CRISPR Pioneers Bag 2020 Nobel Prize in Chemistry
By Ruchi Jhonsa, Ph.D.
The Nobel Prize in Chemistry for the year 2020 has been jointly awarded to two female scientists who made one of the most monumental discoveries in the history of biology by developing a tool that could precisely edit the genome of everything from plants to animals. The award goes to Jennifer Doudna of the University of California, Berkeley, and Emmanuelle Charpentier of Max Planck Unit for the Science of Pathogens for the “development of a method of genome editing.”
CRISPR, which is short for clustered regularly interspaced short palindromic repeats, was first found in bacteria as a protective mechanism against viruses. In 2005, Francisco Mojica discovered that bacteria have disparate repeat sequences with a commonly shared set of features that helped them fight viral infection. Just like human immunity, bacteria remember previous viral infections by storing a copy of the viral genome between the repeat sequences. If the same virus invaded again, these stretches of DNA would recognize the virus and splice its genetic material. At the same time, a protein that helped bacteria chop the viral genome was discovered.
While the function of CRISPR was understood, its mechanism remained elusive up until 2008 when John Oost from the University of Wageningen, Netherlands, discovered that sequences derived from viruses turned into RNA and drove Cas9, the DNA chopping protein to the target DNA. These RNA sequences were termed as crRNAs.
The entire CRISPR mechanism became much clearer in 2011 with the final piece to the puzzle discovered by Emmanuelle Charpentier, who was working at the University of Vienna at the time. She found another piece of RNA called trans-activating CRISPR RNA (tracrRNA) that formed duplex with crRNA to bring Cas9 to its destined target.
While Jennifer Doudna was following the discoveries of various scientists in the field and making her contributions as a structural biologist, she got absorbed in the process when she decided to collaborate with Emmanuel to understand CRISPR better. The two scientists figured out how crRNA and tracrRNA join together with Cas9 to cut DNA at a specific site. They also found that the two RNA pieces could be combined into one guide RNA and still function. At this moment, a significant discovery was made when the duo realized that this defense mechanism could be used to edit genomes and not just kill viruses. The pair demonstrated this mechanism outside the cell by mixing the necessary ingredients.
Their discovery was rapidly expanded in many other systems and was taken up by Feng Zhang from the Broad Institute of MIT and Harvard and George Church from Harvard University to edit genome inside the mammalian cells. For the first time, the scientists demonstrated that CRISPR could work inside the mammalian cells and edit genome in the desired fashion. Dr. Doudna later demonstrated this phenomenon in mammalian cells confirming the findings of Dr. Zhang and Dr. Church.
Genome editing was not new at the time; however, with the discovery of CRISPR, it became much easier to edit the genome. Since its development as a gene-editing tool, CRISPR has become a household name and has benefited various disease areas. So much so, this year, CRISPR was used for the first time in humans to correct childhood blindness.
Earlier this year, both scientists also bagged the 2020 Wolf Prize in Medicine.
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