chowdhury, Jayanta. / Hepatocyte-directed gene transfer in vivo leads to transient improvement of hypercholesterolemia in low density lipoprotein receptor-deficient rabbits. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 2. pp. 963-967.
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