Magnet-guided transduction of mammalian cells and mice using engineered magnetic lentiviral particles.
Targeted delivery of therapeutic transgenes into specific cells remains a highly relevant challenge for tissue engineering and future gene-based therapies. We have designed streptavidin-pseudotyped lentiviral particles which upon coupling with biotinylated magnetic carbon-coated cobalt nanoparticles could be guided by magnetic fields to site-specifically transduce desired target cells in culture as well as in mice. Magnetic patterns projected onto monolayer cultures were replicated by fluorescent cells following targeted transduction by magnetic lentiviral particles engineered for constitutive expression of the green fluorescent protein (GFP). Even after intravenous injection into mice magnetic GFP-transgenic lentiviral particles could be guided to a preferred transduction site in the animal using a magnetic field. Magnet-guided transgene delivery producing desired patterns of transduced cell populations may enable the design of defined tissue topologies and provide site-specific transduction of therapeutic transgenes for cell-specific interventions in future gene and cancer therapies.
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Wilfried
W
Weber
Cédric
C
Lienhart
Marie
M
Daoud-El Baba
Robert N
RN
Grass
Thomas
T
Kohler
Ralph
R
Müller
Wendelin J
WJ
Stark
Martin
M
Fussenegger
D000818:Animals; D001710:Biotin / Q000378:metabolism; D002460:Cell Line; D004574:Electromagnetic Fields; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D019809:Streptavidin / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes
D049452:Green Fluorescent Proteins; D001710:Biotin; D019809:Streptavidin