Adeno-associated virus serotype 9 vectors transduce murine alveolar and nasal epithelia and can be readministered

Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):12993-8. doi: 10.1073/pnas.0601433103. Epub 2006 Aug 22.


Airway-directed gene transfer has emerged as a promising approach for the treatment of the two genetic diseases of the lung, namely cystic fibrosis and alpha-1-antitrypsin deficiency. Herein we describe the transduction efficiency of a novel adeno-associated virus (AAV) vector, AAV2/9, across murine nasal and lung airway epithelia. At the peak of gene expression AAV2/9-mediated human alpha-1-antitrypsin gene expression in serum was approximately 60-fold better than that of AAV2/5. We found that AAV2/9-mediated nLacZ gene transfer in nasal and lung airways was relatively stable for 9 months, suggesting that a progenitor airway cell population was transduced. Most interestingly, we show that AAV2/9 can be readministered in the presence of high levels of serum-circulating neutralizing antibodies as early as 1 month after initial exposure, with minimal effect on overall reporter gene expression, rendering it a promising gene transfer vector candidate for use in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Cell Differentiation
  • Chickens
  • Dependovirus / classification
  • Dependovirus / genetics*
  • Dependovirus / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Gene Expression
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacokinetics*
  • Genome, Viral / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Nasal Mucosa / cytology
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Alveoli / virology
  • Serotyping
  • Time Factors
  • Transduction, Genetic / methods*
  • Transgenes / genetics
  • alpha 1-Antitrypsin / genetics
  • beta-Galactosidase / metabolism


  • alpha 1-Antitrypsin
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • beta-Galactosidase