{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:44:52Z","timestamp":1788425092011,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T00:00:00Z","timestamp":1300060800000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Classical phenylketonuria (PKU) arises from a deficiency of phenylalanine hydroxylase (PAH) that catalyses phenylalanine oxidation in the liver. Lack of PAH activity causes massive hyperphenylalaninemia and consequently severe brain damage. Preclinical studies showed that conventional adeno\u2010associated virus (AAV) vectors could correct hyperphenylalaninemia in a mouse model of PKU, although limitations such as very large dose requirement and relative inefficiency in female animals were recognized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>An AAV8\u2010pseudotyped vector was constructed with a self\u2010complementary AAV (scAAV) genome for efficient liver transduction and expression. Following vector injection to PKU mice, blood Phe was periodically measured by an enzymatic fluorometric assay. <jats:italic>In vivo<\/jats:italic> Phe oxidation was evaluated by a non\u2010invasive breath test using [1\u2010<jats:sup>13<\/jats:sup>C]Phe. Vector copy number in the host tissues was determined by quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A single injection of 1 \u00d7 10<jats:sup>11<\/jats:sup>\u20131 \u00d7 10<jats:sup>12<\/jats:sup> particles of the scAAV8 vector resulted in a reduction of blood Phe to normal or near\u2010normal levels for more than 1 year in both genders. The treated animals showed normal level of <jats:italic>in vivo<\/jats:italic> Phe oxidation. The presence of &gt; 1 copy of vector DNA per diploid genome in the liver was associated with normal blood Phe in the AAV\u2010treated PKU mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Complete phenotypic correction of PKU mice was achieved by the scAAV8 vector for the longest duration reported to date. The vector overcame the female\u2010specific disadvantage in AAV\u2010mediated liver transduction; thus, it offers a promising platform of long\u2010lasting gene therapy for PKU. 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