This week, the Royal Swedish Academy of Sciences awarded the 2020 Nobel Prize in Chemistry to Emmanuelle Charpentier and Jennifer A. Doudna for the discovery of one of the hottest biotechnology tools out there – CRISPR! This marks the first time that the award has gone to two women, with Dr. Charpentier and Dr. Doudna representing only the sixth and seventh women to win a Nobel Prize in chemistry.
The CRISPR/Cas system, which is based off of a naturally occurring bacterial defense mechanism, was first identified in the 1980’s and 1990’s, but it was not until 2011 that Dr. Charpentier started to understand the details behind this rudimentary immune system. Partnering with Dr. Doudna, the two scientists explored the method that bacteria use to specifically target DNA for cleavage. More importantly, in 2012 the pair proved that it was possible to create a custom piece of RNA to target any desired DNA sequence. This discovery immediately sparked a flurry of research into both the science behind the CRISPR/Cas system, but also the potential uses of the technology.
The key to CRISPR’s success as a biotechnology tool lies in its ability to specifically cut a target sequence of DNA. Researchers can determine the DNA sequence that they would like to target and design a CRISPR guide RNA, or gRNA, to cut only that particular region. The gRNA contains a sequence that is complementary (containing the opposite base-pairs) to the target DNA – this allows the gRNA to specifically bind to that segment of DNA and is why the CRISPR system is so precise. The actual digestion of the DNA is performed by a protein called Cas, for “CRISPR-associated enzymes”, which combines with the gRNA to specifically cut the DNA sequence. Many Cas enzymes have been discovered, and researchers can use customized versions of the protein to achieve double or single-stranded breaks in the target DNA.
One of the most common uses of CRISPR technology is to digest a gene to disrupt its function. Scientists can design a gRNA that targets their specific gene and insert it and a Cas enzyme into a cell. Once cut, DNA repair mechanisms will try to mend the double stranded break, often resulting in small insertions, deletions, or other mutations that disrupt gene function. In this way, researchers can permanently alter the genetic code of an organism. We’ve written before about CRISPR-based therapeutics for Sickle Cell Disease, but it’s hard to undersell how transformative this technology has been for scientists. Clinical trials are underway around the world, and almost every molecular biology lab now uses the technology in their research. Congratulations to Drs. Charpentier and Doudna for this amazing achievement!