It sounds like science fiction – and it was until 2012 that the ability to cheaply and easily edit DNA strings was exactly that. But it turns out, CRISPR / Cas9 gene editing is a completely natural function, in which the bacterium catalogs its interactions with the virus by taking a piece of the virus’s genetic material and saving it later. this.
Now, two women have won the Nobel Prize in Chemistry in 2020 “for developing a method to edit the genome”. Emmanuelle Charpentier and Jennifer Doudna leveraged CRISPR into a genetic scissors and showed how responsive they were by demonstrating that they could modify any DNA sequence in this way. Since Emmanuelle and Jennifer published their 2012 article in CRISPR / Cas9, researchers have used these genetic scissors to create drought-tolerant plants and seek gene-based cancer therapies. new. Researchers are also hoping to use CRISPR / Cas9 to cure genetic diseases like Huntington and sickle cell anemia.
The discovery begins with Emmanuelle Charpentier’s investigation of about Streptococcus pyogenes bacteria. She is trying to understand how its genes are regulated and hopes to create an antibiotic. When she collaborated with Jennifer Doudna, they found a scientific breakthrough.
Emmanuelle Charpentier fights meat-eating bacteria
Emmanuelle Charpentier was born on December 11, 1968 in Juvisy-sur-Orge, France. She studied biochemistry, microbiology and genetics at Pierre and Marie Curie Universities, now known as the Sorbonne University. She then received a PhD in research from the Pasteur Institute and worked as a university teaching assistant and research scientist. Dr. Charpentier is currently the director at the Max Planck Institute for Infectious Biology in Berlin, and in 2018, she founded an independent research unit.
After completing her PhD, Dr. Charpentier spent a few years working in the United States before coming to work at the University of Vienna, where she started a research group. Her focus remains on bacteria Streptococcus pyogenes, which causes millions of people to develop infections such as tonsillitis and impetigo each year. It also caused sepsis, officially turning it into a carnivorous bacteria.
In 2009, Dr. Charpentier moved to northern Sweden to accept a research opportunity. She continues to work S. pyogenes and mapping the small RNAs found within. Along the way, Dr. Charpentier discovered a small RNA molecule whose genetic code is actually close to the CRISPR sequence in its genome.
Although she has never worked with CRISPR before, Dr. Charpentier asked her team to map out the CRISPR system in S. pyogenes bacteria. The system was shown to need only a single Cas protein to cleave the viral DNA, but Dr. Charpentier discovered that a small RNA molecule, now named the switch-activated crispr RNA or tracrRNA was needed. for the maturation of the long RNA generated in the CRISPR process. At the time, Dr. Charpentier was very excited about CRISPR and wanted to collaborate with a biochemist to promote research. Her number one choice is Jennifer Doudna.
Jennifer Doudna ran RNA interference
Jennifer A. Doudna was born on February 19, 1964 in Washington, DC, but raised in Hilo, Hawaii. She earned her bachelor’s degree from Pomona College in 1985, and her doctorate from Harvard Medical School in 1989. Dr. Doudna is currently professor of chemistry and molecular and cellular biology at UC Berkley as well as assistant professor. lectures in molecular and cellular pharmacology at UC San Francisco.
Before starting her career, Dr. Doudna studied RNA enzymes in the hopes of discovering their structure and biological function. Two decades later, her lab is still focused on RNA, where they are working to understand RNA-related biological processes by combining the use of CRISPR, microRNA, and RNA interference.
The last process, RNA interference, is the process by which RNA processes gene regulation. It is also known as silent RNA. In RNA interference, the production of a gene’s protein is turned off by a small interfering RNA – a tiny RNA molecule that hunts for any messenger RNA that exactly matches it and sends them flying.
In 2006, Dr. Doudna got a call from a fellow microbiologist telling her about a new discovery called CRISPR. The colleague said that no one knew much about it, but they suspected it acted like RNA interference. Researchers compared several very different bacteria and found that they all share some of the same repeating DNA sequences. The repeating sequences themselves are called CRISPR – short, regularly spaced, palindromic repeating sequences. In the sequences are shorter and unique, non-repeating sequences that match the genes of different viruses. So the hypothesis is that bacteria take a souvenir from every virus they survive, like collecting teeth on a necklace.
Dr. Doudna also knows that researchers have discovered special genes that they call CRISPR binding, or Cas. She led her team to follow the Cas proteins, wondering if their goal was to cut the DNA chains.
Pair to hunt for scissors
In the spring of 2011, Dr. Charpentier was asked to speak at a conference in Puerto Rico to discuss her findings on tracrRNA. She decided to use the opportunity to introduce herself to Dr. Doudna.
The two met by chance at a coffee shop on the second day of the conference, introduced by a colleague of Dr. Doudna. The next day, while walking through the old streets of the capital, they decided to collaborate and study the function of the Cas9 protein in S. pyogenes. They suspect that longer CRISPR-RNA is what determines the viral DNA and that the Cas9 protein performs the cutting.
Over the next few months, the two groups performed many DNA separation experiments, but nothing happened. Finally, they added tracrRNA to the pot, and here, the DNA molecule is cut in half.
Not stopping there, they worked to simplify the scissors by combining tracrRNA and CRISPR-RNA into a single molecule, now known as the guide RNA. They went on to accurately cleave one gene in five different places before presenting their 2012 paper in CRISPR / Cas9.
The future of gene editing
CRISPR is an interesting field because there are so many different ways it can be used in both the animal and plant kingdom. Dr. Doudna discussed some of those methods in this interview with Future Human shortly after winning the Nobel Prize. Her company Mammoth Biosciences is working on a CRISPR-based rapid test for COVID-19 and hopes to have a test as simple as a home pregnancy test. She has another CRISPR company that focuses on neurodegenerative diseases like Alzheimer’s and Parkinson’s.
We’re thrilled to see all the places where CRISPR / Cas9 gene editing takes us. Congratulations, Dr. Charpentier and Doudna!