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Despite progresses made in identification of their molecular bases, nearly everything remains to be done as regards therapy. Research dealing with mitochondrial physiology and pathology has &gt;20 years of history around the world. We are involved, as are many other laboratories, in the challenge of finding ways to fight these diseases. However, our main limitation is the scarcety of animal models required for both understanding the molecular mechanisms underlying the diseases and evaluating therapeutic strategies. This is especially true for diseases due to mutations in mitochondrial DNA (mtDNA), since an authentic genetic model of mtDNA mutations is technically a very difficult task due to both the inability of manipulating the mitochondrial genome of living mammalian cells and to its multicopy nature. This has led researchers in the field to consider the prospect of gene therapy approaches that can roughly be divided into three groups: (1) import of wild\u2010type copies or relevant sections of DNA or RNA into mitochondria, (2) manipulation of mitochondrial genetic content, and (3) rescue of a defect by expression of an engineered gene product from the nucleus (allotopic or xenotropic expression). We briefly introduce these concepts and indicate where promising progress has been made in the last decade.<\/jats:p>","DOI":"10.1007\/s10545-010-9131-5","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T14:35:28Z","timestamp":1277217328000},"page":"327-344","source":"Crossref","is-referenced-by-count":27,"title":["Mitochondrial medicine: to a new era of gene therapy for mitochondrial DNA mutations"],"prefix":"10.1002","volume":"34","author":[{"given":"H\u00e9l\u00e8ne","family":"Cwerman\u2010Thibault","sequence":"first","affiliation":[{"name":"INSERM, U968 Paris 75012 France"},{"name":"UPMC Univ Paris 06, UMR_S 968 Institut de la Vision Paris 75012 France"},{"name":"CNRS, UMR_7210 Paris 75012 France"},{"name":"Centre Hospitalier National d'Ophtalmologie des Quinze\u2010Vingts INSERM\u2010DHOS CIC 503 Paris 75012 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