Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function?

Roberta M. Lassance, Caroline P. Pássaro, Sabrina V. Martini, Raquel C. Castiglione, Tatiana M. Gutierrez, Soraia C. Abreu, Mariana A. Antunes, Debora G. Xisto, Liudmila Cebotaru, Hilda Petrs-Silva, Walter A. Zin, William B. Guggino, Rafael Linden, Patricia R.M. Rocco, Marcelo M. Morales

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Forty-eight BALB/c mice were divided into two groups of 24 animals each. In the control group (CTRL) saline was intratracheally instilled, while the virus group (VR) received rAAV2-GFP (4 × 109 particles). These groups were subdivided into four sub-groups (n = 6). Pulmonary mechanical parameters were analyzed after 3 weeks (VR1d3w) and at 1 (VR2d1w), 2 (VR2d2w) and 3 weeks (VR2d3w) after a second AAV2 dose. Fractions of the area of alveolar collapse and the amount of polymorpho- and mononuclear cells were determined by point-counting technique. Viral transduction was evaluated by immunohistochemistry. Lung mechanical data were similar in all groups. However, there was an increase in airway and lung parenchyma cellularity and in the fraction of area of alveolar collapse in the VR2d2w group, which nonetheless decreased with time. There was no evidence of apoptosis in any group. In conclusion, the gene transfer vector AAV2 induces, in the lung, a discrete inflammatory reaction that does not affect either baseline lung mechanics or airway hyperresponsiveness.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalRespiratory Physiology and Neurobiology
Volume160
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Keywords

  • Adeno-associated virus type 2
  • Gene therapy
  • Pulmonary mechanics
  • Vector

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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  • Cite this

    Lassance, R. M., Pássaro, C. P., Martini, S. V., Castiglione, R. C., Gutierrez, T. M., Abreu, S. C., Antunes, M. A., Xisto, D. G., Cebotaru, L., Petrs-Silva, H., Zin, W. A., Guggino, W. B., Linden, R., Rocco, P. R. M., & Morales, M. M. (2008). Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function? Respiratory Physiology and Neurobiology, 160(1), 91-98. https://doi.org/10.1016/j.resp.2007.09.002