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Progress and prospects: Gene therapy for mitochondrial DNA disease

Lookup NU author(s): Dr Pierre Boesch, Professor Robert Taylor, Professor Robert Lightowlers



Defects of the mitochondrial genome cause a wide variety of clinical disorders. Except for rare cases where surgery or transplant is indicated, there is no effective treatment for patients. Genetic-based therapies are consequently being considered. On account of the difficulties associated with mitochondrial (mt) transfection, alternative approaches whereby mitochondrial genes can be engineered and introduced into the nucleus (allotopic expression) are being attempted with some success, at least in cultured cells. Defects in the activities of multi-subunit complexes of the oxidative phosphorylation apparatus have been circumvented by the targeted expression of simple single subunit enzymes from other species (xenotopic expression). Although far from the clinic, these approaches show promise. Similarly, nuclear transfection with genes encoding restriction endonucleases or sequence-specific zinc finger-binding proteins destined for mitochondria has also proved successful in targeting mtDNA-borne pathogenic mutations. This is particularly important, as mutated mtDNA is often found in cells that also contain normal copies of the genome, a situation termed heteroplasmy. Shifting the levels of heteroplasmy towards the normal mtDNA has become the goal of a variety of invasive and non-invasive methods, which are also highlighted in this review.

Publication metadata

Author(s): Kyriakouli D, Boesch P, Taylor R, Lightowlers R

Publication type: Review

Publication status: Published

Journal: Gene Therapy

Year: 2008

Volume: 15

Issue: 14

Pages: 1017-1023

Print publication date: 01/07/2008

ISSN (print): 0969-7128

ISSN (electronic): 1476-5462


DOI: 10.1038/gt.2008.91