An article published in the journal “Nature Methods” reports the results of the experimentation of a variant of the CRISPR-Cas genetic technique, in recent years used a lot in some variants for genetic manipulations of different types. A team of researchers at ETH Zurich, Switzerland, used the Cas12a enzyme to achieve a significant step forward in this type of technique because it enables to intervene on up to 25 genetic sites simultaneously.
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 Cas12a (CRISPR associated protein 12) enzyme, which is actually another name for the Cpf1 announced in 2015, comes from various bacteria such as a strain of the genus Acidaminococcus or a strain of a bacterium from the Lachnospiraceae family and the former version was proved more efficient than the latter. This version of the enzyme, also referred to as AsCas12a to distinguish it from the version obtained from the other bacterium, proved to be more flexible than the Cas9 enzyme, the one most widely used among the CRISPR-Cas variants, due to its ability to operate on DNA and RNA at various sites with an intervention. The variants used so far can generally make changes to only one gene, on occasion to two or three genes simultaneously and on one occasion scientists were able to modify seven genes simultaneously.
Professor Randall Platt and his team developed a process based on the Cas12a enzyme that in experiments made it possible to modify 25 sites within a cell’s genes at once. That isn’t the highest possible number but can be increased even to hundreds of genes offering an enormous potential for biomedical and biotechnology research.
The image (Courtesy ETH Zurich / Carlo Cosimo Campa. All rights reserved) shows genes in the form of dots and interactions between genes and proteins in cells in the form of lines. A complex system of interactions controls gene replication and expression and the CRISPR-Cas technique that uses the Cas12a enzyme makes it possible to hack that system.
From the beginning, the Cas12a/Cpf1 enzyme proved it was promising, showing greater precision than Cas9. Over time researchers also explored its flexibility, which is now fully revealed by Professor Randall Platt’s team. However, these are delicate interventions and further experiments are needed to adequately control its use but the first tests to eliminate genetic diseases are already underway and this version of the CRISPR genetic technique may be a more sophisticated tool in medical research and more.
