Gene therapy for phenylketonuria.

[classical phenylketonuria]

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 -deficient hepatocytes in vitro , but their present 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 .