Exquisite Science
Christopher Dowdy, PhD

As a Xennial, the CRISPR Nobel is Exciting

The game-changing tool has changed a lot of things, including the field of model creation

Exciting news that the 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmanuelle Charpentier for their discovery of CRISPR editing!

As we have written and podcasted over the past few years, CRISPR gene editing has accelerated research throughout the biomedical community. Many processes that took months or years have been condensed to weeks or months, and core features of CRISPR have been leveraged as wide ranging tools.

For context of how I view the rise of CRISPR, I’m a Xennial. We are a micro-generation of Americans, born in the late 1970s – early 1980s who grew up with the internet. My parents worked in telecommunications and software development, so we were among the first to have computers in the home at the time. I remember the sound of a dial up modem, and eagerly waiting minutes for a text only web site to load. In a few short decades, that technology exploded and now influences every aspect of our lives. People all over the world walk around with phones in their pockets that have 100,000 times the processing power Apollo 11 used to land on the moon, and 7 million times the storage. CRISPR is analogous to going from dial up modems to 5G smartphones in only 8 years.

Genetic engineering has existed for decades. Homologous recombination in mice received the Nobel Prize in 2007, for expanding on work in bacteria which earned the Nobel Prize in 1958. The next step in gene editing came from the understanding of how cells repair DNA damage, and that if DNA was cut at a precise location, researchers could then look for the exact repair they needed. Conceptually this approach of directed DNA repair will work with anything that breaks DNA in a defined way. Unfortunately, the early tools (like Zinc Fingers and TALENS) had to be designed specifically for each target, making them complex to design and subsequently slow to catch on.

The game-changing aspect of CRISPR is that the cutting mechanism itself is the same for any target in the genome. Specificity is through small RNAs. When CRISPR landed, the biomedical community was getting quite good at designing and synthesizing RNA, since the Nobel Prize in 2006 for RNA interference. Suddenly, directed DNA damage and repair became much easier.

CRISPR technology was quickly leveraged for making animal models. The Knockout Mouse Project (KOMP), whose objective is to systematically disrupt every gene in the mouse to further basic research, began with a homologous recombination approach and switched over to CRISPR assisted approach for challenging genes. Now CRISPR is the default approach for most groups generating new animal models.

Aside from direct cutting, CRISPR systems have been adapted with a modified nuclease that cannot cut DNA, and instead fused with a domain to activates or inhibits the target. Coupled with the ease of targeting by guide RNAs, high throughput screening for functional genomics is being done at scale. As with many key technologies, the contributions to the field will likely extend far beyond the original vision.

We are happy to join the chorus of voices congratulating Drs. Douda and Charpentier on this award!