Does the use of recombinant AAV5 in pulmonary gene therapy lead to lung damage?
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) (4x10(11)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.
Martini
S V
SV
Laboratory of Cellular and Molecular Physiology, Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Ilha do Fundão, Rio de Janeiro, Brazil.
Fagundes
S S
SS
Schmidt
A C
AC
Avila
M
M
Ornellas
D S
DS
Ribas
V T
VT
Petrs-Silva
H
H
Linden
R
R
Faffe
D S
DS
Guggino
S E
SE
Rocco
P R M
PR
Zin
W A
WA
Morales
M M
MM
D000403:Airway Resistance; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000009:adverse effects*; D049452:Green Fluorescent Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D015656:Respiratory Mechanics / Q000502:physiology; D013997:Time Factors
D012333:RNA, Messenger; D049452:Green Fluorescent Proteins