Washington: By borrowing a tool from bacteria that infect plants, researchers have developed a new approach that can be used to treat a variety of mitochondrial diseases, including the degenerative eye disease Leber hereditary optic neuropathy (LHON).
Searching for strategies to repair mitochondrial gene defects, a group of investigators at the University of Miami Miller School of Medicine explored proteins called transcription activator-like (TAL) effectors- which are found only in certain types of plant-infecting bacteria.
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 effectors 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.
Using cells in the lab, the investigators designed Mitochondrial-targeted TALENS (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.
Principal investigator of the study, Carlos T. Moraes, Ph.D, said that reducing but not necessarily eliminating all mutant mtDNA from a person`s cells would be sufficient to treat many mitochondrial diseases.
Mutant mtDNA typically does not cause signs of disease until it makes up 80 percent or more of the total mtDNA in a cell, which helps explain why age of onset, the constellation of symptoms, and disease severity varies among individuals with the same mutation.
The research is published in journal Nature Medicine.