Does the use of recombinant AAV5 in pulmonary gene therapy lead to lung damage?

Abstract This study investigated whether repeated administration of recombinant adeno-associated virus type 5 (rAAV5) to the airways induces inflammatory processes in the lungs of BALB/c-mice, with mechanical and histologic changes. Saline was instilled intratracheally in the control group, and rAAV...

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Published in:Respiratory physiology & neurobiology 2009-09, Vol.168 (3), p.203-209
Main Authors: Martini, S.V, Fagundes, S.S, Schmidt, A.C, Avila, M, Ornellas, D.S, Ribas, V.T, Petrs-Silva, H, Linden, R, Faffe, D.S, Guggino, S.E, Rocco, P.R.M, Zin, W.A, Morales, M.M
Format: Article
Language:English
Subjects:
Adeno-associated virus 5
Adeno-associated virus type 5
Airway Resistance
Analysis of Variance
Animals
Apoptosis
Disease Models, Animal
Gene therapy
Genetic Therapy - adverse effects
Genetic Vectors - adverse effects
Green Fluorescent Proteins - genetics
In Situ Nick-End Labeling
Male
Medical Education
Mice
Mice, Inbred BALB C
Pneumonia - etiology
Pneumonia - pathology
Pulmonary mechanics
Pulmonary/Respiratory
Respiratory Mechanics - physiology
RNA, Messenger - metabolism
Time Factors
Vector
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Summary:Abstract This study investigated whether repeated administration of recombinant adeno-associated virus type 5 (rAAV5) to the airways induces inflammatory processes in the lungs of BALB/c-mice, with mechanical and histologic changes. Saline was instilled intratracheally in the control group, and rAAV5-green fluorescence protein (GFP) (4 × 1011 particles) in the virus group (VR). These groups were subdivided into four subgroups: one dose analyzed 3 weeks later (VR1d3w) and two doses analyzed 1 (VR2d1w), 2 (VR2d2w) and 3 weeks (VR2d3w) after the second dose. Lung morphometry, mechanical parameters, airway responsiveness, rAAV5-GFP transduction and the expression of inflammatory cytokines were investigated. No significant differences in lung mechanics, airway responsiveness, and morphometry were observed. Re-administration of rAAV5 vector resulted in a decrease in GFP mRNA expression in the VR2d3w group. There was no evidence of inflammatory response or apoptosis in any group. rAAV5 did not induce an inflammatory process, mechanical or morphometric changes in the lungs. AAV5 may be an appropriate vector for lung gene therapy.
ISSN:1569-9048
1878-1519
DOI:10.1016/j.resp.2009.06.016