Gene-editing technology is arguably the fastest developing branch of science in the 21st century. The invention of the CRISPR-Cas9 method began a revolution in gene-altering because it’s both cheaper and more efficient than previous techniques. The founders won the Nobel Prize in Chemistry 2020; however, there’s much controversy regarding ethical issues of genetic manipulation.

CRISPR-Cas In Nature

DNA Protection in Prokaryotes

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a family of DNA systems in bacteria and archaea in the natural world. It has a crucial part in the organisms’ immune system. The mechanism is quite simple. The CRISPR DNA fragments come from the genome (an organism’s complete set of genetic instructions. Each genome contains all of the information needed to build that organism and allow it to grow and develop) of a virus that infected the bacteria- bacteriophage. The cell uses them to identify and destroy the bacteriophage if it tries to infect the organism again. Moreover, bacteria can transfer genes between each other so that cells can pass information about the virus from one to another.

Cas9 Enzyme

The Cas9 is an enzyme that uses the CRISPR information as a wanted notice. It uses the sequences’ data to find DNA fragments that ‘fit’ to the CRISPR sequence. This means that CRISPR has a sequence that forms pairs with the virus’s DNA. When two sequences ‘match’, we call them complementary.

Visualization of the CRISPR-Cas system
Visualization of the CRISPR-Cas system (Image Courtesy: Drug Target Review)

The CRISPR-Cas9 system

Finally, the CRISPR and the Cas9 enzyme create a powerful immune system tool we know as the CRISPR-Cas9. It is widespread among bacteria- we can find it in over half of all genomes, and 90% of archaea genomes. It is the cell’s primary defense system against bacteriophages, which makes it essential for bacteria’s life and evolution. How is that mechanism used in gene editing then?

Mechanism of Genome Editing With CRISPR

Molecular Scissors

CRISPR-Cas9 technology enables scientists to remove, alter, or add DNA sections. The Cas9 protein acts as molecular scissors. It cuts the strands of DNA at a particular location, enabling to introduce the change. Afterward, guide RNA (gRNA), consisting of the small piece of specifically designed CRISPR RNA fragment within a more extended sequence. The longer part binds to the matrice DNA, whereas the CRISPR guides Cas9 to the right place in the genome, just like it does in bacteria and archaea.

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The CRISPR part is complementary only to one region in the genome, so it will not bind anywhere else, making the technology precise. When Cas9 finds the complementary fragment, it cuts across the DNA. The cell recognizes the cut as damage and repairs it, combining the mutation (larger piece) with its DNA. The result is a functioning genome with a specific mutation.

Mechanism of CRISPR-Cas9
Mechanism of CRISPR-Cas9

Application of the CRISPR-Cas9 technology

DNA contains genes- detailed information about proteins and their creation. The genetic expression is when specific structures translate information, enabling the creation of various molecules. Combined, the information in the DNA and factors impacting expression create us. DNA consists of information about every single protein we are built of- its structure, location, ways of expression, functions, and many, many more. Therefore, altering the DNA changes the organism on the molecular level. That makes the CRISPR-Cas9 such a powerful tool. Using the right sequences, we can change the way organisms are and customize them for our needs. Of course, there are challenges regarding which genes to use, where to insert them, and how they will affect the organisms.

Nobel Prize 2020 and Controversy

Nobel Prize 2020

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Marie Charpentier and Jennifer Doudna- pioneers of the CRISPR-Cas9 method. Charpentier is a French professor, microbiological researcher, and founder of the Max Planck Unit for the Science of Pathogens- an independent research institute. Jennifer Doudna is a chemistry professor at the University of Berkeley, California. She is also an investigator with the Howard Hughes Medical Institute. Their award is the first science Nobel Prize won by two women.

Founders of CRISPR-Cas9 method were awarded with the Nobel Prize 2020
Founders of the CRISPR-Cas9 method were awarded the Nobel Prize 2020 Image Courtesy: Scroll

Controversy

The two women aren’t the only ones claiming they invented the method. The team from MIT claims they discovered it independently. The two teams are now suing each other for rights to the patent. It all comes down to who can prove to be the first to invent the CRISPR-Cas9 method.

Gene-editing technology is one of the most promising and one of the most controversial in modern sciences. People are scared of ‘playing God’, manipulating children’s genomes, or creating a superior new species. Whereas it certainly comes with great responsibility and possible threat, it can also massively improve our lives and understanding of the world. “Nothing in life is to be feared; it is only to be understood,” said Marie Curie. With that thought, we should use the CRISPR-Cas9 to make the world better, understanding the risks and responsibility that comes with power.

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