What is CRISPR?
We’ve seen the word and heard there was a Noble Prize for it, but what is CRISPR? It’s an ancient and clever mechanism in bacteria. The tiny single-celled organisms evolved the technique to protect themselves from viruses. A microbiologist discovered the mechanism, and genome engineers turned it into a genetic editing tool.
Clustered Regularly Interspaced Short Palindromic Repeats
Who named it? Francis Mojica, a molecular biologist, discovered the short repetitive sequences and gave them the garbely-worded acronym CRISPR. Some of the sequences were clustered together and scattered throughout the genome. Recognized by their palindromic spelling — the same backward and forwards — Mojica suspected the repeats must have important functions. But what exactly? After years of research, in 2005, he published his discovery:
“This is an immune system. This is an adaptive immune system!”
Mojica anticipated his research would spark biotech innovations, and that’s where genome engineers Jennifer Doudna and Emmanuelle Charpentier jumped in. They reprogrammed the CRISPR mechanism in bacteria as a gene-editing tool. Doudna and Charpentier received the 2020 Noble Prize in Chemistry for their breakthrough work.
What does CRISPR look like? The fuzzy image of tiny gray shapes shows thousands of CRISPR molecules through a cryo-electron microscope (middle). The grid of blobs is an attempt to see them as 3-D projections (right). The specs and the blobs don’t tell us much about the molecule, do they? (Find an in-depth explanation about the cryo-electron microscope images here).
That’s why scientists ask graphic artists to show the critical functions in simple diagrams — like Marius Walter’s elegant example below. His diagram and my simplified version of it (on top of this page) direct us to the key elements of the CRISPR Cas9 editing system.
See the green shapes labeled “Target” in the diagram? The guide RNA (gRNA) is programmed to find the Target on a specific sequence of double-stranded DNA (dsDNA) and cut at that precise location (cleavage). For a closer look at the system in action watch, the Jennifer Doudna approved “CRISPR gene-editing systems 3D animation.”
The system works in all living organisms. Researchers can edit any physical location of a gene or a specific sequence on a chromosome. And delete or add a short sequence of new code. When you read about editing, scripting, writing, re-coding, or programming* DNA and RNA, scientists are probably using CRISPR.
CRISPR is more than cool tech. It’s saving lives with treatments for cancer and inherited diseases. It’s an essential tool to combat climate change. Genome engineers are racing to script life for a healthy planet as the crisis accelerates. And genome engineering tools build on the CRISPR system are changing fast, becoming more precise, cheaper, and easier to use.
Key take-away: Stumbling across a curiosity and wondering, what is it for, how does it work — are questions about the fundamental mechanisms of Nature. Focusing on the basics can lead to something marvelous, perhaps even a practical application — voila, CRISPR!
Curious to know what’s next? Don’t wait for the headlines. Read the latest peer-reviewed papers in the scientific journals Science and Nature. Keep up with developments by attending the next CRISPR meeting at CSHL. Follow Eric Green, Director of the National Human Genome Research Institute (NHGRI) on Twitter for updates on their Bold Predictions for genomic research.
*Editing, scripting, writing, re-coding, and programming are sometimes used as interchangeable terms for making changes to genetic sequences.