Not that long ago, the acronym CRISPR (which stands for “Clustered Regularly Interspaced Short Palindromic Repeats”) was only meaningful to a small group of microbiologists studying bacterial immunity. That changed virtually overnight with the publication of seminal papers describing how this molecular tool could be used for gene editing. Less than a decade later, the 2020 Nobel Prize in Chemistry was awarded to the two pioneers of CRISPR genome editing — Emmanuelle Charpentier (Max Planck Institute, Germany) and Jennifer Doudna (University of California, Berkeley).
The role of CRISPR in bacteria is to protect them from bacteriophage infections. When the viral DNA enters a bacterial cell, it is recognized by a complementary short RNA fragment known as the guide RNA (gRNA). The gRNA forms a complex with a bacterially-encoded CRISPR-associated (Cas) nuclease, which then cuts the identified viral DNA segment and kills the virus.
The real breakthrough in CRISPR technology came from figuring out how to use this mechanism to target any DNA sequence in the genome. It stemmed from a collaboration between Charpentier, who was studying the Streptococcus pyogenes CRISPR-Cas system, and Doudna, who combined the native CRISPR RNA (crRNA) and trans-activating RNA (tracrRNA) molecules into one synthetic single-guide RNA (sgRNA). The sgRNA could now be synthesized and expressed to target almost any genomic sequence for cutting [1].
Soon after, Feng Zhang’s lab (Broad Institute of MIT and Harvard) demonstrated that CRISPR-Cas systems in combination with homologous recombination could be used as a programmable gene-editing tool. The group achieved precise editing in mammalian cells by providing a repair template with the desired edit along with the guide RNA and Cas enzyme [2].
Over the years, CRISPR editing has been demonstrated in a large variety of organisms, from plants to human cells, and evolved into a number of new applications, such as transcriptional repression or base editing. Alternative Cas nucleases have been discovered and adopted by researchers to enhance the performance of CRISPR editing.
It took less than a decade from the first CRISPR editing publication to the Nobel Prize in Chemistry award, making history as the invention that took the shortest time to be recognized by the Nobel Committee.
But this discovery did not take place in isolation – there were decades of research and technological breakthroughs in other disciplines that allowed the CRISPR discovery to evolutionize genome engineering. We acknowledge these efforts and celebrate the collaborative nature of the CRISPR story.