A new gene-editing technique holds immense promise for the treatment of mitochondrial-DNA linked diseases.
A new development in gene-editing has sparked hope for the treatment of genetic diseases that even the revolutionary CRISPR Cas9 system couldn’t help cure. Nature reports that a research team led by Joseph Mougous at the University of Washington, in 2018, discovered an enzyme—DddA—produced by the bacterium Burkholderia cenocepacia that has a rather remarkable effect; when it comes across the pyrimidine cytosine (C), it changes it into the pyrimidine uracil (U). Given U is not commonly found in DNA, and behaves like the pyrimidine thymine (T), in DNA replication, it gets copied as T, which means the original C is converted into a T. While CRISPR Cas9 also relies on base editing, it relies on an RNA strand to guide the Cas9 enzyme to the region of the DNA that the researchers wish to edit—this is fine for editing genes in the nucleus, but the mitochondria is a different deal.
However, Mougous’s team found that DddA acts on double-stranded DNA without need Cas9 to break the DNA. David Liu, of Broad Institute of MIT and Harvard, and Mougous, worked on splitting DddA to control its base-changing effect for super-precision, instead of indiscriminate C to T conversion.
Though it is still a long way from clinical use, as the researchers who developed it have cautioned, the technique holds immense potential for research and even treatment of mitochondrial-DNA mutations that manifest as maternally-inherited conditions. Though the mitochondrial genome is considerably smaller than the nuclear genome, mutations in this have grave pathological consequences on the nervous system and muscles, including cardiac muscles. While the technique needs much more refinement, it is undoubtedly a breakthrough that can change the future for those suffering from several cardiomyopathies and encephalopathies.