RT Journal Article
T1 Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice.
A1 Barriocanal-Casado, Eliana
A1 Cueto-Ureña, Cristina
A1 Benabdellah, Karim
A1 Gutiérrez-Guerrero, Alejandra
A1 Cobo, Marién
A1 Hidalgo-Gutiérrez, Agustín
A1 Rodríguez-Sevilla, Juan José
A1 Martín, Francisco
A1 López, Luis C
AB 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.
YR 2016
FD 2016-06-24
LK http://hdl.handle.net/10668/10212
UL http://hdl.handle.net/10668/10212
LA en
DS RISalud
RD Apr 6, 2025