Most cells in the human body have two genetic libraries; one in the nucleus and the other inside structures called mitochondria.
The collaborative efforts of several research groups have led to a process that will one day allow scientists to change the instructions that make up the “other” genome of a cell and potentially treat a range of diseases.
The molecular basis for this revolutionary gene editing tool is the DddA toxin secreted by the bacterium Burkholderia cenocepacia to kill other microbes when competition for resources becomes severe.
Researchers at the University of Washington have been interested in the toxin for a while, discovering that it converts a nucleic acid base called cytosine into another one commonly found in RNA called uracil.
This isn't the first time researchers have turned to bacterial weapons for clues on how to tune DNA in this way. In fact, a whole family of so-called deaminase enzymes have already been used in genetic engineering.
A research team at MIT has combined deaminase with code exchange with CRISPR technology, which entails using an RNA template to identify the sequence and then using enzymes to make changes.
This isn't too much of a problem if you want to make changes to duplicate DNA strands inside something as welcoming as the nucleus of a cell. But changing RNA templates across the selective mitochondrial membrane is not easy.
This is due to the fact that more than a billion years ago, mitochondria were organisms themselves, and over time they have evolved, sharing the responsibility of breaking down glucose with cells.
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Fortunately, the DddA toxin had the unique ability to alter both strands of DNA, paving the way for CRISPR - and its cumbersome RNA template - in favor of alternative methods of targeting the sequence you want to change.
This class of enzymes can be adapted to search for specific nucleic acid codes and their separation. Just what is needed for the introduction of a toxin that replaces cytosine.
Together with DddA, a specially designed enzyme can find the target sequence within the mitochondria and convert any cytosine it finds into uracil, which is subsequently transformed into a similar DNA-specific backbone called thymine.
Just as mutations in nuclear DNA can cause a wide variety of health conditions, mutations in mitochondrial genes can also be problematic, affecting anything from brain development to muscle growth, energy levels, metabolism, and immunity.
The research is published in the journal Nature.