Leaving Italy

What is CRISPR/Cas9?

This week I decided to postpone my last post of the year by a couple of days, so that I could wrap up this very though year for me by talking about what I consider one of the greatest discoveries of the century. Indeed, after a serie of unfortunate events (that seem to come one after another this year), I was forced to spent the entire day at home yesterday and I caught up with the Italian news. By chance, like most of the events that are out of my control this year, I came across the news that the Chinese scientist, who genetically engineered three babies, got 3 years in prison (if you are interested, have a look at the article here). As my post on CRISPR/Cas9 was already planned, I decided to add this brief digression to underline how great ideas carry huge advantages that can improve humankind health and wellbeing, as well as shadows that can obscure all these pros.

“If you change the way you look at things, the things you look at change.”Wayne Dyer

As I have already written in my previous post last week (have a look here if you missed it), bacteria have always been very important to humankind and I had the chance to appreciate their usefulness in research during my time in York (UK). I did not use any particular new technique, but already being able to insert DNA into bacterial cells and making them produce my protein of interest tagged with a green-fluorescent marker got me incredibly fascinated. Unfortunately, my time in York was limited to one year and I did not have the chance to set this new technique up in my lab, but I got amused by this system called CRISPR/Cas9 and today I will briefly present to you the mechanism behind it and its potentialities.

The CRISPR/Cas9 system is based on the use of the protein Cas9, a kind of molecular scissor that is able to cut a target sequence of DNA. After the genome is cut, it is possible to delete, substitute or modify these DNA sequences that, for example, are carrying dangerous mutations for our health. The programming of the Cas9 target is done via a molecule of RNA (complementary to the target sequence of DNA), called guide RNA (gRNA), that can be easily produced and modified in a lab, and, once associated to Cas9, it acts like a leash, anchoring the Cas9 protein to the target DNA (have a look below for a schematic of its mechanism).

Schematic of the CRISPR/Cas9 mechanism. From cambridge.org

This system was identified in bacteria, where the Cas9 protein protects these microorganisms against pathogen viruses, acting like a bacterial immune system. Between 2012 and 2013 two research groups from the states (Berkeley and MIT) were the first that demonstrated how this technology can be borrowed from bacteria and applied as a biotech instrument to cut specific DNA sequences inside the genome of non-bacterial cells.

This discovery was a revolution for the biomedical research, since for the first time it was possible to introduce in the genome the desired modifications in a simple, effective, fast and economic way. Indeed, in few years, CRISPR/Cas9 reached labs all over the world and it is used for both basic and applied research: even if it is a relatively new system, thanks to its robustness and reproducibility, its application is rapidly going towards the clinical research.

In the right experimental settings, this system can be used to introduce the desired changes with a precision that has never been seen before in the history of genetic engineering. The CRISPR/Cas9 technology con introduce point mutations (where a single nucleotide base is changed, inserted or deleted from a sequence of DNA) that are indistinguishable from the natural occurring ones and that can silence a dangerous gene. Moreover, apart from correcting defecting sequences of DNA, it is even possible to insert new genes that can give an advantageous characteristic.

These tricks are becoming incredibly useful for the basic research, since they allow, for example, to investigate the molecular basis of genetic diseases. Furthermore, CRISPR/Cas9 works in all organisms -from bacteria to plants and humans- and the possible applications are limitless. Among the most promising research areas in biomedicine there are new drugs development, genic and cellular therapies, xenografts and insect-borne diseases.  Finally, there are great hopes for industrial applications, as the genomic editing might favor the development of useful products such as a new class of biofuels.

All these different applications have many advantages, but also risks and ethical considerations (as the aforementioned case of the Chinese scientist) that should always be evaluated carefully case by case.

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