Mitochondrial targeted meganuclease as a platform to eliminate mutant mtDNA in vivo

Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice.

Defects of mitochondrial DNA (mtDNA) maintenance have recently been associated with inherited neurodegenerative and muscle diseases and the aging process. Twinkle is a nuclear-encoded mtDNA helicase, dominant mutations of which cause adult-onset progressive external ophthalmoplegia (PEO) with multiple mtDNA deletions. We have generated transgenic mice expressing mouse Twinkle with PEO patient m...

Mitochondrial DNA (mtDNA)

Introduction: The Mitochondrion and Its Genome ............................................................ 1 The Human Mitochondrial Genome ................................................................................... 3 The D-loop and Human Population Genetics ..................................................................... 4 Mitochondrial DNA and Recent Human History .................

MitoTALEN: A General Approach to Reduce Mutant mtDNA Loads and Restore Oxidative Phosphorylation Function in Mitochondrial Diseases.

We have designed mitochondrially targeted transcription activator-like effector nucleases or mitoTALENs to cleave specific sequences in the mitochondrial DNA (mtDNA) with the goal of eliminating mtDNA carrying pathogenic point mutations. To test the generality of the approach, we designed mitoTALENs to target two relatively common pathogenic mtDNA point mutations associated with mitochondrial d...

Mmm1p, a Mitochondrial Outer Membrane Protein, Is Connected to Mitochondrial DNA (Mtdna) Nucleoids and Required for Mtdna Stability

In the yeast Saccharomyces cerevisiae, mitochondria form a branched, tubular reticulum in the periphery of the cell. Mmm1p is required to maintain normal mitochondrial shape and in mmm1 mutants mitochondria form large, spherical organelles. To further explore Mmm1p function, we examined the localization of a Mmm1p-green fluorescent protein (GFP) fusion in living cells. We found that Mmm1p-GFP i...

Nanogels as a Chemically Controllable Platform for Targeted Drug Delivery