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Does the use of recombinant AAV5 in pulmonary gene therapy lead to lung damage?
- Source :
- Respiratory Physiology & Neurobiology. 168:203-209
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
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) (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.
- Subjects :
- Male
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Time Factors
Physiology
Genetic enhancement
Genetic Vectors
Green Fluorescent Proteins
Apoptosis
Inflammation
Biology
Recombinant virus
Proinflammatory cytokine
Mice
Airway resistance
In Situ Nick-End Labeling
medicine
Animals
RNA, Messenger
Analysis of Variance
Mice, Inbred BALB C
Lung
Airway Resistance
General Neuroscience
Respiratory disease
Genetic Therapy
Pneumonia
respiratory system
medicine.disease
Disease Models, Animal
medicine.anatomical_structure
Respiratory Mechanics
medicine.symptom
Subjects
Details
- ISSN :
- 15699048
- Volume :
- 168
- Database :
- OpenAIRE
- Journal :
- Respiratory Physiology & Neurobiology
- Accession number :
- edsair.doi.dedup.....27ee56f8baae6d19b76718207e0d3a70