A cutting-edge gene editing system discovered by scientists

Gene editing is a term that some of you might have across these days, isn’t it? It’s an important part in the study of human diseases, their preventions and cures, used in research laboratories to analyse cells and animal models. It is nothing but a group of technologies that help scientists alter the DNA or the genetic material of organisms by addition, subtraction or complete alteration in certain cases.  

Till date, many approaches of gene editing have been developed and one of most popular of them is the CRISPR system. It is a gene editing technology wherein certain bacteria use a defence system to protect themselves from bacteriophages or phages (viruses that specifically infect bacteria). How? By collecting DNA sequences from the phages in advance and creating Cas proteins (defence systems) that alter their DNA into RNA, creating a sense of duplicity for whoever attacks.  

Now, there are different kinds of CRISPR system. Cas9 for instance is well-known wherein as soon as any phage attacks the said bacteria, the DNA changes into RNA, which in turn immediately binds to the matching sequence in the phage’s DNA by cutting through both its sides. While this is quite advanced, a brand-new and more potent system known as Cas12a2, has been developed by CRISPR pioneers Jennifer Doudna and Jill Banfield alongside their team of researchers. They claim that it could help in developing the cure for drug-resistant infections and also enable scientists to control microbes without involving antibiotics.  

This system has been published as a paper titled “Broad-spectrum CRISPR-Cas12a2 enables efficient phage genome editing” in the journal Nature Microbiology and posits a milestone in the field of engineering bacteriophages and dealing with their genetic diversity. The study has been funded by the Department of Energy Microbial Community Analysis & Functional Evaluation in Soils (m-CAFES), USA. 

Okay, now coming back to bacteriophages, they are known to inject their genetic material into bacterial cells and then hijack the protein-building machinery of the bacteria that otherwise help in building a defence. This in turn results in the death of the host bacteria. Now, a CRISPR gene editing technology such as Cas9 usually warns the bacteria by inserting an RNA sequence that helps them identify their predator and attack them with killer enzymes. However, bacteriophages too have now learnt to invasively attack the bacteria, often making it difficult for the likes of Cas9 to help the hosts fight back. In other words, the phages have become resistant to systems like Cas9 or have simply got better in repairing themselves after counter attack. This is where the brand-new Cas12a2 comes into play.  

Turns out, it is engineered like a Swiss Army Knife, meaning, it activates as soon as it binds to its target, metamorphoses and can mould itself into any kind of genetic material that it encounters. This means that bacteriophages now will not be able to realise when and how they are being counterattacked, unless it’s too late. Sounds great, isn’t it? What’s even better is that, the new system is programmable, meaning it only kills toxic bacteriophage cells, leaving behind the healthy cells unharmed, that often have diagnostic potential.  

By chance if you were wondering how the researchers developed this tool, it was a mere accident while experimenting with a rare form of CRISPR called Cas12. While it didn’t lead anywhere yet, Cas12a2 was born out of the blue and is now being deemed as the future of gene editing and can possibly revolutionise the field. It can also aid in the domains of biomanufacturing, agriculture, food production and more.  

Encouraged by their latest success, the team is now looking to expand the CRISPR system more and working with phages such as the ones that affect microbial soil communities.