- Kelly Shen ’23, photo from Wikimedia Commons
Last week, the Nobel Prize in chemistry was awarded to Dr. Jennifer Doudna, who is known for pioneering the CRISPR gene editing tool. In this article, we will be going over what CRISPR is and how Doudna made her groundbreaking discovery.
What CRISPR Is and How it Works:
CRISPR is a gene editing tool that enables us to change the DNA in cells. “CRISPR” stands for “clusters of regularly interspaced short palindromic repeats.” “CRISPR” (pronounced “crisper”) is shorthand for “CRISPR-Cas9.” CRISPRs are specialized stretches of DNA. The protein Cas9 is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA. CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea (the domain of single-celled microorganisms). These organisms use CRISPR-derived RNA and various Cas proteins, including Cas9, to foil attacks by viruses and other foreign bodies. They do so by chopping up and destroying the DNA of a foreign invader. When these components are transferred into other, more complex, organisms, it allows for the manipulation of genes, or “editing.”
How it got discovered:
UC Berkeley professor, Jill Banfield, first encountered CRISPR while studying bacteria living in extreme environments. The system intrigued Doudna, who wondered how an unusual repeating sequence of DNA in the bacterial genome enabled bacteria to mount a successful defense against viral infections. What they and other researchers realized is that when viruses invade bacteria, the bacteria cut up the viral DNA and place these pieces in their genome, like “most wanted posters.” If similar viruses invade again, roving enzymes with RNA copies of these bits of viral DNA examine the virus and, if the RNA and DNA match, cut the DNA and kill the virus.
Emanuelle Charpentier, who also won the chemistry Nobel Prize for her work in CRISPR, focused on the Type 2 system (CRISPR-Cas9) and described an unusual RNA not found in other CRISPR systems — the tracrRNA. What she found is that it works together with the Cas9 protein to help generate the RNA copies of the “most wanted posters.” She and Doudna then considered how the Cas9 protein might also be involved in the final step of CRISPR immunity: surveilling the cell and cutting up invading DNA. The two began their collaboration that year after meeting at a scientific conference in Puerto Rico and would eventually create the amazing technology that shook the science world.
Doudna on winning the Nobel Prize:
“This great honor recognizes the history of CRISPR and the collaborative story of harnessing it into a profoundly powerful engineering technology that gives new hope and possibility to our society,” said Doudna. “What started as a curiosity‐driven, fundamental discovery project has now become the breakthrough strategy used by countless researchers working to help improve the human condition. I encourage continued support of fundamental science as well as public discourse about the ethical uses and responsible regulation of CRISPR technology.”
“Many women think that, no matter what they do, their work will never be recognized the way it would be if they were a man,” said Doudna, who was awakened from a sound sleep by a reporter at 2:53 a.m., learning for the first time that she’d won a Nobel. “And I think [this prize] refutes that. It makes a strong statement that women can do science, women can do chemistry, and that great science is recognized and honored. That means a lot to me personally, because I know that, when I was growing up, I couldn’t, in a million years, have ever imagined this moment.”