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Condensation of Plasmid DNA Enhances Mitochondrial Association in Skeletal Muscle Following Hydrodynamic Limb Vein Injection

Laboratory for molecular design of pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan
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These authors contributed equally to this work.
Pharmaceuticals 2014, 7(8), 881-893; https://doi.org/10.3390/ph7080881
Received: 15 April 2014 / Revised: 15 July 2014 / Accepted: 15 August 2014 / Published: 21 August 2014
(This article belongs to the Special Issue Mitochondrial Target-Based Drug Discovery)
Mitochondrial gene therapy and diagnosis have the potential to provide substantial medical benefits. However, the utility of this approach has not yet been realized because the technology available for mitochondrial gene delivery continues to be a bottleneck. We previously reported on mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection. HLV injection, a useful method for nuclear transgene expression, involves the rapid injection of a large volume of naked plasmid DNA (pDNA). Moreover, the use of a condensed form of pDNA enhances the nuclear transgene expression by the HLV injection. The purpose of this study was to compare naked pDNA and condensed pDNA for mitochondrial association in skeletal muscle, when used in conjunction with HLV injection. PCR analysis showed that the use of condensed pDNA rather than naked pDNA resulted in a more effective mitochondrial association with pDNA, suggesting that the physicochemical state of pDNA plays a key role. Moreover, no mitochondrial toxicities in skeletal muscle following the HLV injection of condensed pDNA were confirmed, as evidenced by cytochrome c oxidase activity and mitochondrial membrane potential. These findings have the potential to contribute to the development for in vivo mitochondrial gene delivery system. View Full-Text
Keywords: mitochondrial gene delivery; hydrodynamic limb vein injection; condensed pDNA; mitochondrial gene therapy mitochondrial gene delivery; hydrodynamic limb vein injection; condensed pDNA; mitochondrial gene therapy
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Yasuzaki, Y.; Yamada, Y.; Fukuda, Y.; Harashima, H. Condensation of Plasmid DNA Enhances Mitochondrial Association in Skeletal Muscle Following Hydrodynamic Limb Vein Injection. Pharmaceuticals 2014, 7, 881-893.

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