A genetic therapy for familial hypercholesterolemia.
The WHHL rabbit serves as an animal model for the human genetic disease, familial hypercholesterolemia. In initial studies aimed at the development of a genetic therapy for familial hypercholesterolemia (i.e., introduction of a normal LDL receptor gene), WHHL rabbit skin fibroblasts were transduced with a retroviral vector expressing a normal human LDL receptor. Correction of the WHHL rabbit genetic defect in vitro was confirmed. Autologous fibroblasts expressing LDL receptors were reimplanted in donor rabbits and were found to survive and express the recombinant receptor in vivo for up to 4 weeks. In vivo LDL receptor expression by autologous cells stably transduced with functioning LDL receptors is possible. Transduction of greater numbers of cells along with increased cell survival in vivo may eventually lead to a specific and effective genetic therapy for familial hypercholesterolemia.
Dichek
D A
DA
Molecular Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Bratthauer
G L
GL
Beg
Z H
ZH
Newman
K D
KD
Anderson
K D
KD
Zwiebel
J A
JA
Hoeg
J M
JM
Anderson
W F
WF
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014162:Transfection
D011973:Receptors, LDL