{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:25:25Z","timestamp":1760217925548,"version":"3.41.2"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T00:00:00Z","timestamp":1559001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adeno\u2010associated virus\u2010based vectors are efficient and safe drug candidates for different <jats:italic>in vivo<\/jats:italic> gene therapy applications. With increasing numbers of clinical studies based on AAV2 vectors that include not only rare, but also common diseases as a therapeutic target, there is an increased demand for the development of improved production technologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we compared two life cycle defective adenovirus mutants as helper viruses for AAV2 vector production. They had deletions either in the gene coding for the preterminal protein (pTP) that is expressed early in the viral life cycle and is essential for genome replication or in the gene coding for the 100K protein, a protein with many functions, one of which is involved in virus assembly. AAV2 vector production efficiencies were evaluated by analyzing genome\u2010containing particles using a real\u2010time polymerase chain reaction and functional units were investigated by transduction assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Somewhat contrary to our expectations, the \u2206100K mutant virus showed only a moderate efficiency as a helper virus for AAV2 vector production, whereas the replication\u2010deficient \u2206pTP mutant supported AAV2 production almost as efficiently as adenovirus wild\u2010type. We also showed that a temperature shift to 32\u00b0C together with extended incubation times improved AAV2 vector productivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study indicates the advantages of using a \u2206pTP mutant adenovirus rather than adenovirus wild\u2010type as a helper virus for AAV2 production and also indicates that temperature shifts to lower temperatures may improve AAV2 vector production rates.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3094","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T02:30:11Z","timestamp":1556677811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of life cycle defective adenovirus mutants for production of adeno\u2010associated virus 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