title: Mitochondrial gene therapy: an arena for the biomedical use of inteins.
abstract: Mitochondrial DNA (mtDNA) mutations underlie many rare diseases and might also contribute to human ageing. Gene therapy is a tempting future possibility for intervening in mitochondriopathies. Expression of the 13 mtDNA-encoded proteins from nuclear transgenes (allotopic expression) might be the most effective gene-therapy strategy. Its only confirmed difficulty is the extreme hydrophobicity of these proteins, which prevents their import into mitochondria from the cytosol. Inteins (self-splicing 'protein introns') might offer a solution to this problem: their insertion into such transgenes could greatly reduce the encoded proteins' hydrophobicity, enabling import, with post-import excision restoring the natural amino acid sequence.
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, UK CB2 3EH. ag24@gen.cam.ac.uk
authors.forename: A D
authors.initials: AD
authors.lastname: de Grey
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends*; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D019154:Protein Splicing / Q000235:genetics*