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

American Association for the Advancement of Science (AAAS) - Tập 254 Số 5039 - Trang 1802-1805 - 1991
Jayanta Roy Chowdhury1, Mariann Grossman2, Sanjeev Gupta1, Namita Singh1, James R. Baker3, James M. Wilson2
1Department of Internal Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461.
2Howard Hughes Medical Institute, Departments of Internal Medicine and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109.
3Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.

Tóm tắt

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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American Association for the Advancement of Science (AAAS)

Tập 254 Số 5039

1802-1805

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