The gene-editing method CRISPR-Cas9

CRISPR was first discovered by Ishino and coworkers at Osaka University in Japan while cloning a peculiar gene-repeat (Ishino et al. 5429-30). Nearly two decades later, a group of researchers at the food ingredient producer Danisco in Madison, United States, discovered that these CRISPR repetitions in bacteria offered defense against viral infection. (Barrangou et al. 1709-11). The prospect of using CRISPR-Cas9 as a tool for gene-specific manipulation was made possible by Marraffini and Sontheimer's 2008 discovery that it targets DNA rather than RNA (as was originally thought). After that, a group of researchers from the University of California, Berkeley, clarified how CRISPR-Cas9 works. (Jinek et al. 816-18). Two leading scientists of this study - Jennifer Doudna and Emmanuelle Charpentier – would later emerge as the major contenders for the patent ownership of this path-breaking technology. A year later, in 2013, scientists at Whitehead Institute for Biomedical Research, Massachusetts used this technology to successfully target and edit genes in mice. Soon thereafter, researchers at the University of California, San Francisco applied CRISPR-Cas9 to correct thalassemia in human (Xie et al. 1526-30). The exhaustive review article published in Cell provides further insight into the topic (Hsu et al. 1262-1276).



Author’s Analysis o Author’s Evaluation o Author’s Rationale (line of reasoning) o Author’s Recommendations (if any)



The cited articles are all published from the laboratories of key scientific players working on the CRISPR-Cas9 technology worldwide. The chronology of events demonstrates the collective effort of several researchers over the years that led to the current status of this gene-editing technology. The advances made over the years, from the serendipitous discovery of the gene sequence in bacteria to its application for genetic manipulation in humans. CRISPR-Cas9 continues to be a highly researched topic all over the world, and as indicated by the publications, the field is emerging with newer developments rapidly. While there is an existing consensus on the potential of this technique for wide range of applications from curing cancer to developing newer hybrids, considerable research needs to be undertaken for developing practical applications of this tool.



Works Cited



Barrangou, Rodolphe, et al. "CRISPR provides acquired resistance against viruses in



prokaryotes." Science 315.5819 (2007): 1709-1712.



Hsu, Patrick D., Eric S. Lander, and Feng Zhang. "Development and applications of CRISPR



Cas9 for genome engineering." Cell 157.6 (2014): 1262-1278.



Ishino, Yoshizumi, et al. "Nucleotide sequence of the iap gene, responsible for alkaline



phosphatase isozyme conversion in Escherichia coli, and identification of the gene product." Journal of bacteriology 169.12 (1987): 5429-5433.



Jinek, Martin, et al. "A programmable dual-RNA–guided DNA endonuclease in adaptive



bacterial immunity." Science 337.6096 (2012): 816-821.



Wang, Haoyi, et al. "One-step generation of mice carrying mutations in multiple genes by



CRISPR/Cas-mediated genome engineering." Cell 153.4 (2013): 910-918.



Xie, Fei, et al. "Seamless gene correction of β-thalassemia mutations in patient-specific iPSCs



using CRISPR/Cas9 and piggyBac." Genome research 24.9 (2014): 1526-1533.

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