Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts.
Adrenoleukodystrophy (ALD), a lethal demyelinating disease of the brain, is caused by mutations of a gene encoding an ATP-binding transporter, called ALDP, localized in the peroxisomal membrane. It is associated with a defective oxidation of very-long-chain fatty acids, leading to their accumulation in many tissues. This study reports that the retroviral-mediated transfer of the ALD cDNA restored very-long-chain fatty acid oxidation in ALD fibroblasts in vitro following abundant expression and appropriate targeting of the vector-encoded ALDP in peroxisomes. The same method may be used in hematopoietic cells as a further step of a gene therapy approach of ALD.
Cartier
N
N
Institut National de la Santé et de la Recherche Médicale U342, Université René Descartes, Hôpital Saint-Vincent de Paul, Paris, France.
Lopez
J
J
Moullier
P
P
Rocchiccioli
F
F
Rolland
M O
MO
Jorge
P
P
Mosser
J
J
Mandel
J L
JL
Bougnères
P F
PF
Danos
O
O
D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000628:therapy; D018076:DNA, Complementary / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000235:genetics; D012190:Retroviridae / Q000235:genetics
D018076:DNA, Complementary; D005227:Fatty Acids; D012333:RNA, Messenger