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Intratumoral low-volume jet-injection for efficient nonviral gene transfer
Authors:Walther Wolfgang  Stein Ulrike  Fichtner Iduna  Voss Carsten  Schmidt Torsten  Schleef Martin  Nellessen Thomas  Schlag Peter M
Institution:Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. wowalt@mdc-berlin.de
Abstract:Jet-injection has become an applicable technology among other established nonviral delivery systems, such as particle bombardment or in vivo electroporation. The low-volume jet injector employed in this study uses compressed air to inject solutions of 1.5-10 microL containing naked DNA into the desired tissue. The novel design of this prototype makes multiple jet-injections possible. Therefore, repeated jet-injections into one target tissue can be performed easily. This jet-injector hand-held system was used for the direct in vivo gene transfer of plasmid DNA into tumors to achieve efficient expression of reporter genes (beta-galactosidase, green fluorescent protein GFP]) and of therapeutic genes (TNF-alpha) in different tumor models. The study presented here revealed the key parameters of efficient in vivo jet-injection (jet-injection volume, pressure, jet penetration, DNA stability) to define the optimal conditions for a jet-injection-aided nonviral gene therapy.
Keywords:Gene therapy  nonviral gene transfer  jet-injection  naked DNA  plasmid topology  plasmid stability
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