Nobel Prize 2020 in Chemistry honors CRISPR: a tool for rewriting the code of life
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COMMENTARY
Nobel Prize 2020 in Chemistry honors CRISPR: a tool for rewriting the code of life Lukas Westermann 1 & Björn Neubauer 1 & Michael Köttgen 1,2 Received: 10 November 2020 / Revised: 10 November 2020 / Accepted: 20 November 2020 # The Author(s) 2020
Emmanuelle Charpentier and Jennifer Doudna have been awarded the 2020 Nobel Prize in Chemistry for their work on CRISPR-Cas9—a method to edit DNA. The two scientists were recognized by the Nobel Committee for their discovery that a microbial immune mechanism can be transformed into a tool that can simply and cheaply edit genomes with high precision. In the seven decades since the discovery of the DNA double helix, technologies for analyzing, manipulating, and making DNA have enabled considerable advances in biological research [3]. But site-specific modifications of genomes remained challenging. Previous genome editing tools such as zinc-finger nucleases (ZFN) and transcription-activator– like effector nucleases (TALEN) highlighted the potential of targeted manipulation of genes, but limited targeting capacity and complicated design hampered the usability of these technologies [3]. CRISPR-Cas9 can be considered a real game changer due to its simplicity and efficiency. CRISPR stands for clustered regularly interspaced short palindromic repeats and is used by bacteria to fight phage infections. In principle, the CRISPR system enables bacteria to recognize genetic sequences of invaders and target these sequences for destruction using specialized enzymes. These enzymes are called CRISPR-associated proteins (Cas) and include the DNA endonuclease Cas9 [8]. In 2011, Charpentier’s group identified a key component of the CRISPR system, an RNA molecule that is involved in recognizing foreign phage sequences in bacteria, so-called transactivating crRNA (tracrRNA) [1]. A subsequent collaboration of the Charpentier and Doudna laboratories resulted in the * Michael Köttgen [email protected] 1
Department of Medicine, Renal Division, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
2
CIBSS – Centre for Integrative Biological Signalling Studies, Freiburg, Germany
landmark 2012 Science paper, which kick-started the era of CRISPR-Cas9 genome editing [6]. The paper showed that a bacterial CRISPR-Cas9 endonuclease is guided by two RNA molecules forming the tracrRNA:crRNA duplex, to direct site-specific DNA cleavage. Importantly, it was shown that the dual tracrRNA:crRNA can be engineered as a single guide RNA (sgRNA) that retains two critical features: a 20 nucleotide sequence that determines the target site and a doublestranded structure that binds to Cas9. This created a simple two-component system in which changes to the 20 nucleotide guide sequence can be used to target CRISPR-Cas9 to virtually any DNA sequence of interest [3, 6]. Gene function can be disrupted by CRISPR-Cas9mediated induction of double-strand breaks followed by nonhomologous end joining repair or gene replacement by homology-directed repair. Thus, we c
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