Arguably, Jennifer Doudna’s most famous piece is her article that was published in Science magazine on June 28th, 2012 that talked about the groundbreaking discoveries her laboratory had made about CRISPR gene editing and the Cas9 enzyme. The paper was titled “A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity”. The paper discusses three major discoveries in quick succession. To understand these discoveries there are three important factors that need to be defined. The Cas9 enzyme is what allows the bacteria to cut the DNA but it cannot work without binding to crRNA, which is what guides it to the DNA. What Emmanuelle Charpentier had discovered was that another RNA molecule was required for the process to work, tracrRNA. Without tracrRNA, the crRNA would not be able to bind to the Cas9 enzyme. When this was brought to Doudna’s lab work on CRISPR began to accelerate and Doudna and Charpentier began to work together more closely. The first discovery highlighted in the article is the importance of tracrRNA to the process of CRISPR. After working together Doudna and her lab together with Charpentier were able to deduce the exact mechanisms of the CRISPR-Cas9 complex. “The crRNA contained a twenty-letter sequence that acted as a set of coordinates to guide the complex to a piece of DNA with a similar sequence. The tracrRNA, which had helped create this crRNA, now had the additional role of acting like a scaffold that held the other components in just the right place when they glommed onto the target DNA. Then the Cas9 enzyme began slicing away.” Most fascinatingly, the crRNA could be replaced to change the DNA sequence that was cut. This opened the doors to the possibilities of programmable gene editing with CRISPR. However, Doudna was not done yet. Their next goal was to find a way of simplifying the CRISPR process so it could become a cheaper and easier method than other gene-editing tools at the time. First, they found that they could truncate some off of each RNA molecule (crRNA and tracrRNA) without affecting the rest of the process. This led Doudna and Martin Jinek to discuss the possibility of combining the two molecules together, which they were able to eventually do. After only three weeks of work, Martin Jinek and Krzysztof Chylinski were able to create a single-guide RNA (sgRNA). This was the third and final discovery mentioned in the paper. These CRISPR discoveries led to major breakthroughs in science and have pushed the limits on what many believed was possible with gene editing. Doudna made some of the largest contributions to understanding and simplifying the CRISPR process, however, CRISPR could not be used in many of the ways we picture today without the contributions of Feng Zhang. Zhang, who works at MIT, discovered how to use the CRISPR process within eukaryotic cells (animal/human cells). It is also worth noting the ethical debate that these discoveries have raised. There are many possibilities that are unlocked with this tool, but the discussion of what it should and should not be used for is ongoing, and the reveal by He Jiankiu on November 25, 2018, that he had genetically modified twins in the embryo using CRISPR greatly accelerated it. CRISPR is a fascinating technology with a multitude of beneficial applications, but it should not be discussed without mentioning the ethical implications and without looking at the massive group of people from across the world that each contributed in large and small ways towards the understanding we have now.
4 Comments
Nathan Rabinovitch
1/11/2022 08:09:15 am
The technical information presented in the paper that made it famous is described very well in this blog post. The diagram shown definitely helps. This article already has more than enough content, but it you're ever looking for more you may want to look into the copyright debate over CRISPR between the universities backing a few of the main scientists.
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Loren Sinclair
1/11/2022 10:51:36 am
Nice!! You explain it in such detail, nice work! It's really interesting stuff too!
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Mia Enriquez
1/11/2022 01:16:52 pm
What a lovely, accessible summary. Scientific papers publishing such revolutionary discoveries always interest me, as the nature of science writing means that they are often almost comically underwhelming or aware of their own significance and struggling to maintain an appropriate scope and tone. Good topic good post!
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Natalie Nardino
1/11/2022 06:25:22 pm
The diagram was really helpful in understanding the concept of the paper! The combination of opinion, summery, and background was done well. It was enjoyable to read.
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AuthorMy name is Nathan Eberhart. I have a curious mind and am a creative thinker with an interest in biomedical engineering and medical devices. Archives
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