Researchers at the University of Copenhagen (UCPH) have characterised and analysed the unique architecture of one of the most complex CRISPR-Cas systems known to date.
Within the past decade, CRISPR-Cas9 technology has revolutionised genome engineering and been at the forefront of research due to its potential applications in gene editing for hereditary diseases.
CRISPR is a system that was adapted from a genome editing system that naturally occurs in bacteria. The ability to re-engineer the bacterial enzyme Cas9 was first developed in 2012 by Professor Jennifer Doudna from the University of California and Professor Emmanuelle Charpentier from the Max Planck Institute for Infection Biology. Since then it has been adopted in several tools to manipulate DNA.
A study published in Molecular Cell by researchers at UCPH mapped and analysed a complex called Cmr-β, which belongs to the subgroup of type III-B CRISPR-Cas complexes. The structure was revealed using cyro-electron microscopy (cyroEM), a high-powered imaging technique. Using this technique, the researchers were able to capture the complex during different conformational stages of the immune response. The researchers were able to study the role of this complex in the immune system and demonstrated the diverse defence mechanisms of this complex against invading genetic elements, including single-stranded DNA cleavage and cyclic oligoadenylate synthesis. In particular, the researchers identified a unique subunit called Cmr7, which appeared to control the complex activity.
Although the system is too large and intricate to be used for gene editing like CRISPR-Cas9, understanding its mechanisms will hopefully provide further insight into the immune response of bacteria. This could prove useful in the fight against antibiotic resistance.
Guillermo Motoya, co-author and Professor at Novo Nordisk Foundation Center for Protein Research, UCPH, stated:
“The complex may also have therapeutic potential. In the future, we may be able to use this for diagnostics or a health problem we may not even have seen yet. Now, our goal is to look for an application for this system.”