The MAGESTIC system perfects the CRISPR-Cas9 genetic manipulation system

An illustration of the MAGESTIC system (Image courtesy Kelly Irvine/NIST. All rights reserved)
An illustration of the MAGESTIC system (Image courtesy Kelly Irvine/NIST. All rights reserved)

An article published in the journal “Nature Biotechnology” describes a new refinement of the CRISPR-Cas9 genetic technique. A team of researchers of the Joint Institute of Metrology and Biology (JIMB) developed a system called MAGESTIC that was compared to the search-and-replace function of a word processor with respect to a blunt cutting tool.

The CRISPR (clustered regularly interspaced short palindromic repeats) acronym refers to prokaryotic DNA segments containing short repeated sequences. The expression CRISPR/Cas refers to a prokaryotic immune system conferring a genetic resistance to foreign elements. The CRISPR/Cas system is used in genetic engineering, in particular using the Cas9 (CRISPR associated protein 9) enzyme, that evolved in bacteria of the species Streptococcus pyogenes as part of their immune system.

CRISPR techniques are already being tested in various fields, including the medical field to eliminate genetic diseases that can be even lethal. However, their development was accompanied by discussions about possible problems that could accompany their use. More specifically, after a genetic intervention, the organism’s DNA repair process is started and sometimes it has imperfect results with possible side effects.

Various researches are trying to assess the risks associated with the use of CRISPR techniques, but in the meantime other studies continue to improve them. One of these examples is given by a genetic modification system developed by JIMB, a collaboration between Stanford University and the American National Institute of Standards and Technology (NIST).

This new version of the CRISPR-Cas9 technique was called “multiplexed accurate genome editing with short, trackable, integrated cellular barcodes” (MAGESTIC). Tests were carried out on Saccharomyces cerevisiae, commonly known as budding yeast.

One of the key features of the MAGESTIC technique is the use of a new type of “cellular barcode” built into the chromosomes as a guide. A protein called LexA-Fkh1p is used to recruit the right bases and use them directly in the position where the cut was made on the DNA.

The original technique has the problem of having to search through millions if not billions of base pairs for the right one for DNA repair after the modification. With the MAGESTIC technique, that genetic barcode is integrated directly into the DNA of the cell, in this case the yeast, to obtain a much quicker and more precise tracing.

The researchers carried out a series of tests of the MAGESTIC system, verifying that it works correctly. As always happens for this type of research, the analysis of the results continues to verify the presence of possible mutations. Further development will come from the use of this system for more in-depth genetic studies with the introduction of different variants and the analysis of their consequences.

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