Gene therapy for phenylketonuria using replication-defective recombinant adenovirus

Yutaka Nagasaki, Yoichi Matsubara, Kunihiro Fujii, Jun Akanuma, Hideaki Takano, Shigeo Kure, Kazutosi Takahashi, Kuniaki Narisawa, Yumi Kanegae, Izumu Saito

Research output: Contribution to journalArticlepeer-review

Abstract

Phenylketonuria (PKU) is due to deficiency of phenylalanine hydroxylase (PAH). It causes severe mental retardation, hypopigmentation and hyperphenylalanemia. Toward the gene therapy of PKU, we constructed a replication-defective recombinant adenovirus using a cosmid-cassette method. The adenovirus was administrated into tail veins of PKU model mice. Serum phenylalanine level decreased to less than 10% (2.2mg/dl) of the pre-treatment value (30.9mg/dl) within 24 hrs and lasted for 10 days. Daily subcutaneous injection of immunosuppresant FK506 after adenovirus injection prolonged the period to more than 35 days and allowed succesful repeated gene delivery. PAHcDNA was mainly detected in liver .PAH activity was present exclusively in liver. In these experiments, hypopigmented PKU mice showed pigmentation of hair, from grayish color to black. The study demonstrated the correction of physical phenotype as well as biochemical phenotype by gene transfer and efficacy of immunosuppresant for adenovirus-mediated gene therapy.

Original languageEnglish
Number of pages1
JournalJapanese Journal of Human Genetics
Volume42
Issue number1
Publication statusPublished - 1997 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)

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