Mitochondria are the power plants of the cell, and slowly accumulating damage to the DNA that they contain, distinct from the DNA in the cell nucleus, is thought to be an important contribution to degenerative aging. Further, a range of inherited conditions are caused by genetic errors in mitochondrial DNA, such as Leber's hereditary optic neuropathy.
The SENS Research Foundation is working on ways to eliminate the effects of accumulated mitochondrial DNA (mtDNA) damage in order to build a therapy for aging, and other groups are working on methods of mitochondrial repair aimed at treating inherited mitochondrial disease. Below you'll find recent news of progress from one of those groups. The researchers have a method that should be applicable as a means to reverse the mitochondrial DNA damage that contributes to aging. That damage is centered on thirteen important genes, so can in principle targeted by any one-gene-at-a-time method like the one demonstrated here:
Searching for strategies to repair mitochondrial gene defects, a group of [investigators] explored proteins called transcription activator-like (TAL) effectors. In nature, TAL effectors are found only in certain types of plant-infecting bacteria. They enable the bacteria to use plant DNA to multiply and spread infection.
Scientists recently began using TAL effectors to modify DNA in a variety of organisms. In the lab, TAL effectors can be fused with DNA-breaking proteins called nucleases. These TAL effector nucleases (TALENs) can be used to add or remove specific genes or correct gene mutations - techniques that fall under the broad category of genome editing. During the past few years, scientists have begun adapting TALENs and other genome-editing tools for gene therapy. Until now, scientists had only used TALENs to edit genes in the cell nucleus. Today's report marks the first time TALENs have been used to edit mitochondrial genes.
Using cells in the lab, the investigators designed mitoTALENs to bind and cut mitochondrial DNA that had a specific mutation in the gene Complex I, which causes LHON. The scientists then tested whether the mitoTALENs eliminated the mutant mtDNA. Analysis revealed a temporary drop in cells' total mtDNA, which was due to a reduction in mutant mtDNA. "Once the mitoTALENs bound and cut the DNA at the specified target, the mutant mtDNA was degraded. The drop in total mtDNA stimulated the cells to increase their mtDNA by replicating the unaffected molecules. Two weeks later, mtDNA levels had returned to normal. But since the mutant mtDNA was destroyed, the cells had mostly normal mtDNA. A modest reduction in mutant mtDNA is likely sufficient to effectively treat disease."