title: Use of ultrasound to enhance nonviral lung gene transfer in vivo.
abstract: We have assessed if high-frequency ultrasound (US) can enhance nonviral gene transfer to the mouse lung. Cationic lipid GL67/pDNA, polyethylenimine (PEI)/pDNA and naked plasmid DNA (pDNA) were delivered via intranasal instillation, mixed with Optison microbubbles, and the animals were then exposed to 1 MHz US. Addition of Optison alone significantly reduced the transfection efficiency of all three gene transfer agents. US exposure did not increase GL67/pDNA or PEI/pDNA gene transfer compared to Optison-treated animals. However, it increased naked pDNA transfection efficiency by approximately 15-fold compared to Optison-treated animals, suggesting that despite ultrasound being attenuated by air in the lung, sufficient energy penetrates the tissue to increase gene transfer. US-induced lung haemorrhage, assessed histologically, increased with prolonged US exposure. The left lung was more affected than the right and this was mirrored by a lesser increase in naked pDNA gene transfer, in the left lung. The positive effect of US was dependent on Optison, as in its absence US did not increase naked pDNA transfection efficiency. We have thus established proof of principle that US can increase nonviral gene transfer, in the air-filled murine lung.
authors.affiliation: Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Xenariou
authors.forename: U
authors.initials: U
authors.lastname: Griesenbach
authors.forename: H-D
authors.initials: HD
authors.lastname: Liang
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: R
authors.initials: R
authors.lastname: Farley
authors.forename: L
authors.initials: L
authors.lastname: Somerton
authors.forename: C
authors.initials: C
authors.lastname: Singh
authors.forename: P K
authors.initials: PK
authors.lastname: Jeffery
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: R K
authors.initials: RK
authors.lastname: Scheule
authors.forename: S H
authors.initials: SH
authors.lastname: Cheng
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: M
authors.initials: M
authors.lastname: Blomley
authors.forename: E W F W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D000418:Albumins; D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D005466:Fluorocarbons; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011094:Polyethyleneimine; D014162:Transfection / Q000379:methods*; D014465:Ultrasonics
chemical_list: D000418:Albumins; C099458:FS 069; D005466:Fluorocarbons; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases