In vitro characterization and in vivo expression of human very-long chain acyl-CoA dehydrogenase

Molecular Genetics and Metabolism
J Lawrence MerrittDavid B Schowalter

Abstract

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of fatty acid beta-oxidation that can present at any age with cardiomyopathy, rhabdomyolysis, hepatic dysfunction, and/or nonketotic hypoglycemia. Through the expansion of newborn screening programs an increasing number of individuals with VLCAD deficiency are being identified prior to the onset of symptoms allowing early initiation of therapy. The development of a safe, durable, and effective VLCAD gene delivery system for use at the time of diagnosis could result in a significant improvement in the quality and duration of life for patients with VLCAD deficiency. To this end, we developed a construct containing the human VLCAD cDNA under the control of the strong CMV promoter (pCMV-hVLCAD). A novel rabbit polyclonal anti-VLCAD antibody was prepared using a 24 amino-acid peptide unique to the human VLCAD protein to study human VLCAD expression in immune competent mice. Antibody specificity was demonstrated in Western blots of human VLCAD deficient fibroblasts and in pCMV-hVLCAD transiently transfected VLCAD deficient fibroblasts. Transfected fibroblasts showed correction of the metabolic block as demonstrated by normalization of C14- and C16-acylcarnitine s...Continue Reading

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Citations

Jan 22, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·J Lawrence MerrittDavid B Schowalter
Jul 25, 2009·Nucleic Acids Research·Yao-Qing ShenGertraud Burger
Sep 5, 2008·Current Opinion in Neurology·Claudio Bruno, Salvatore Dimauro

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