U. Griesenbach et al., COMPARISON BETWEEN INTRATRACHEAL AND INTRAVENOUS ADMINISTRATION OF LIPOSOME-DNA COMPLEXES FOR CYSTIC-FIBROSIS LUNG GENE-THERAPY, Gene therapy, 5(2), 1998, pp. 181-188
Citations number
45
Categorie Soggetti
Biothechnology & Applied Migrobiology","Genetics & Heredity",Biology,"Medicine, Research & Experimental
Intratracheal (i.t.) and intravenous (i.v.) delivery of DNA-vector for
mulations are tow strategies to obtain gene transfer to the lung. It i
s still uncertain, however, which of these two modes of delivery will
be more effective in the treatment of cystic fibrosis and other lung d
iseases. In this study, we attempted to optimize formulations of the c
ationic liposome DODAC:DOPE mmonium-chloride:dioleoylphosphatidylethan
olamine) complexed to plasmids encoding chloramphenicol acetyltransfer
ase for i.t. and i.v. injection into CD-1 mice and compared the two me
thods. Our results showed that both methods conferred reporter gene ex
pression in the lung that was significantly higher relative to injecti
on of plasmid DNA alone. Expression using either mode of administratio
n was maximal 24 h after injection and declined to around 10% of day 1
levels 2 weeks after injection. For i.v. delivery of DODAC:DOPE-DNA c
omplexes multilamellar vesicles were more effective than large unilame
llar vesicles in all organs investigated. Recombinant DNA could be det
ected in the distal lung region following either route of administrati
on. However, i.t. administration predominantly led to DNA deposition i
n epithelial cells lining the brochioles, eg in clara cells, whereas i
.v. administration resulted in DNA deposition in the alveolar region o
f the lung including type II alveolar epithelial cells.