Title: Gene transfer by pyro-drive jet injector is a novel therapeutic approach for muscle diseases.
The angiogenic gene therapy is an attractive approach for the treatment of ischemic muscle diseases, including peripheral arterial disease and ischemic heart diseases. Although a variety of gene transfer methods have been developed, the efficiency of gene transfer is still limited. We have been developing the needleless high-energy bioinjector device, Pyro-drive Jet Injector (PJI), based on pyrotechnics using a combination of ignition powder and gunpowder, however, the utility of PJI in gene transfer into muscle tissues remains unclear. pcDNA3.1 plasmid containing Flag was injected to the thigh muscles of C57BL/6J mice using PJI or needle, as a control. Histological analysis demonstrated that the protein expression of Flag was observed in a wider range in PJI group than in needle group. To assess the validity of PJI for gene therapy, pcDNA3.1-human fibroblast growth factor 2 (FGF2), which has angiogenic activity and tissue protective properties, was injected into the ischemic thigh muscles with PJI or needle. ELISA assay revealed that the protein expression of FGF2 was increased in the thigh muscle tissues by PJI-mediated gene delivery. Significantly, histological analyses revealed that muscle fiber cross-sectional area and the number of endothelial marker CD31 (+) cells was increased in ischemic hind-limb tissues of the PJI-FGF2 group but not in those of needle-FGF2 group. To expand the applicability of the PJI-mediated gene transfer, pcDNA3.1-venus plasmid was injected into murine hearts with PJI or needle. PJI method was successful in gene transfer into murine hearts, especially into cardiomyocytes, with high efficiency when compared to needle method. Collectively, the non-needle, non-liposomal and non-viral gene transfer by PJI could be a novel therapeutic approach for muscle diseases.
['Nakae|Takafumi|T|', 'Obana|Masanori|M|', 'Maeda|Takahiro|T|', 'Ikeda|Akari|A|', 'Miyazaki|Hiroshi|H|', 'Tanaka|Shota|S|', 'Maeda|Makiko|M|', 'Yamashita|Kunihiko|K|', 'Terai|Kazuhiro|K|', 'Obika|Satoshi|S|', 'Fujio|Yasushi|Y|']
D000818:Animals D002460:Cell Line D016222:Fibroblast Growth Factor 2 D018014:Gene Transfer Techniques D015316:Genetic Therapy D005822:Genetic Vectors D006614:Hindlimb D006801:Humans D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018482:Muscle, Skeletal D009135:Muscular Diseases D009206:Myocardium D010957:Plasmids
Pyro-drive Jet Injector Gene delivery Cardiac muscles Skeletal muscles