CRISPR Discovery

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The page below is a sample from the LabCE course CRISPR: From Nature to Bench and Bedside. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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CRISPR Discovery

While conducting a biochemical study using E. coli cells at Osaka University in Japan in 1987, Dr. Yoshizumi Ishino observed a unique pattern in DNA sequence that repeats multiple times and with a different spacer content between the DNA repeats.1,2 Due to the rudimentary nature of DNA sequencing technologies back then, follow-up studies were a long process. In 1993, the same unique repeat DNA sequences were noticed in archaea.3 It was not until more than two decades later that more in-depth CRISPR characterization was carried out as more sophisticated sequencing apparatus became available. It was finally confirmed that the unusual repeat-spacer-repeat-spacer-repeat pattern is a brilliant bacterial immune defense system that helps bacteria recognize and combat invading viruses that preferentially target and infect bacteria.4
Today, this system is known as “clustered regularly interspaced palindromic repeats” using the acronym CRISPR.
1. Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., & Nakata, A. (1987). 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), 5429–5433. https://doi.org/10.1128/jb.169.12.5429-5433.1987
2. Ishino, Y., Krupovic, M., & Forterre, P. (2018). History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology. Journal of bacteriology, 200(7), e00580-17. https://doi.org/10.1128/JB.00580-17
3. Mojica, F. J., Juez, G., & Rodríguez-Valera, F. (1993). Transcription at different salinities of Haloferax mediterranei sequences adjacent to partially modified PstI sites. Molecular microbiology, 9(3), 613–621. https://doi.org/10.1111/j.1365-2958.1993.tb01721.x
4. Gostimskaya I. (2022). CRISPR-Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing. Biochemistry. Biokhimiia, 87(8), 777–788. https://doi.org/10.1134/S0006297922080090