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Science 20 December 1991:
Vol. 254. no. 5039, pp. 1802 - 1805
DOI: 10.1126/science.1722351
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Articles
Science, Vol 254, Issue 5039, 1802-1805
Copyright © 1991 by American Association for the Advancement of Science
Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits
Chowdhury JR,
M Grossman,
S Gupta,
NR Chowdhury,
JR Baker Jr,
and
JM Wilson
Department of Internal Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Familial hypercholesterolemia (FH) is an inherited disorder in humans that is caused by a deficiency of low density lipoprotein receptors (LDLRs). An animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit, was used to develop an approach for liver-directed gene therapy based on transplantation of autologous hepatocytes that were genetically corrected ex vivo with recombinant retroviruses. Animals transplanted with LDLR-transduced autologous hepatocytes demonstrated a 30 to 50 percent decrease in total serum cholesterol that persisted for the duration of the experiment (122 days). Recombinant-derived LDLR RNA was harvested from tissues with no diminution for up to 6.5 months after transplantation.
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