Intratumoral low-volume jet-injection for efficient nonviral gene transfer |
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Authors: | Walther Wolfgang Stein Ulrike Fichtner Iduna Voss Carsten Schmidt Torsten Schleef Martin Nellessen Thomas Schlag Peter M |
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Affiliation: | Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. wowalt@mdc-berlin.de |
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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. |
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Keywords: | Gene therapy nonviral gene transfer jet-injection naked DNA plasmid topology plasmid stability |
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