Abstract
Many "classic" mitochondrial diseases have been described that arise from single homoplasmic mutations in mitochondrial DNA (mtDNA). These diseases typically affect nonmitotic tissues (brain, retina, muscle), present with variable phenotypes, can appear sporadically, and are untreatable. Evolving evidence implicates mtDNA abnormalities in diseases such as Alzheimer's, Parkinson's, and type II diabetes, but specific causal mutations for these conditions remain to be defined. Understanding the mtDNA genotype-phenotype relationships and developing specific treatment for mtDNA-based diseases is hampered by inability to manipulate the mitochondrial genome. We present a novel protein transduction technology ("protofection") that allows insertion and expression of the human mitochondrial genome into mitochondria of living cells. With protofection, the mitochondrial genotype can be altered, or exogenous genes can be introduced to be expressed and either retained in mitochondria or be directed to other organelles. Protofection also delivers mtDNA in vivo, opening the way to rational development of mitochondrial gene replacement therapy of mtDNA-based diseases.
Citations
Dec 21, 2006·Pharmaceutical Research·Gerard G M D'SouzaVolkmar Weissig
Aug 30, 2011·Pharmaceutical Research·Lefkothea C Papadopoulou, Asterios S Tsiftsoglou
Aug 2, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Francesco Bruni, Robert N Lightowlers
Apr 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hong YuJohn Guy
Aug 1, 2007·Antioxidants & Redox Signaling·Russell H Swerdlow
Feb 23, 2011·Antioxidants & Redox Signaling·Russell H Swerdlow
Apr 21, 2009·Human Gene Therapy·Paula M KeeneyJames P Bennett
Mar 7, 2012·Human Gene Therapy·Shilpa IyerJames P Bennett
Sep 8, 2005·Rejuvenation Research·Rafal M Smigrodzki, Shaharyar M Khan
Sep 15, 2005·Nucleic Acids Research·Young Geol Yoon, Michael D Koob
Jun 8, 2011·Mechanisms of Ageing and Development·Daria MileshinaFrédérique Weber-Lotfi
Feb 2, 2010·Medical Hypotheses·M A Dani, S U Dani
Sep 1, 2006·Acta Neurologica Scandinavica·J Finsterer
Aug 5, 2011·Journal of Pineal Research·Tsung-I PengMei-Jie Jou
Jun 2, 2011·EMBO Reports·Robert N Lightowlers
Mar 11, 2005·Expert Opinion on Biological Therapy·Robert W Taylor
Jul 16, 2008·Biochimica Et Biophysica Acta·Roza KucharczykJean-Paul di Rago
Dec 24, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Charles C CaldwellRoberta Diaz Brinton
May 5, 2016·Ageing Research Reviews·Karen L DeBalsiWilliam C Copeland
Oct 7, 2015·Proceedings of the National Academy of Sciences of the United States of America·Hong YuJohn Guy
Jan 24, 2007·Journal of Neuroscience Research·Russell H Swerdlow
Jun 13, 2008·Biotechnology Journal
Dec 31, 2010·Anatomy & Cell Biology·Young Geol YoonYoung Hyun Yoo
Dec 4, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Anna Klucnika, Hansong Ma
May 4, 2017·Current Pathobiology Reports·Shilpa KulkarniChandan Guha
Sep 4, 2008·Human Gene Therapy·Stephen R Doyle, Chee Kai Chan
Sep 10, 2018·Biochemistry. Biokhimii︠a︡·N A VerechshaginaI O Mazunin
Jan 30, 2021·Cell Reports. Physical Science·Hongjian HeBing Xu