12 December 2016

CRISPR Protection

Geneticists have learned how to embed protection against gene modifications in the DNA of cells

RIA News

Biologists from the USA and Scientists have discovered an unusual family of proteins that viruses use to protect themselves from cellular "antivirus" and which can be used to protect cells and whole organisms from editing their DNA, according to an article published in the journal Cell (Pawluk et al., Naturally Occurring Off-Switches for CRISPR-Cas9).

"We weren't even trying to find protection against CRISPR, we were just trying to understand how phage viruses insert themselves into bacterial genomes. As a result, we came across something that I think will be very important for the further development of biotechnology. Such a CRISPR "switch" will allow us to control where, how and when we will edit DNA," said Alan Davidson from the University of Toronto (Canada).

The CRISPR/Cas9 genomic editor, called the main scientific breakthrough of 2015, was created by American scientist Feng Zhang and a number of other molecular biologists about three years ago, and since then it has undergone several upgrades that allow scientists to use it to edit the genome with absolute accuracy.

In fact, CRISPR/Cas9, like many other things, was invented not by man, but by nature – initially this system developed inside bacteria hundreds of millions of years ago to protect against retroviruses, and only in 2012 Feng Zhang and his colleagues adapted it for editing the genome of multicellular creatures. It consists of two components – a "library" of samples of the genetic code of viruses (CRISPR), and the Cas9 enzyme, which searches for similar sequences in the DNA of a bacterium and removes them if necessary.

Davidson and his colleagues found that viruses did not stay away from this "bio-arms race" and created their own response to CRISPR/Cas9 – a set of three proteins that cling to different parts of the Cas9 protein and neutralize it even before it has time to cut the DNA of the virus from the genome of the microbe.

These proteins were discovered, as Davidson says, completely by accident. His scientific team observed how different versions of bacteriophage viruses penetrate the cells of meningococci (Neisseria meningitidis) - pathogens of meningitis that actively use CRISPR/Cas9 to protect themselves from viruses.

It turned out that some bacteriophages contain three previously unknown proteins – acrIIC1, acrIIC2 and acrIIC3. These proteins, as further experiments have shown, can attach to Cas9 molecules and neutralize them, preventing them from recognizing viral DNA or RNA and destroying it.

When scientists isolated the genes responsible for the production of these proteins and inserted them into human cells, this made the DNA of these cells "protected" from overwriting – all further attempts to make changes to the genetic code using CRISPR/Cas9 were stopped by bacteriophage proteins.

Drawing from an article in Cell – VM

What is interesting about this discovery? It means that scientists have finally got a way to flexibly control how and where genome editing will be performed using the CRISPR/Cas9 system. This will make it possible to create safe types of gene therapy for the treatment of congenital diseases, to make GMOs "clean" from the point of view of genetics, and to implement many other things that could not be done due to the fact that scientists did not know how to control the work of this genomic editor.

In addition, from an evolutionary point of view, the discovery of the DNA "anti–editor" explains the following riddle - if the CRISPR/Cas9 system is so effective, then why did the viruses not die out? As it turned out, viruses coped with the challenge of bacteria by responding to the creation of a biological "antivirus" by discovering molecules that suppress its work.

Portal "Eternal youth" http://vechnayamolodost.ru  12.12.2016

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