The story behind CRISPR Cas9 - a string of discoveries

"The science of CRISPR has potential to challenge the creations of God"
The-story-behind-CRISPR-Cas9-a-string-of-discoveries (Unsplash)
The-story-behind-CRISPR-Cas9-a-string-of-discoveries (Unsplash)

In 1987, a japanese student Yoshizumi Ishino discovered a repeating section of DNA in bacteria. He was sequencing a gene iap (isozyme of alkaline phosphatase) responsible for isozyme conversion of alkaline phosphatase in E.Coli. This repeated sequence was something that had never been seen before.

The-story-behind-CRISPR-Cas9-a-string-of-discoveries (Unsplash)
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In the paper, Ishino noted that the gene seemed to contain repeating sequences (which were palindromic in nature) of 29 base pairs, separated by unique sections of DNA. But he was not able to find out the purpose of those sequences. His paper ends with the immortal words “ Biological importance of these sequences is not known, and homologous sequences to these have not been found elsewhere in prokaryotes”.

Some years later in 1990, Francisco Mojica, a student at the University of Alicante in Spain, was studying archaea - single-celled organisms that are very similar to bacteria. He noticed that the same palindromic sequences were present in both archaea and bacteria. He named the sequences CRISPR. But how did they come up with the name CRISPR?

The-story-behind-CRISPR-Cas9-a-string-of-discoveries (Unsplash)
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On 23 October 2017, Kevin Davies, (founding Executive Editor of The CRISPR Journal) during an interview with Francisco Mojica asked the same question.

"Davies : How or when did the name change to CRISPR?

Mojica: In 2000, we found a new family of repeats. The first name given was (short regularly spaced repeats) SRSR. In 2001, a group in the Netherlands that was working on Mycobacterium tuberculosis sent me a mail. They were calling them DR (Direct Repeats). They found four genes related to CRISPR and wanted to give a different name to these CRISPR-associated (Cas) genes but didn't like SRSR. We were in search of a name that is easy to pronounce. I suggested the name CRISPR. "

The-story-behind-CRISPR-Cas9-a-string-of-discoveries (Unsplash)
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They found this name, CRISPR, unique as well as interesting and accepted the same. Using a bioinformatics tool called blast he found out that spacers present in CRISPR were matching the other DNA sequence belonging to viruses.

Why would viral DNA end up inside bacteria? Mojica hypothesized that these spacers encoded instructions for an immune system to protect bacteria against these viruses.

Using a bioinformatics tool called blast he found out that spacers present in CRISPR were matching the other DNA sequence belonging to viruses. Why would viral DNA end up inside bacteria? Mojica hypothesized that these spacers encoded instructions for an immune system to protect bacteria against these viruses (CDC PHIL)
Using a bioinformatics tool called blast he found out that spacers present in CRISPR were matching the other DNA sequence belonging to viruses. Why would viral DNA end up inside bacteria? Mojica hypothesized that these spacers encoded instructions for an immune system to protect bacteria against these viruses (CDC PHIL)

In 2008 John Van Der Oost (Dutch microbiologist) found out how the CRISPR Cas9 system interfered with bacteriophage. He demonstrated that phage derived E. Coli spacer sequences are transcribed into small RNAs called Crispr RNAs, that guide Cas protein to the target DNA. Some years later Emmanuelle Charpentier established a full mechanism of CRISPR. She accidentally discovered the last essential component of the CRISPR system called tracrRNA.

The-story-behind-CRISPR-Cas9-a-string-of-discoveries (Unsplash)
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Lithuanian molecular biologist called Virginijus Siksnys successfully moved the CRISPR from in-vivo to in-vitro, while Emmanuelle Charpentier & Jennifer Doudna artificially created a single guide RNA or sgRNA which substituted the function of tracrRNA & crRNA. After this discovery, several scientists worked on gene editing.

Feng Zhang bioengineer professor (Broad Institute at MIT) and George Church geneticist professor (Harvard), in the year 2012, found that we can also use the CRISPR Cas9 system to edit human DNA. With this technology one day we might be able to design the next generation to be free from diseases (Unsplash)
Feng Zhang bioengineer professor (Broad Institute at MIT) and George Church geneticist professor (Harvard), in the year 2012, found that we can also use the CRISPR Cas9 system to edit human DNA. With this technology one day we might be able to design the next generation to be free from diseases (Unsplash)

Feng Zhang, bioengineer professor (Broad Institute at MIT) and George Church, geneticist professor (Harvard), in the year 2012, found that we can also use the CRISPR Cas9 system to edit human DNA. With this technology, one day we might be able to make the next generation free from diseases.

"The science of CRISPR has potential to challenge the creations of God"

Yogesh Patil, Tutor - Department of biotechnology, MGM School of Biomedical Sciences

For this great discovery, Emmanuelle Charpentier and Jennifer Doudna have been awarded the 2020 Nobel Prize in Chemistry. As we know many scientists have hugely contributed to the discovery of CRISPR.

Whom do you think owns CRISPR? Let the debate begin!

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