Fang B, Eisensmith R C, Li X H, Finegold M J, Shedlovsky A, Dove W, Woo S L
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
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.
典型苯丙酮尿症（PKU）会使患者易患严重智力发育迟缓，它是由肝脏苯丙氨酸羟化酶（PAH）缺乏引起的。构建了一种包含人PAH cDNA的重组腺病毒载体，并将其给予PAH缺陷小鼠（PAHenu2品系）。这些动物的高苯丙氨酸血症表型在治疗1周内完全恢复正常。尽管这种治疗效果没有持续，但对肝脏PAH活性与血清苯丙氨酸水平之间关系的分析表明，小鼠肝脏中仅10 - 20%的正常酶活性就足以恢复正常血清苯丙氨酸水平。这些结果表明，当开发出更持久的载体系统时，PKU和其他继发于肝脏缺陷的代谢紊乱可以通过基因治疗得到完全纠正。
