Successful transgene expression with serial doses of aerosolized rAAV2 vectors in rhesus macaques

Anne C. Fischer, Suzanne E. Beck, Carolina I. Smith, Beth L. Laube, Frederic B. Askin, Sandra E. Guggino, Robert J. Adams, Terence B. Flotte, William B. Guggino

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Bronchoscopic microspraying of recombinant adeno-associated viral (rAAV) vectors targets high doses of vector directly to pulmonary epithelium. Single-dose endobronchial gene therapy trials have been accomplished in cystic fibrosis patients; however, repeated dosing strategies are likely essential for lifetime correction. These studies address whether serial reclosing with rAAV2 vectors results in an antiserotypic response and, furthermore, whether it triggers an inflammatory response prohibitive to transgene expression. Serial reclosing of 9 × 1011 infectious units of aerosolized rAAV2 vectors to rhesus macaques resulted in successful gene transfer by quantitative PCR (1.43 × 109 copies/g tissue) and transgene expression. Additionally, confocal microscopy and immunohistochemical analysis demonstrated in situ expression localized to the pulmonary epithelium. Although serial reclosing did induce a heightened anti-neutralizing antibody response in sera, gene transfer prevailed with resultant expression. This study is the first to demonstrate successful gene transfer subsequent to repeated aerosolized doses of rAAV2 in immunocompetent nonhuman primates without associated inflammatory responses prohibitive to transgene expression.

Original languageEnglish (US)
Pages (from-to)918-926
Number of pages9
JournalMolecular Therapy
Issue number6
StatePublished - Dec 2003


  • AAV
  • Aerosol
  • CFTR
  • Cystic fibrosis
  • GFP
  • Gene therapy
  • Microspraying

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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