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How CRISPR works

The science behind the revolutionary discovery, and its tremendous potential as a lifesaver

The CRISPR-Cas9 Technology Developed by Doudna and Charpentier

In June 2012, University of California, Berkeley professor and Howard Hughes Medical Institute investigator Jennifer Doudna and Umea University professor Emmanuelle Charpentier (now at the Max Planck Institute for Infection Biology) and their research team, which included Martin Jinek from UC and Krzysztof Chylinski from the University of Vienna, published an article in the journal Science that first revealed what has been described as the scientific breakthrough of the century. This international team of researchers determined how a bacterial immune system known as CRISPR-Cas9 is able to cut DNA, and then engineered CRISPR-Cas9 to be used as a powerful gene editing technology.

To understand this powerful new technology, think of the CRISPR-Cas9 system as special scissors that cut DNA “threads.” In nature, bacteria use these scissors to cut the DNA threads of invading viruses. The Doudna/Charpentier team figured out how to engineer and use these scissors to cut any DNA thread of their choosing, thereby allowing the system to be used to make repairs or modifications to the intricate, multicolored tapestry that is the human genome.

Additionally, the natural CRISPR-Cas9 system has three separate parts – the scissors portion, which actually cuts the DNA thread, and a two-piece “homing beacon” portion that directs the scissors to the DNA thread. The two pieces of the homing beacon must find each other and come together before the natural CRISPR-Cas9 system can home in on and cut a targeted thread. The Doudna/Charpentier team devised a way to make a one-piece homing beacon, thus simplifying the system and vastly increasing the ease of use of this technology.

The Doudna/Charpentier group’s Science publication immediately ushered in a new and revolutionary era of gene editing. Within six months of the Doudna/Charpentier team’s Science publication describing the engineering and use of the CRISPR-Cas9 system, many research groups successfully applied the CRISPR-Cas9 technology as originally described in that landmark publication, further verifying how readily the Doudna/Charpentier team’s engineered CRISPR-Cas9 system can be used for gene editing in any cell type.

Since publication of the Doudna/Charpentier team’s seminal paper, CRISPR-Cas9 gene editing has transformed biological research across the globe. CRISPR-Cas9 allows scientists to permanently edit the genetic information of any organism – including human cells – with unprecedented ease, accuracy and efficiency. CRISPR-Cas9’s power and versatility has opened up new and wide-ranging uses across biology, including medicine and agriculture. The foundational research of the Doudna/Charpentier research team enabled subsequent work by many laboratories throughout the world that used CRISPR-Cas9 to treat and cure disease in animal models and to create pathways to sustainable biofuels, to more robust crops and to countless other applications that will continue to dramatically advance human health and well-being (for example, therapies for sickle cell disease).

The University of California has a rich history of scientific discovery and development. Our researchers have introduced many of the most significant technologies that have bettered our world and vastly improved the lives of its people. The ongoing work of Doudna and her team is another example of the university’s commitment to pursuing basic and applied research that is in the public interest, which is consistent with UC’s standing as the world’s leading public research university system.

As part of that focus on, and commitment to, the greater good, the University of California, along with the University of Vienna, has reserved the right to allow educational and other nonprofit institutions to use the CRISPR-Cas9 related intellectual property for educational and research purposes. 

How was CRISPR-Cas9 gene editing developed?

The invention of CRISPR-Cas9 gene editing technology was the result of basic research science at its best. More than 10 years ago, Jillian Banfield, UC Berkeley professor of earth and planetary sciences and of environmental science, policy and management, asked Doudna to analyze a genetic peculiarity of bacteria known generally as CRISPR. At that time, CRISPR’s function in bacterial cells was only beginning to be understood. After several years of research by Doudna and her team into various proteins that make up bacterial CRISPR systems, Doudna began collaborating with Charpentier and her team, who had also been researching CRISPR systems, including the identification of tracrRNA.

Their research teams collaborated on studies to determine how the CRISPR-Cas9 system acts like a pair of molecular scissors to cleave the DNA of invading viruses. Through their scientific collaboration, the Doudna/Charpentier research team determined exactly what components were responsible for this DNA cleavage and the team engineered those components to modify target DNA outside of bacterial cells. The studies included making various modifications to the natural components of the system, and even included studies where two separate RNA components from the natural system were combined into a single molecule, thereby simplifying the system and making it easier to employ. This work demonstrated that engineered CRISPR-Cas9 can be used for gene editing. The Doudna/Charpentier research team’s seminal 2012 publication of these results in Science is widely seen as the event that launched a new era of progress in genome editing.

What are the applications for CRISPR-Cas9?

With its vast potential for drug discovery and development, human applications are of particular interest to CRISPR-Cas9 researchers. On a new front in the battle against cancer, scientists are already working to use CRISPR-Cas9 as a means to edit a patient’s T-cells (immune cells) so that they have the capability to target particular types of tumors. Within the next 10 years it is likely that we will see CRISPR-Cas9-based therapies for blood disorders such as sickle cell disease, as well as other genetic diseases. For non-human applications, researchers are applying the CRISPR-Cas9 technology to engineer pest and disease-resistant crops and protect trees from bark beetles, as well as exploring the technology’s ability to control mosquito populations and reduce their ability to spread Zika virus and malaria.