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A month ago, Prof. Emmanuelle Charpentier & Prof. Jennifer Doudna were awarded the Nobel Prize in Chemistry. They are just the sixth and seventh women who have been awarded the prize in this category. They won the award for the invention of the most unique genome editing tool known as CRISPR (Clustered Regularly Interspaced Palindromic Repeats)! Indeed such a monumental achievement made them the only women duo who has won the award! Keep reading to find out more about how this invention came about.

An ancient virus-fighting tool found in bacteria

I’m sure we’re all wondering what exactly CRISPR is and what the hype is about. The first time such a set of genomic sequences were discovered was in the year 1987. It was observed in a bacterial species known as Haloferax mediterranei where they found a set of perfect palindromic sequences. However, upon further bioinformatic analyses, it was discovered in many other prokaryotic species but its function was still unknown!

More studies into the function led to the discovery of the fact that any of the proteins that are encoded by the Cas genes, were involved in the DNA expression & metabolism. Later, in the year 2005, the actual function of these sequences was discovered. Finally, it was found that the species had these sequences, seemed to be protected from any kind of infection especially viral ones. Immediately, they realized that the complex that was formed, had the ability to target any invading nucleic acid sequences, and cleave them! Besides that, they had additional mechanisms against any kind of interference!

The process of CRISPR based adaptive immune system in bacteria
The process of CRISPR based adaptive immune system in bacteria (Source: nobelprize.org)

Consequently, more experiments in the bacterial species Streptococcus thermophilus only confirmed these findings. Even when the space region containing the CRISPR sequences were removed, they lost their ability to fight off any infection. This was one of the greatest discoveries at the time.

Discovery of the CRISPR-Cas9 system

By the end of 2011, the three functions of Cas proteins had become clear. They could integrate any new sequences into CRISPR loci; create more RNA sequences that performed these functions and stop any organism from invading their cells. But how did the shift from defense to genome editing come about?

It was only when experiments in the Streptococcus species were done, they figured it out. Using inactivation studies for different components, each of their functions was detailed. What was interesting is that they found that the Cas proteins were more than enough for propagating these interference mechanisms.

Applications of CRISPR-Cas9 genome editing

Years of studies on these bacterial species and the unique system that they possess has really changed the way in which it can be applied. As they uncovered the intricacies of each of the components, they soon realized this can be applied for editing genomes as well. It’s simple. They isolated each of the components and tried similar reactions in a test tube. Much in the way the Cori cycle was discovered, really.

The process of CRISPR-Cas9 based genome editing
The process of CRISPR-Cas9 based genome editing (Source: nobelprize.org)

They fused different components to form a single guide RNA that can specifically target the sequences they’d like, and cleave them. By doing so, the DNA segment can be cut at whichever point they’d want to. Any great discovery must first be proved in in vitro analysis and that’s what they did. Soon, this sparked hundreds of gene editing experiments that led to the identification of many applications in science.

The fact that they took an ancient protection mechanism and converted it into one of the most innovative tools in the 21st century was incredible. It goes to show how a scientist’s intuitiveness can go a long way and why creativity is still paramount in the field of sciences. Needless to say, the impact of this invention will be felt decades later. This is because more avenues open up in both basic and applied biological sciences.

References

A tool for genome editing (2020). Retrieved from https://www.nobelprize.org/uploads/2020/10/advanced-chemistryprize2020.pdf

Ledford, H. & Callaway, E. (2020). Pioneers of revolutionary CRISPR gene editing win chemistry Nobel. Retrieved from https://www.nature.com/articles/d41586-020-02765-9

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