The Molecular Scissors that Improve Society

CRISPR is a powerful tool that enables scientists to precisely edit DNA, revolutionizing medicine, agriculture, and biotechnology.

A group of people standing in front of a machine.
Image courtesy of Roy Kaltschmidt, Berkeley Lab
Berkeley Lab scientists Jennifer Doudna, Blake Wiedenheft, Eva Nogales, and Gabriel Lander around a cryo-electron microscopy system. The team used microscopy and 3D image reconstruction to build an atomic-scale map of a CRISPR-related molecular complex.

No one would confuse a bacterium, a plant, or a human, but they’re all based on the same fundamental building block: DNA. By developing a pair of genetic scissors that can work in all of them – and in fact, in any organism – researchers developed a powerful tool for studying life and solving some of society’s biggest challenges.

CRISPR-Cas systems are molecular machines derived from bacteria that allow scientists to change or remove genes quickly, with a precision only dreamed of just a few years ago. With these tools, scientists can more easily study how genes work, engineer an improved crop, or biomanufacture essential compounds. Researchers are also exploring CRISPR-Cas gene editing in medicine to cure previously untreatable genetic diseases, develop cancer treatments, and slow the spread of viral illnesses. This new era of genomic science began with fundamental research by Lawrence Berkeley National Laboratory (Berkeley Lab) scientist Jennifer Doudna.

“One of the reasons that I love being at the University of California, Berkeley and working with Berkeley Lab is that we scientists have the opportunity to do fundamental science that ultimately will impact people's health and our lived experience as humans,” said Doudna, who shared the 2020 Nobel Prize in Chemistry with Emanuelle Charpentier for the development of the CRISPR-Cas9 system. “CRISPR is a wonderful example of science that started with the most basic curiosity-driven questions and has now progressed to the point where it's a powerful tool that's integrated into most biological research around the world.”

“We use CRISPR nearly every day in my lab to engineer bacteria and yeast to produce natural and new-to-nature products,” said Jay Keasling, CEO of the Joint BioEnergy Institute. Keasling’s group uses microbes to produce chemicals and fuels that are conventionally made from petroleum as well as drugs and natural products that would otherwise be impossible to produce at large scale, such as antimalarials and chemotherapies. “Just like polymerase chain reaction (PCR), I can’t imagine doing research without it. It has been a game-changer.”

Doudna was investigating the many functions of RNA, the single-stranded form of genetic material, when she joined UC Berkeley and Berkeley Lab in 2002. While working at both institutions, she met microbiologist and earth scientist Jillian Banfield, who was studying a unique immune adaptation she’d found in bacteria sampled from the environment. These bacteria had many copies of viral DNA sequence fragments embedded within their own genome, and this somehow allowed them to defend against infections.

Two people sitting in front of a computer.
Image courtesy of Roy Kaltschmidt, Berkeley Lab
Jennifer Doudna and James Nunez, who earned his PhD in Dounda's Lab. He is now an Assistant Professor in the Department of Molecular & Cell Biology at UC Berkeley and a Hanna Gray Fellow of the Howard Hughes Medical Institute.

Banfield and Doudna, alongside others in the research community, soon discovered that the DNA sequences – called CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats – are part of a threat identification system. When viruses with DNA matching one of the embedded sequences try to attack the bacteria, circulating RNA will find the sequence and usher over enzymes called Cas to cut the viral DNA, inactivating the virus. Doudna’s early studies on CRISPR were funded by a research grant from the Department of Energy.

Meanwhile, her soon-to-be research partner, Charpentier, was studying CRISPR-Cas9, a particularly interesting version of this system that uses two RNA guide molecules to precisely choreograph the Cas9 cutting enzyme into place on flagged viral genetic material. The two met at a conference in 2011 and decided to further investigate the system together.

Using their insights on how the system worked, they developed a method for engineering a single guide RNA molecule that combines the functions of the two natural Cas9 guides. Then they demonstrated that their streamlined system could target and cut any DNA sequence in any organism. In the paper describing this seminal work, published in Science in 2012, Doudna and Charpentier proposed that their modified CRISPR-Cas9 system had potential far beyond a cellular defense mechanism. They stated that it could perform targeted edits, gene deletions, and insertions faster and easier than any existing method – a promise that held true.

“The larger impact of CRISPR to the general public is twofold. One is in healthcare, because it's a technology that is really accelerating the pace at which we can understand our own genetics and then intervene to make changes to genes that are disease causing,” said Doudna, noting that the first CRISPR therapeutic, which shows promise to cure sickle-cell anemia, is expected to be approved by the FDA next year. “The other area of very significant impact for the public with CRISPR is in agriculture and climate change.”

She and her collaborators are using CRISPR to make changes in plants that give them resistance to drought and disease. They are also making modifications to give microbiomes in the soil and water the ability to both reduce the emissions of greenhouse gasses and also to help support commercial agriculture as the environment changes.

This article was created in partnership with Berkeley Lab, learn more about their work.

Read more stories in the Basic2Breakthrough series.