Long-Term Improvement of Hypercholesterolemia After ex Vivo Gene Therapy in LDLR-Deficient Rabbits

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 transplant...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1991-12, Vol.254 (5039), p.1802-1805
Main Authors: Chowdhury, J. Roy, Grossman, Mariann, Gupta, Sanjeev, Chowdhury, N. Roy, Baker, James R., Wilson, James M.
Format: Article
Language:English
Subjects:
Albumins
Animals
beta-Galactosidase - analysis
beta-Galactosidase - genetics
Blood
Cell receptors
Cells
Cholesterol
Gene Expression
Gene therapy
Genetic Therapy
Genetics
Health aspects
Hepatocytes
Hypercholesterolemia
Hypercholesterolemia - genetics
Hypercholesterolemia - therapy
Liver
Liver - physiology
Liver Transplantation - physiology
Medical research
Rabbits
Receptors, LDL - analysis
Receptors, LDL - genetics
Recombinant Proteins - analysis
RNA
RNA - genetics
RNA - isolation & purification
Serum Albumin - analysis
Serum Albumin - genetics
Serum cholesterol
Spleen
Therapy
Transfection
Transplantation
Viruses
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1722351