Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer

Gene Ther. 1994 Jul;1(4):247-54.


Classical phenylketonuria (PKU), which predisposes affected individuals to severe mental retardation, is caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). A recombinant adenoviral vector containing the human PAH cDNA was constructed and administered to PAH-deficient mice (strain PAHenu2). The hyperphenylalaninemic phenotype of these animals was completely normalized within 1 week of treatment. Although this therapeutic effect did not persist, analysis of the relationship between hepatic PAH activity and serum phenylalanine levels indicated that only 10-20% of normal enzymatic activity in the mouse liver is sufficient to restore normal serum phenylalanine levels. These results demonstrate that PKU and other metabolic disorders secondary to hepatic deficiencies can be completely corrected by gene therapy when more persistent vector systems are developed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Viral / blood
  • Base Sequence
  • Cell Line
  • DNA Primers / genetics
  • DNA, Recombinant / genetics
  • DNA, Recombinant / metabolism
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Liver / enzymology
  • Mice
  • Molecular Sequence Data
  • Phenotype
  • Phenylalanine Hydroxylase / deficiency
  • Phenylalanine Hydroxylase / genetics
  • Phenylketonurias / enzymology
  • Phenylketonurias / genetics
  • Phenylketonurias / therapy*
  • Tissue Distribution


  • Antibodies, Viral
  • DNA Primers
  • DNA, Recombinant
  • Phenylalanine Hydroxylase