How Cas proteins kill harmful genes and help create new DNA editing tools
Immunity to diseases isn't the preserve of people and other large organisms — bacteria have it, too. Bacteria fight their enemies, bacteriophages (viruses that infecting bacterial cells), using the CRISPR-Cas molecular complex, the key component of which is the Cas effector protein.
When a virus infects a bacterium, it injects its genomic DNA into it. The Cas protein sees what has happened and cuts the enemy's genes. A paragraph of the viral DNA is then integrated into the bacterial genome. It becomes a "spacer" — a part of the CRISPR system. The spacer is something like a visiting card taken from the virus, by which the bacterium will quickly recognize and destroy its enemy if it tries to attack again.
The bacterial immune system has been intensively studied since the end of the 1980s, and in 2013 it was decided to use CRISPR-Cas systems to cut DNA in eukaryotic cells (including human eukaryotic cells). The attempt was successful.
The next step was to consider how CRISPR-Cas could be used in the treatment of hereditary diseases. Bioinformaticians were looking for Cas effectors with various properties, bioengineers were modifying discovered proteins to build up more and more DNA editing tools on their basis.
Skoltech student Iana Fedorova was one of those working to create a tool, which could "turn off" several genes at once. She was working in the team of Feng Zhang, the scientist who was one of the first to test CRISPR systems in eukaryotic cells. An article describing the team's findings was published in Nature Biotechnology journal in 2017*.
Our comic strip draws on that article to tell the story of CRISPR-Cas technologies. _________________________ Bernd Zetsche, Matthias Meidenreich, Prarthana Mohanraju, lana Fedorova et al. "Multiplex gene editing by CRISPR-Cpf1 using a single crRNA array". Nature Biotechnology, 2017, Vol. 35, pp. 31-34. DOI:10.1038/nbt.3737.
Drawn by
Nikolay Ogarkov
Original idea and words by
Alyona Lesnyak
main characters
name: IANA FEDOROVA status: researcher
Biophysicist, graduate of Peter the Great Polytechnic University (St. Petersburg); Research Scientist at the Molecular Microbiology Laboratory at Peter the Great Polytechnic University and student at the Center for Life Sciences of the Skolkovo Institute of Science and Technology (Skoltech)
name: KONSTANTIN SEVERINOV status: supervisor
Graduate of the Biology Faculty at Moscow State University, PhD in Biology, Director of the Center for Life Sciences at Skoltech, Professor at Rutgers University (USA)
name: Cas12a aka CPF1 status: Object of research
Effector protein, part of one of the genome-editing CRISPR system types. Discovered by bioinformaticians in 2015 in the bacterium Francisella novicida
name: Cas9, or rather SpCas9 status: Celebrity
The first, best known and most respected effector protein, discovered at the start of the 2000s in the bacterium Streptococcus pyogenes
name: Laboratory mouse C57BL/6 status: Model organism
С57BL/6 is a breed of brown and gray (sometimes almost black) laboratory mice. One of the organisms most frequently used in research