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  • Title: Possibility of transkingdom gene therapy for complex I diseases.
    Author: Yagi T, Seo BB, Nakamaru-Ogiso E, Marella M, Barber-Singh J, Yamashita T, Matsuno-Yagi A.
    Journal: Biochim Biophys Acta; 2006; 1757(5-6):708-14. PubMed ID: 16581014.
    Abstract:
    Defects of complex I are involved in many human mitochondrial diseases, and therefore we have proposed to use the NDI1 gene encoding a single subunit NADH dehydrogenase of Saccharomyces cerevisiae for repair of respiratory activity. The yeast NDI1 gene was successfully introduced into mammalian cell lines. The expressed NDI1 protein was correctly targeted to the matrix side of the inner mitochondrial membranes, was fully functional and restored the NADH oxidase activity to the complex I-deficient cells. The NDI1-transduced cells were more resistant to complex I inhibitors and diminished production of reactive oxygen species induced by rotenone. It was further shown that the NDI1 protein can be functionally expressed in tissues such as skeletal muscles and the brain of rodents, which scarcely induced an inflammatory response. The use of NDI1 as a potential molecular therapy for complex I-deficient diseases is briefly discussed, including the proposed animal model.
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