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Gene therapy for phenylketonuria
Author(s) -
Eisensmith RC,
Woo SLC
Publication year - 1994
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.1994.tb13471.x
Subject(s) - phenylalanine hydroxylase , genetic enhancement , recombinant dna , medicine , somatic cell , phenylalanine , vector (molecular biology) , complementary dna , viral vector , gene , in vivo , retrovirus , transduction (biophysics) , in vitro , endocrinology , genetics , biology , biochemistry , amino acid
Classical phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). Three different vector systems have been developed to examine the potential of somatic gene therapy for the treatment of PKU. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH‐deiicient hepatocytes in vitro, but their present phenylketonuria, retrovirus application is limited by their low transduction efficiency in vivo. In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH‐deficient mice restores 10‐80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. At present, this effect is transient and re‐administration has no further effect. However, this result suggests that PKU can be completely corrected by somatic gene therapy as more persistent vectors are developed.