Intratumoral low-volume jet-injection for efficient nonviral gene transfer.
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.
Walther
Wolfgang
W
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. wowalt@mdc-berlin.de
Stein
Ulrike
U
Fichtner
Iduna
I
Voss
Carsten
C
Schmidt
Torsten
T
Schleef
Martin
M
Nellessen
Thomas
T
Schlag
Peter M
PM
D000818:Animals; D019075:Electrophoresis, Capillary; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D006801:Humans; D007277:Injections, Jet / Q000379:methods*; D007763:Lac Operon; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms; D010957:Plasmids / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D008164:Luminescent Proteins; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins