{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:58:03Z","timestamp":1790499483602,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cystic fibrosis is an autosomal-recessive disease that is caused by a mutant CFTR (cystic fibrosis transmembrane conductance regulator) gene and is characterized by chronic bacterial lung infections and inflammation. Complementation with functional CFTR normalizes anion transport across the airway surface. Adeno-associated virus (AAV) is a useful vector for gene therapy because of its low immunogenicity and ability to persist for months to years. However, because its episomal expression may decrease after cell division, readministration of the AAV vector may be required. To overcome this, we designed an integrating AAV-based CFTR-expressing vector, termed piggyBac (PB)\/AAV, carrying CFTR flanked by the terminal repeats of the piggyBac transposon. With codelivery of the piggyBac transposase, PB\/AAV can integrate into the host genome. Because of the packaging constraints of AAV, careful consideration was required to ensure that the vector would package and express its CFTR cDNA cargo. In this short-term study, PB\/AAV-CFTR was aerosolized to the airways of CF pigs in the absence of the transposase. Two weeks later, transepithelial Cl\u2212 current was restored in freshly excised tracheal and bronchial tissue. Additionally, we observed an increase in tracheal airway surface liquid pH and bacterial killing in comparison with untreated CF pigs. Airway surface liquid from primary airway cells cultured from treated CF pigs exhibited increased pH correlating with decreased viscosity. Together, these results show that complementing CFTR in CF pigs with PB\/AAV rescues the anion transport defect in a large-animal CF model. Delivery of this integrating viral vector system to airway progenitor cells could lead to persistent, life-long expression in vivo.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0006oc","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T11:01:06Z","timestamp":1560250866000},"page":"747-754","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":42,"title":["A Novel AAV-mediated Gene Delivery System Corrects CFTR Function in Pigs"],"prefix":"10.1093","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-9138","authenticated-orcid":false,"given":"Ashley L.","family":"Cooney","sequence":"first","affiliation":[{"name":"Stead Family Department of Pediatrics"},{"name":"Pappajohn Biomedical Institute"},{"name":"Center for Gene Therapy, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Thornell","sequence":"additional","affiliation":[{"name":"Pappajohn 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Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Paul B.","family":"McCray","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics"},{"name":"Pappajohn Biomedical Institute"},{"name":"Center for Gene Therapy, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zabner","sequence":"additional","affiliation":[{"name":"Pappajohn Biomedical Institute"},{"name":"Center for Gene Therapy, and"},{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L.","family":"Sinn","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics"},{"name":"Pappajohn Biomedical Institute"},{"name":"Center for Gene Therapy, 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