Scientists first find a way to make targeted changes to DNA

(ORDO NEWS) — Most cells in the human body have two genetic libraries; one in the nucleus and the other inside structures called mitochondria.

The combined efforts of several research groups led to a process that once allowed scientists to change the instructions that make up the “other” cell genome and potentially treat a number of diseases.

The molecular basis of this revolutionary gene editing tool is the DddA toxin, secreted by the bacterium Burkholderia cenocepacia to kill other germs when competition for resources becomes serious.

Researchers at the University of Washington for some time were interested in the toxin, discovering that it converts a nucleic acid base, called cytosine, into another, usually found in RNA, called uracil.

This is not the first time that researchers have turned to bacterial weapons to find clues on how to tune DNA in this way. In fact, a whole family of so-called deaminase enzymes has already been used in genetic engineering.

A research team from the Massachusetts Institute of Technology combined deaminase with code exchange with CRISPR technology, which entails using an RNA matrix to identify the sequence, and then using enzymes to make the change.

This is not a big deal if you want to make changes to double the strands of DNA inside something as welcoming as the cell nucleus. But changing RNA templates across a selective mitochondrial membrane is not so simple.

This is due to the fact that more than a billion years ago, mitochondria themselves were organisms and evolved over time, sharing the responsibilities of splitting glucose with cells.

Fortunately, the DddA toxin had the unique ability to modify both DNA strands, paving the way for CRISPR – and its bulky RNA matrix – 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 you need for the introduction of a toxin that replaces cytosine.

Together with DddA, a specially created enzyme can find the target sequence inside the mitochondria and turn any cytosine found by it into uracil, which is subsequently transformed into a similar DNA-specific base called thymine.

Just as mutations in nuclear DNA can cause a 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.


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