The restriction endonuclease SmaI has been used for the diagnosis of neurogenic muscle weakness, ataxia and retinitis pigmentosa disease or Leigh’s disease, caused by the Mt8993T→G mutation which results in a Leu156Arg replacement that blocks proton translocation activity of subunit a of F₀F₁-ATPase. Our ultimate goal is to apply SmaI to gene therapy for this disease, because the mutant mitochondrial DNA (mtDNA) coexists with the wild-type mtDNA (heteroplasmy), and because only the mutant mtDNA, but not the wild-type mtDNA, is selectively restricted by the enzyme. For this purpose, we transiently expressed the SmaI gene fused to a mitochondrial targeting sequence in cybrids carrying the mutant mtDNA. Here, we demonstrate that mitochondria targeted by the SmaI enzyme showed specific elimination of the mutant mtDNA. This elimination was followed with repopulation by the wild-type mtDNA, resulting in restoration of both the normal intracellular ATP level and normal mitochondrial membrane potential. Furthermore, in vivo electroporation of the plasmids expressing mitochondrion-targeted EcoRI induced a decrease in cytochrome c oxidase activity in hamster skeletal muscles while causing no degenerative changes in nuclei. Delivery of restriction enzymes into mitochondria is a novel strategy for gene therapy of a special form of mitochondrial diseases.

Supersymmetric Ward identity for the low energy effective action in the standard background gauge is derived for arbitrary trajectories of supergravitons in Matrix Theory. In our formalism, the quantum-corrected supersymmetry transformation laws of the supergravitons are directly identified in closed form, which exhibit an intricate interplay between supersymmetry and gauge (BRST) symmetry. As an application, we explicitly compute the transformation laws for the source-probe configuration at 1-loop and confirm that supersymmetry fixes the form of the action completely, including the normalization, to the lowest order in the derivative expansion. † kazama@hep3.c.u-tokyo.ac.jp ‡ tetsu@hep1.c.u-tokyo.ac.jp S gg = Tr dτ 1 2 −∂ τ A + i B m , X m 2 −iTr dτ C∂ τ [D τ , C] − gC B m , [X m , C] . (2.18) 6

The restriction endonuclease Sinai has been used for the diagnosis of neurogenic muscle weakness, ataxia and retinitis pigmentosa disease or Leigh's disease, caused by the Mt8993T~G mutation which results in a Leu156Arg replacement that blocks proton translocation activity of subunit a of FoF1-ATPase. Our ultimate goal is to apply Sinai to gene therapy for this disease, because the mutant mitochondrial DNA (mtDNA) coexists with KARG E P~Fax+41 61 306 12 34 E-Mail karger@karger.ch w-~.~.karger, corn

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