{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T06:52:36Z","timestamp":1761893556724},"reference-count":48,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[1998,6,1]],"date-time":"1998-06-01T00:00:00Z","timestamp":896659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[1998,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There are a number of reasons for choosing ornithine transcarbamylase (OTC) deficiency as a candidate for gene therapy: the gene has been cloned; the disorder is relatively common; the current clinical outcome is poor; and there are authentic animal models. In considering the development of gene therapy for OTC deficiency, we focused on the use of in vivo gene therapy with an adenoviral vector. Using the partially OTC\u2010deficient sparse fur mouse we found transduction and expression could be achieved using an intravenous infusion of a recombinant adenovirus containing the OTC cDNA. The results were transient as a result of immune activation in response to the vector and vector\u2010transduced cells. By modifying the adenoviral construct, creating an E1 deletion\u2013E2 temperature\u2010sensitive mutation, we blunted the cytotoxic T lymphocyte immune response and achieved correction of biochemical abnormalities for 2\u20133 months. We also found that transduction and expression following gene transfer occurred sufficiently rapidly to protect against acute hyperammonaemia within 24 h. Subsequent preclinical studies in mice and non\u2010human primates demonstrated that E1\u2013E4\u2010deleted vectors had a substantially improved safety profile and similar efficacy. With this evidence of efficacy and safety of adenoviral vectors, we are embarking on a phase I trial of intravascular gene transfer using an E1\u2013E4\u2010deleted vector in adults with partial OTC deficiency.<\/jats:p>","DOI":"10.1023\/a:1005369926784","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T21:48:34Z","timestamp":1040507314000},"page":"119-137","source":"Crossref","is-referenced-by-count":31,"title":["Developing adenoviral\u2010mediated in vivo gene therapy for ornithine transcarbamylase deficiency"],"prefix":"10.1002","volume":"21","author":[{"given":"S. E.","family":"Raper","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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