The Mayo Clinic (Rochester, USA) has developed a method that allows, at the request of the researcher, to turn on and off any gene in a living organism.
The existing methods of genome control are built according to the same scheme, which seriously limits their application: we are talking about suppressing gene activity.
The easiest way to do this is by cutting the DNA with this gene with an enzyme so that even after repair, the gene cannot function. For this, nucleases with so-called zinc fingers are used - structural elements that have specificity for one or another nucleotide sequence.
But the set of such "zinc fingers" is limited, that is, not every fragment in DNA can be detected with their help. Morpholine oligonucleotides are an alternative. These are short synthetic nucleotide chains with absolutely any specificity you can desire. By attaching to cellular DNA, they block the activity of a particular gene. The disadvantage of this approach is temporary action: sooner or later, the blockade from the gene will be lifted by itself.
In an article published in the journal Nature, the authors describe a third method based on the use of TALEN (Transcription Activator-Like Effector Nuclease) nuclease enzymes. These are hybrid proteins, some of which are taken from bacteria. The bacterial fragment binds to small fragments of DNA; due to its extraordinary variability, it can be adapted to recognize almost any DNA sequence. Another piece of the TALEN molecule is the nuclease itself, which makes cuts in DNA.
Until now, TALEN have been used in cell cultures. Now researchers have been able to adapt this method to whole organisms. A genetic regulator was inserted into the genome of the striped zebrafish (Danio rerio) that allowed a specific gene to be turned on or off. That is, using the specific nuclease TALEN, an incision was made near the gene of interest to scientists. Then, this regulatory nucleotide sequence was inserted into the incision using other enzymes.
After that, all that remained was to press the lever, that is, to add substances that turned the regulator on or off. It should be emphasized that, firstly, the use of TALEN allows the introduction of a regulatory sequence "sideways" to any gene, and secondly, this manipulation, as the authors have shown, can be carried out with the whole organism, and not only with the cell culture.
It is difficult to overestimate the prospects of a new method (or a new modification of an old one, if you like). For example, it is important to know what a particular gene does throughout life, whether its function changes, whether it continues to work, etc. Until now, it was incredibly difficult to find out: scientists could turn off some gene for another stage of the embryo, but it was not possible to turn it back on in an adult organism. If the mutation turned out to be critical, the embryo died, after which it was concluded that the gene was extremely important at the embryonic stage, but no one knew what happened to it next.
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And now there is a chance to thoroughly learn the age-related, so to speak, features of the work of genes. And this is not to mention the fact that with the help of the described method, it is theoretically possible to “turn on” or “turn off” genes, the wrong activity of which is the basis of severe hereditary (and not only hereditary) diseases.