13 October 2021

Not CRISPR-Cas9 unified

A new revolution in genome editing is coming

XX2 century

Over the past few years, scientists have adapted the CRISPR system, originally used by bacteria and archaea to protect against phages, to a variety of tasks: with its help, they create new varieties of crops, improve animal husbandry technologies, treat rare genetic diseases, they will probably soon treat HIV, and if they are lucky, they will even revive a mammoth. Now, researchers have discovered a new class of programmable DNA modification systems called OMEGA (Obligate Mobile Element Guided Activity).

Article by Altae-Tran et al. The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases is published in the journal Science.

These ancient DNA-cutting enzymes are guided to their targets by RNA, as are CRISPR-associated protein products. At the same time, according to the researchers, such systems of RNA-controlled enzymes (endonucleases) they turned out to be extremely common, and the famous CRISPR-Cas9 is only a special case of them. This discovery introduces us to a huge new field of biology and probably leads to another revolution in genome editing technology.

Recall that CRISPR-Cas9 is a natural system by which bacteria and archaea are protected from infections. She is able to embed a part of the viral genome into herself and then, using this part as a sample, very accurately cut out viral sections from bacterial DNA, thus preventing the replication of viral particles in the bacterial cell. At the same time, the CRISPR-Cas9 system can be "fed" almost any piece of genetic information, thus programming the "genomic scissors" to cut out a specific part of the genome.

It was assumed that evolutionarily CRISPR-Cas9 originates from transposons. The authors of the new work, a group of researchers led by MIT Professor Feng Zhang, conducted an evolutionary analysis, reconstructing the evolution of CRISPR-Cas9 from IS200/IS605 transposons, and found that IscB proteins, like CRISPR-Cas9, use non-coding RNA for controlled cutting of double-stranded DNA and, thus, can be used for programmable genome editing. Scientists have also demonstrated a similar mechanism for another protein, TnpB. The researchers, as already mentioned, called the open set of "genomic scissors" OMEGA systems. And, apparently, now we are waiting for a lot of research and development of new ways of programmable editing of genetic information. Zhang's research group also intends to investigate the evolutionary origins of RNA-controlled systems in general in order to get closer to understanding the basics of this mechanism.

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