Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice Barriocanal Casado, Eliana Cueto-Ureña, Cristina Benabdellah, Karim Gutiérrez-Guerrero, Alejandra Cobo Pulido, Marién Hidalgo Gutiérrez, Agustín Rodriguez-Sevilla, Juan José Martín Molina, Francisco López García, Luis Carlos Mouse models Mitochondria Central nervous system Hyper expression techniques Fibroblasts RNA extraction Gene delivery Horses This study has been submitted to the patent's offices at the "University of Granada" and "Fundación Progreso y Salud". Please note that the results of this manuscript have been submitted to patent protection (application number P201630630; title: “Uses of Coenzyme Q biosynthetic proteins”; date:05/16/2016). Recent clinical trials have shown that in vivo and ex vivo gene therapy strategies can be an option for the treatment of several neurological disorders. Both strategies require efficient and safe vectors to 1) deliver the therapeutic gene directly into the CNS or 2) to genetically modify stem cells that will be used as Trojan horses for the systemic delivery of the therapeutic protein. A group of target diseases for these therapeutic strategies are mitochondrial encephalopathies due to mutations in nuclear DNA genes. In this study, we have developed a lentiviral vector (CCoq9WP) able to overexpress Coq9 mRNA and COQ9 protein in mouse embryonic fibroblasts (MEFs) and hematopoietic progenitor cells (HPCs) from Coq9R239X mice, an animal model of mitochondrial encephalopathy due to primary Coenzyme Q (CoQ) deficiency. Ectopic over-expression of Coq9 in both cell types restored the CoQ biosynthetic pathway and mitochondrial function, improving the fitness of the transduced cells. These results show the potential of the CCoq9WP lentiviral vector as a tool for gene therapy to treat mitochondrial encephalopathies. 2016-07-13T08:18:15Z 2016-07-13T08:18:15Z 2016 journal article Barriocanal-Casado, E.; et al. Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice. Plos One, 11(6): e0158344 (2016). [http://hdl.handle.net/10481/42131] 1932-6203 http://hdl.handle.net/10481/42131 10.1371/journal.pone.0158344 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Public Library of Science (PLOS)