title: Effects of altering dosing on cationic liposome-mediated gene transfer to the respiratory epithelium.
abstract: Liposome-mediated gene transfer is currently sub-optimal with respect to both the extent and duration of transgene expression. We investigated whether simple changes in DNA dosing could enhance either of these outcomes. Increasing DNA doses produced highest transgene expression at an intermediate dose with toxicity observed at higher doses, thereby likely limiting expression. Adminis- tering an equivalent DNA dose in aliquots over a 1-3 day period resulted in significantly lower gene expression and did not increase the duration of expression. Administration at different times of the day (and hence wake/sleep cycles of the animals) did not alter gene expression. We conclude that such simple changes in dosing regimes are unlikely to contribute to improvements in gene transfer efficiency.
authors.affiliation: Department of Gene Therapy, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Hillery
authors.forename: S
authors.initials: S
authors.lastname: Cheng
authors.forename: D
authors.initials: D
authors.lastname: Geddes
authors.forename: E
authors.initials: E
authors.lastname: Alton
mesh_terms: D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003550:Cystic Fibrosis / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D051379:Mice; D013997:Time Factors; D019076:Transgenes
chemical_list: D008081:Liposomes; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase