Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo.
We have assessed whether magnetic forces (magnetofection) can enhance non-viral gene transfer to the airways. TransMAG(PEI), a superparamagnetic particle was coupled to Lipofectamine 2000 or cationic lipid 67 (GL67)/plasmid DNA (pDNA) liposome complexes. In vitro transfection with these formulations resulted in approximately 300- and 30-fold increase in reporter gene expression, respectively, after exposure to a magnetic field, but only at suboptimal pDNA concentrations. Because GL67 has been formulated for in vivo use, we next assessed TransMAG(PEI) in the murine nasal epithelium in vivo, and compared this to naked pDNA. At the concentrations required for in vivo experiments, precipitation of magnetic complexes was seen. After extensive optimization, addition of non-precipitated magnetic particles resulted in approximately seven- and 90-fold decrease in gene expression for naked pDNA and GL67/pDNA liposome complexes, respectively, compared to non-magnetic particles. Thus, whereas exposure to a magnetic field improved in vitro transfection efficiency, translation to the in vivo setting remains difficult.
Xenariou
S
S
Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College, 1B Manresa Road, London SW3 6LR, UK.
Griesenbach
U
U
Ferrari
S
S
Dean
P
P
Scheule
R K
RK
Cheng
S H
SH
Geddes
D M
DM
Plank
C
C
Alton
E W F W
EW
D000818:Animals; D002412:Cations; D045744:Cell Line, Tumor; D003550:Cystic Fibrosis / Q000378:metabolism / Q000628:therapy; D004247:DNA / Q000494:pharmacology*; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D008280:Magnetics; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D052638:Particulate Matter; D020545:Respiratory Mucosa / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D002412:Cations; D008055:Lipids; C086724:Lipofectamine; D052638:Particulate Matter; D004247:DNA