Remote control of the work of genes in an adult body

Is it possible to control other people's genes in real time?

Kirill Stasevich, CompulentaThe Mayo Clinic (Rochester, USA) has developed a method that allows the researcher to turn on and off any gene in a living organism.

The existing methods of genome management are built according to one scheme that seriously restricts their use: we are talking about the suppression of gene activity. The easiest way to do this is by cutting the DNA with this gene with the help of an enzyme so that even after repair this gene could not function. To do this, nucleases with so–called zinc fingers are used - structural elements that have specificity for certain nucleotide sequences.

One of the ways of specific interaction of proteins and DNA:
zinc fingers of the transcription factor (purple) "take" the DNA strand
(drawing by Laguna Design).

But the set of such "zinc fingers" is limited, that is, not every fragment in DNA can be detected with their help. An alternative is morpholine oligonucleotides. These are short synthetic nucleotide chains, with absolutely any specificity that you can wish for. 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 of the gene will be lifted by itself.

In an article published in the journal Nature (Bedell et al., In vivo genome editing using a high-efficiency TALEN system), the authors describe a third method based on the use of enzymes-TALEN nucleases (Transcription Activator-Like Effector Nuclease). 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 actually a nuclease that makes cuts in DNA.

So far, TALEN has been used in cell cultures. Now, researchers have managed to adapt this method to whole organisms. A genetic regulator was inserted into the genome of the striped danio (Danio rerio), which allowed turning on or off a specific gene. That is, with the help of a specific TALEN nuclease, an incision was made near the gene of interest to scientists. Then this regulatory nucleotide sequence was inserted into the incision with the help of other enzymes. After that, it remained only to press the lever, that is, to add substances that turned on / off the regulator. It should be emphasized that, firstly, the use of TALEN allows you to introduce a regulatory sequence "side by side" to any gene, and secondly, this manipulation, as the authors have shown, can be carried out with the whole organism, and not just with cell culture.

The prospects of a new method (or a new modification of the old method, if you like) can hardly be overestimated. 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 at the stage of the embryo, but it was impossible 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.

And now there is a chance to thoroughly learn the age, so to speak, features of the work of genes. And this is not to mention that with the help of the described method, it is theoretically possible to "turn on" or "turn off" genes whose incorrect activity underlies severe hereditary (and not only hereditary) diseases.

Prepared based on the materials of Nature News: Custom gene editing rewrites zebrafish DNA.

Portal "Eternal youth" http://vechnayamolodost.ru25.09.2012