Abstract
Mitochondria resulted from an endosymbiosis event and subsequently kept their own genome. In the course of evolution, the mitochondrial DNA shrunk down but it still encodes essential components of the oxidative phosphorylation chain. Point mutations and deletions in the human mitochondrial DNA cause severe incurable neurodegenerative diseases and accumulate during aging. Rearrangements in the plant mitochondrial genome contribute to evolution and agronomical traits. Development of human mitochondrial gene therapy strategies or plant mitochondrial biotechnologies suffer from the inability of conventional methodologies to genetically transform mitochondria. The importance of these issues led to the development of a large set of alternative strategies aiming to target DNA or RNA into mitochondria, mainly in mammalian cells. A first group relied on natural RNA uptake pathways of mitochondria, using tRNA derivatives, tRNA mimics, 5S rRNA, and stem-loop structures of RNase P and RNase MRP RNAs as import shuttles, or taking a special RNA import complex as a carrier. Other strategies took advantage of the regular protein uptake pathway of mitochondria to design a series of DNA or RNA-binding plaforms driven to the organelles by mitochondrial targeting peptides. In a third category of approaches, elaborate DNA-binding lipophilic vesicles were rendered mitochondriotropic and served as carriers for organelle targeting. Finally, atypical protocols like hydrodynamic vein injection and magnetofection were adapted for the challenge. A number of these methodologies were claimed to be successful on the basis of functional or genetic observations, but there is still little consensus in the field.
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Acknowledgments
We acknowledge support of our work by the French Centre National de la Recherche Scientifique (CNRS, UPR2357), the University of Strasbourg, the Agence Nationale de la Recherche (grant numbers ANR-06-MRAR-037-02, ANR-09-BLAN-0240-01) and the Ministère de la Recherche et de l’Enseignement Supérieur (Investissements d’Avenir/Laboratoire d’Excellence MitoCross, grant number ANR-11-LABX-0057_MITOCROSS).
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Weber-Lotfi, F., Dietrich, A. (2018). Targeting Therapeutic Nucleic Acids into Mitochondria: A Long Challenge. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_25
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