Expression of human phenylalanine hydroxylase activity in T lymphocytes of classical phenylketonuria children by retroviral-mediated gene transfer.

[classical phenylketonuria]

Classical phenylketonuria (PKU ) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH ) gene . At present , T lymphocyte-directed gene therapy is the only means for which a safety record has been established . Thus , we investigated the applicability of this strategy to PKU gene therapy . We first looked for tetrahydrobiopterin (BH 4 ) and dihydropteridine reductase (DHPR ) activity , which are required for the phenylalanine hydroxylation reaction and BH 4 regeneration , respectively , in T cells isolated from PKU children . We found that T cells contained a small amount of biopterin , but significant DHPR activity , and that the intracellular biopterin content could be increased by exogenous BH 4 supplementation . Moreover , PKU T cells were capable of taking up phenylalanine efficiently and effluxing acquired tyrosine . Finally , a recombinant retrovirus containing the human PAH cDNA was constructed and used to transduce isolated PKU T cells . Viral-transduced T cells produced high levels of PAH activity as compared to control mock-infected T cells . These results indicate that T lymphocytes express all that is required for synthesizing /replenishing constituents of the phenylalanine hydroxylation reaction and expressing transduced phenylalanine hydroxylase cDNA .

Diseases
Validation

Diseases presenting "high levels" symptom

22q11.2 deletion syndrome

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aromatase deficiency

cadasil

canavan disease

classical phenylketonuria

congenital adrenal hyperplasia

congenital toxoplasmosis

cutaneous mastocytosis

cystinuria

dentin dysplasia

dentinogenesis imperfecta

dracunculiasis

dystrophic epidermolysis bullosa

erythropoietic protoporphyria

gm1 gangliosidosis

hereditary cerebral hemorrhage with amyloidosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

kabuki syndrome

kallmann syndrome

liposarcoma

papillon-lefèvre syndrome

phenylketonuria

primary effusion lymphoma

primary hyperoxaluria type 1

scrub typhus

severe combined immunodeficiency

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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