title: [MITO-Porter; a cutting-edge technology for mitochondrial gene therapy].
abstract: Gene therapy is an attractive strategy, for not only targeting nuclear genome, but the mitochondrial genome as well. Human mitochondrial DNA (mtDNA) encodes 13 subunits of the electron transport chain, 22 tRNAs, and 2 rRNAs and their mutations cause a wide range of mitochondrial diseases. Each cell contains hundreds to thousands of mtDNAs, and in the case of a diseased cell, the mitochondrion possesses both mutant mtDNA and wild-type mtDNA. It is generally accepted that the disease phenotype appears when the proportion of the pathogenic mutant mtDNA exceeds a certain threshold. Therefore, the suppression of mutant mtDNA or supplementing wild-type mtDNA will control the onset of mitochondrial disease. To achieve the transfection of an exogenous therapeutic gene to the mitochondrial matrix where mtDNA is transcribed and translated, it is necessary to transfer cargos through mitochondrial outer and inner membranes. Several methods have been examined for mitochondrial transfection, but a universal, wide-ranging transfection technique has yet not been established. We recently developed a mitochondrial targeting delivery system, namely the MITO-Porter. The MITO-Porter is liposomal nanocarrier with a mitochondrial fusogenic lipid composition. We reported that the MITO-Porter could deliver chemical compounds and proteins to the mitochondrial matrix via membrane fusion. In this review, we report (1) on the pharmacological enhancement of lecithinized superoxide dismutase (PC-SOD) using MITO-Porter, (2) the transcription activation of exogenous DNA by mitochondrial transcription factor A (TFAM), and (3) perspectives on a mitochondrial targeting device.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. furukawa-ryo@mail.sci.hokudai.ac.jp
authors.forename: Ryo
authors.initials: R
authors.lastname: Furukawa
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D004272:DNA, Mitochondrial / Q000008:administration & dosage* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008561:Membrane Fusion; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000628:therapy*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000502:physiology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D049329:Nanostructures; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection / Q000379:methods
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D008081:Liposomes; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D004247:DNA; D013482:Superoxide Dismutase