The use of a MITO-Porter to deliver exogenous therapeutic RNA to a mitochondrial disease’s cell with a A1555G mutation in the mitochondrial 12S rRNA gene results in an increase in mitochondrial respiratory activity

• Published in: Mitochondrion 2020-11, Vol.55, p.134-144
• Main Authors: Yamada, Yuma, Maruyama, Minako, Kita, Tomoko, Usami, Shin-ichi, Kitajiri, Shin-ichiro, Harashima, Hideyoshi
• Format: Article
• Language: English
• Subjects: A1555G mutation; Cell Line; Cell Respiration; Fibroblasts - cytology; Fibroblasts - metabolism; Humans; Liposomes; MITO-Porter; Mitochondria - physiology; Mitochondrial delivery; Mitochondrial Diseases - genetics; Mitochondrial Diseases - therapy; Mitochondrial gene therapy; Mitochondrial ribosomal RNA; Mutation; RNA, Ribosomal - genetics; RNA, Ribosomal - pharmacology; Transfection
• ISSN: 1567-7249; 1872-8278
• DOI: 10.1016/j.mito.2020.09.008

•We report on validating mitochondrial RNA therapeutic strategy by mitochondrial DDS.•Therapeutic rRNA was encapsulated in a mitochondrial targeting rRNA-MITO-Porter.•rRNA-MITO-Porter significantly improved mitochondrial activities of diseased cells. We report on validating a mitochondrial gene therapeutic strategy using fibroblasts derived from patients with an A1555G point mutation in mitochondrial DNA coding 12S ribosomal RNA (rRNA (12S)). Wild-type rRNA (12S) as a therapeutic RNA was encapsulated in a mitochondrial targeting liposome, a MITO-Porter (rRNA-MITO-Porter), and an attempt was made to deliver the MITO-Porter to mitochondria of the diseased cells. It was confirmed that the rRNA-MITO-Porter treatment significantly decreased the ratio of the mutant rRNA content. Moreover, it was shown that the mitochondrial respiratory activities of the diseased cells were improved as the result of the mitochondrial transfection of the rRNA-MITO-Porter.