CpG-free plasmid DNA prevents deterioration of pulmonary function in mice.
Nonviral gene vectors have been shown to be therapeutically effective in various animal models of inherited and acquired lung diseases. Although an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response has been previously observed for first-generation plasmids, its effect on pulmonary function has not been investigated to date. Here, we present data on lung functional parameters together with histopathology, cellular and inflammatory events in response to pulmonary administration of DNA-containing particles. We show that aerosol delivery of polyethylenimine gene vectors containing a first-generation CpG-rich plasmid induced an inflammatory response which was associated with a decrease in lung compliance. In contrast to these observations, aerosol application of CpG-free plasmid DNA prevented immune response and impairment of pulmonary function. These results demonstrate that aerosol delivery of CpG-free plasmid DNA is critical to avoid alteration of pulmonary function. Therefore, we suggest to use CpG-free pDNA for gene delivery to the lungs in future.
Lesina
Eugenia
E
Department of Pediatrics, Ludwig Maximilian University, Munich, Germany.
Dames
Petra
P
Flemmer
Andreas
A
Hajek
Kerstin
K
Kirchner
Thomas
T
Bittmann
Iris
I
Rudolph
Carsten
C
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018899:CpG Islands / Q000235:genetics*; D016207:Cytokines / Q000276:immunology; D004247:DNA / Q000008:administration & dosage*; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D004339:Drug Compounding; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D049409:Luciferases, Firefly / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000628:therapy; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000009:adverse effects / Q000737:chemistry*; D012129:Respiratory Function Tests; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*
D000336:Aerosols; D016207:Cytokines; D004337:Drug Carriers; D011094:Polyethyleneimine; D004247:DNA; D049409:Luciferases, Firefly