Developers of CRISPR-Cas9 win Nobel Prize in Chemistry 2020

As with all big discoveries, the discovery of CRISPR-Cas9 as genetic “scissors” was built upon years of previous research. Scientists had been looking into the ability of prokaryotes or single-celled organisms like bacteria and archaea to destroy viral DNA and fight infection within minutes. By 2007, scientists already knew that CRISPR-Cas was the reason bacteria were able to put up this fight against many viruses.

Emmanuelle Charpentier and her team at the Max Planck Unit for the Science of Pathogens, Berlin, Germany, discovered that precise gene-splicing is something that Streptococcus pyogenes bacteria do all the time to overcome viruses. She also discovered that the bacteria do this by using something called tracrRNA—a part of the bacteria’s CRISPR-Cas immune action that cleaves (cuts) viral DNA to fight off viral infections. Charpentier published her findings in 2011.

Charpentier then collaborated with biochemist and RNA expert Jennifer A. Doudna of the University of California, Berkeley, California, to recreate and simplify the “bacteria’s genetic scissors” in a lab. Charpentier and Doudna also showed that these genetic scissors could be used on any DNA at a predetermined site so a new code could take its place—basically, you could cut and paste DNA. By 2012, they had created a gene-editing tool called CRISPR-Cas 9 that was precise and relatively easy to use.

In 2015, Doudna gave a TED Talk in which she explained how the technology works:

• Bacteria have an adaptive immune system called CRISPR. Adaptive immunity (as opposed to innate immunity that one is born with) gets stronger as it fights more pathogens. CRISPR allows bacteria to detect viral DNA.
• Once the CRISPR system is alerted to the viral DNA, it makes an RNA strand that is a replica of the DNA—DNA is made up of two strands that have four types of nucleotides repeated over and over: A, T, C and G. As both RNA and DNA are made up of nucleotides, they can interact with each other. 
• Cas9, a protein associated with CRISPR, scans the viral DNA to find the exact location where the new RNA can fit like a key into a lock. It cuts the viral DNA in this spot and makes room for the new RNA to take its place.
• In short, CRISPR uses a protein called Cas9 to cut and degrade the viral DNA. Doudna and Charpentier figured out that this protein could be used to delete and insert different pieces of DNA at very precise locations into any host, not just bacteria.

CRISPR stands for clustered regularly interspaced short palindromic repeats. CRISPR is an adaptive immune system, so it remembers which viruses have attacked it in the past and can even protect future generations of cells from it. (In the TED Talk, Doudna equated CRISPR to a “genetic vaccination card in cells”). Cas9 is short for CRISPR-associated protein 9.

Genetic diseases are the result of a mutation or glitch in the DNA sequence. A lot of research has already gone into identifying the specific mutations that can cause a number of diseases. Scientists using CRISPR-Cas 9 often use this information to edit a cell taken from the patient.

Next, they use CRISPR Cas9 to introduce a double-stranded break in DNA at the location of the mutation. Normally, in the absence of new genetic information, the cell would automatically repair the DNA without fixing the problem. However, CRISPR Cas9 scientists also introduce new genetic material when they send the edited cell back into the patient’s body. The cell does the work of integrating the new genetic sequence at the site of the DNA break, as part of its natural repair process.

Now every time the body makes a new cell, it shares the entire genome with this new cell. The hope with CRISPR Cas9 is that the new cells will inherit the fixed DNA rather than the faulty one and pass it on to future cells until the problem itself is fixed.

Scientists believe that people with inherited genetic disorders like Down syndrome, cystic fibrosis and thalassemia could benefit from this technology—trials are already underway to test its useful for sickle cell anaemia, beta-thalassemia, multiple sclerosis, cancer and congenital blindness, among other health conditions.

(In February 2020, researchers at the University of Pennsylvania published their findings from a clinical trial in which they put edited T cells in the bodies of three cancer patients—though the CRISPR-Cas9 edited cells were “well-tolerated” and safe with no significant side effects, this specific edit couldn’t stop cancer from progressing in the three patients. This is, of course, a small setback, and more trials are underway to determine how genes may be edited to cure previously incurable diseases.)

The Nobel Prize for Charpentier and Doudna is only the sixth and seventh chemistry Nobel Prize for women scientists since The Royal Swedish Academy of Sciences instituted it in 1908. Before them, the women who won the chemistry prize were Marie Curie (née Sklodowska) in 1911, Irène Joliot-Curie in 1935, Dorothy Crowfoot Hodgkin in 1964, Ada E. Yonath in 2009 and Frances H. Arnold in 2018.