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Protective effect of recombinant adeno-associated virus 2/8-mediated gene therapy from the maternal hyperphenylalaninemia in offsprings of a mouse model of phenylketonuria

Title
Protective effect of recombinant adeno-associated virus 2/8-mediated gene therapy from the maternal hyperphenylalaninemia in offsprings of a mouse model of phenylketonuria
Authors
Jung S.-C.Park J.-W.Oh H.-J.Choi J.-O.Seo K.-I.Park E.-S.Park H.-Y.
Ewha Authors
박혜영정성철박주원
SCOPUS Author ID
박혜영scopus; 정성철scopus; 박주원scopus
Issue Date
2008
Journal Title
Journal of Korean Medical Science
ISSN
1011-8934JCR Link
Citation
vol. 23, no. 5, pp. 877 - 883
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
Abstract
Phenylketonuria (PKU) is an autosomal recessively inherited metabolic disorder caused by a deficiency of phenylalanine hydroxylase (PAH). The accumulation of phenylalanine leads to severe mental and psychomotor retardation, and the fetus of an uncontrolled pregnant female patient presents with maternal PKU syndrome. We have reported previously on the cognitive outcome of biochemical and phenotypic reversal of PKU in a mouse model, Pahenu2, by the AAV serotype 2-mediated gene delivery of a human PAH transgene. However, the therapeutic efficacy had been limited to only male PKU mice. In this study, we generated a pseudotyped recombinant AAV2/8-hPAH vector and infused it into female PKU mice through the hepatic portal vein or tail vein. Two weeks after injection, complete fur color change to black was observed in female PKU, as in males. The PAH activity in the liver increased to 65-70% of the wild-type activity in female PKU mice and to 90% in male PKU mice. Plasma phenylalanine concentration in female PKU mice decreased to the normal value. In addition, the offsprings of the treated female PKU mice can rescue from the harmful effect of maternal hyperphenylalaninemia. These results indicate that recombinant AAV2/8-mediated gene therapy is a potential therapeutic strategy for PKU. Copyright ©The Korean Academy of Medical Sciences.
DOI
10.3346/jkms.2008.23.5.877
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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