This week, it was reported that the 2020 Nobel Prize in Chemistry has been awarded to Emmanuelle Charpentier and Jennifer Doudna for their research on the technology of genome editing -- more specifically, Crispr-Cas9. (See story on BBC News).

Scientists at the University of Warwick who work in the same field explain what Crispr-Cas9 is, and discuss its significance in our lives.

Dr Antonia Sagona:

"In agriculture, CRISPR-Cas9 is used to develop crops that are healthier and more resistant to pest and so has great implications in the overall economy.

"In medicine, the system can be used to provide treatment to various genetic diseases, infectious diseases and cancer, by the gene-editing of organs and human cells. Overall this system offers a very accurate and easy gene-editing method, with vast implications in health and economy.

"The CRISPR-Cas9 system originally was found in prokaryotes (bacteria) as a mechanism of adaptive immunity, for their protection against foreign DNA (from bacterial viruses that target specific bacteria, called bacteriophages).

"Cas9 is a gene-cutting molecule, which was found originally able to cut the DNA of bacteriophages and thus to protect the bacteria from getting infected from those. The CRISPR-Cas9 system uses a guide RNA to bind to a specific region in the DNA and the Cas9 protein cuts the DNA is defined regions, as a pair of genetic scissors. This system can be modified to cut very precisely any part of the genome and in this way it works as an excellent gene-editing tool. CRISPR-Cas9 allows scientists to change the DNA in any organism and as such, it is a significant tool with many applications in biology, agriculture and medicine.

"In biology, multiple labs around the world use this system for experimental purposes, to genetically modify organisms and provide those with the preferred genotype according to the experimental setting, such as bacteriophages, mice, Drosophila melanogaster, C.elegans as well as human cells."

Dr Fabrizio Alberti & Dr Christophe Corre:

"CRISPR/Cas9 has revolutionised the way researchers do genome engineering across all fields of science, including agriculture, microbiology and medicine. This is because it is a highly specific and programmable molecular tool that can be employed for a variety of genetic engineering applications, such as for the deletion or the silencing of genes, for the production of point-mutations and for the introduction of foreign genes into genomes.

"Our work at the University of Warwick has made use of CRISPR/Cas9-based genome editing to discover new bioactive molecules and understand their biosynthesis. Our research focuses on Streptomyces bacteria, which are known to produce the majority of the antibiotics currently used in the clinic. Several molecular toolkits have been developed to date to edit Streptomyces genomes. By employing one of these CRISPR/Cas9 toolkits, we were able to inactivate a regulatory gene within a selected Streptomyces gene cluster; this triggered the de-repression of the associated biosynthetic genes that led to the overproduction of a previously uncharacterised molecule, which we named scleric acid. ³ Bioactivity studies revealed that scleric acid inhibits the activity of the cancer-associated molecule nicotinamide N-methyltransferase."

8 October 2020

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