Efficient in vivo delivery of DNA to pulmonary cells using the novel lipid EDMPC.
We compared the efficacy of gene transfer in vitro and in vivo using various formulations of DNA-lipid complexes based on the novel cationic lipid EDMPC (1,2-dimyristoylsn-glycero-3-ethylphosphocholine, chloride salt). In vitro studies analyzed delivery of marker genes to four established cell lines, including two of pulmonary origin. The in vivo analysis used intralobar delivery of marker genes and CFTR to mice and rats. We observed a lack of positive correlation between those DNA-EDMPC formulations that delivered DNA most efficiently in vitro and those that worked best in vivo. Intralobar DNA delivery to rodents mediated by EDMPC was efficient. The high level of gene delivery by DNA-EDMPC formulations demonstrates that efficient lipid-mediated gene transfer to the lung is possible.
Gorman
C M
CM
Megabios Corporation, Burlingame, CA, USA.
Aikawa
M
M
Fox
B
B
Fox
E
E
Lapuz
C
C
Michaud
B
B
Nguyen
H
H
Roche
E
E
Sawa
T
T
Wiener-Kronish
J P
JP
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003550:Cystic Fibrosis / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA; D004134:Dimyristoylphosphatidylcholine / Q000031:analogs & derivatives; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D008081:Liposomes; D008168:Lung / Q000166:cytology*; D051379:Mice; D010714:Phosphatidylethanolamines; D051381:Rats; D017207:Rats, Sprague-Dawley
C108836:1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; D005819:Genetic Markers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D004134:Dimyristoylphosphatidylcholine