Nobel Prize in Chemistry 2020: The great breakthrough from frontier research in microbiology

Abstract

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer A. Doudna for their joint development of the highly efficient CRISPR-Cas9 genome editing tools, which have taken the life sciences into a new era. The CRISPR-Cas system was first discovered in bacteria in 1987. After more than 20 years of arduous exploration of these enigmatic systems that were found in more than 90% archaea and about half bacteria, their antiviral function was finally confirmed in 2007. This has inspired more researchers to focus on the CRISPR-Cas systems, of which the general anti-virus mechanisms were also uncovered within the next few years, that the crRNA containing the virus sequence information guides the Cas protein(s) to recognize the corresponding virus and cleave their DNA or RNA. Among those pioneers in this field, Charpentier and Doudna mainly focused on the type II CRISPR-Cas9 system, which is much simpler than the wide-spread type I systems. In 2012, Doudna and Charpentier had elucidated the fine structure of the anti-virus effector complex of the CRISPR-Cas9 system, which contains a single Cas9 protein and two RNA components (crRNA and tracrRNA). It was this work that led to the breakthrough in developing the CRISPR-Cas9 genome editing tools. Significantly, they innovatively connected the tracrRNA and crRNA into a single RNA chimera (sgRNA), greatly simplifying the genome editing tools to only two components, the sgRNA and the single Cas9 protein. Compared with the genome editing tools developed in the past (Meganuclease, ZFN and TALEN), CRISPR-Cas9 has significant advantages such as easy programming, high efficiency and a wide application range. These merits make CRISPR-Cas9 so far the most widely used genome editing technique. In basic research, CRISPR-Cas9 genome editing has been used to elucidate the functions of unknown genes or pathways. In application, this technique has greatly improved the efficiency of animal and plant breeding, and made it possible to cure some genetic diseases and even cancers. Moreover, based on this CRISPR-Cas9 platform, other advanced genome editing tools have also been developed, such as base editing and prime editing, etc. It is also believed that, in addition to CRISPR-Cas systems, there are still many other undiscovered antiviral systems in microbes, as well as a large number of unknown nucleic acid recognition and processing elements, which are expected to optimize or upgrade the current genome editing tools, or even innovate entirely new genome editing tools. The CRISPR-Cas genome editing tools were developed from the bacterial anti-virus immune systems, thus the 2020 Nobel Prize in Chemistry is essentially a reward to the frontier research in microbiology. In this article, we will briefly introduce i) the timeline for the development of genome editing tools; ii) the historical background of the CRISPR-Cas research; iii) the breakthrough works for the birth of CRISPR-Cas9 genome editing technology. The future frontier research in microbiology and big data mining to further optimize or innovate genome editing tools is also prospected.