title: Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice.
abstract: 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Eliana
authors.initials: E
authors.lastname: Barriocanal-Casado
authors.affiliation: Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.|Genomic Medicine Department. GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cueto-Ureña
authors.affiliation: Genomic Medicine Department. GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
authors.forename: Karim
authors.initials: K
authors.lastname: Benabdellah
authors.affiliation: Genomic Medicine Department. GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gutiérrez-Guerrero
authors.affiliation: Genomic Medicine Department. GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
authors.forename: Marién
authors.initials: M
authors.lastname: Cobo
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo-Gutiérrez
authors.affiliation: Genomic Medicine Department. GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Rodríguez-Sevilla
authors.affiliation: Genomic Medicine Department. GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martín
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Luis C
authors.identifier: http://orcid.org/0000-0003-3355-0298
authors.initials: LC
authors.lastname: López
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D010809:Physical Fitness; D014161:Transduction, Genetic; D014451:Ubiquinone / Q000096:biosynthesis
chemical_list: D024101:Mitochondrial Proteins; D014451:Ubiquinone