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 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.
Chowdhury
J R
JR
Department of Internal Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Grossman
M
M
Gupta
S
S
Chowdhury
N R
NR
Baker
J R
JR
Wilson
J M
JM
D000818:Animals; D015870:Gene Expression; D015316:Genetic Therapy; D006937:Hypercholesterolemia / Q000235:genetics* / Q000628:therapy*; D008099:Liver / Q000502:physiology; D016031:Liver Transplantation / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011817:Rabbits; D011973:Receptors, LDL / Q000032:analysis / Q000235:genetics*; D011994:Recombinant Proteins / Q000032:analysis; D012709:Serum Albumin / Q000032:analysis / Q000235:genetics; D014162:Transfection; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D011973:Receptors, LDL; D011994:Recombinant Proteins; D012709:Serum Albumin; D012313:RNA; D001616:beta-Galactosidase