How Does CRISPR Work?

History OF CRISPR: Where It All Began

The year was 1987 when Yoshizumi Ishino, a Japanese scientist, discovered a series of

repetitive DNA sequences Patterns of DNA that are copied and occur in the gene multiple times

. He and his team could not understand what these sequences did. For a long time, it remained a mystery. But over the years, many scientists began piecing together the information. And cut to 2020, Jennifer Doudna and Emmanuel Carpentier co-won the Nobel prize in chemistry for their ground-breaking work on

CRISPR-Cas9 A technique to modify or change the genome.

. CRISPR-Cas9 has come a long way since its accidental discovery in 1987 and its journey is worth documenting.

Edit It, Till You Make It!

If you have ever written a blog or an article, you know that editing is one of the critical processes to make it impactful. Similarly, genome editing is a set of technologies that can make changes to an organism’s genetic information. As the name suggests, genome = genetic information and editing = making changes. These technologies can add, delete, or modify our genes. And CRISPR-Cas 9 is one of them.

CRISPR, CRISPR, Can you help me fight this Virus?

Surprisingly, CRISPR-Cas 9 originated in bacteria. It evolved as an

adaptive immune systems.

Bacteria used this immune system to fight off foreign entities like viruses. When a virus infects a bacterium, the bacterium captures its DNA. The viral DNA is then inserted into the bacteria’s own DNA. In this way, the bacteria ‘remembers’ the virus. How does it ‘remember’ the virus? The bacteria’s memory can be thought of as Google search history. Every time we search for something in Google, the computer remembers it. Next time we type in the same query, we can get the results quickly. Similarly, the viral invasion is the ‘search query’ and the bacteria’s memory of it is the ‘google search history.’ The next viral invasion is hence met with greater force, and it is quickly dealt with.

CRISPR: My Mechanism Is ‘CRISP’ & Effective

CRISPR Stands for ‘Clustered Regularly Interspaced Short Palindromic Repeats.’ Big name! But at the core of it, this system contains two important elements: an enzyme called Cas9 and a type of

RNA Genetic information contained in the cell

called guide RNA. To better understand the working of CRISPR, imagine yourself in a barber’s shop. The barber uses scissors (Cas9) to cut your hair (

the DNA Genetic information contained in the cell

) and give it a stylish shape. But the barber also needs an efficient pair of hands (or in the case of CRISPR-Cas9, the guide RNA or gRNA) to guide this process. In a barber’s shop, you have plenty of options to modify your hair. You can cut your hair, give it a different color, or add hair extensions. Similarly, CRISPR-Cas9 can be used to cut sections of DNA, cause changes to the DNA already present, or add segments of DNA. At this point, you might wonder, how does the gRNA know how to guide the Cas9 enzyme? It is because RNA and DNA show

complementary binding A type of specific interaction between base pairs of DNA.

. DNA is made up of four building blocks called nucleobases: Adenine(A), Guanine(G), Thymine(T), and Cytosine(C). Whereas, RNA is made up of Adenine(A), Guanine(G), Uracil(U), and Cytosine(C). Complementary binding is a pairing game played between these nucleobases. Adenine can only pair with Thymine (in DNA) or Uracil (in RNA), and Guanine only pairs with Cytosine. So, when the gRNA, which contains a specific sequence, reaches the DNA, it looks for its complementary partner. As soon as it finds it, the gRNA guides the Cas9 to that specific site on the DNA. Cas9 does its job of modifying the DNA at this site. For this reason, Cas9 is also called ‘molecular scissors.’

Where Do We Use CRISPR?

CRISPR is like a wizard’s wand: it can make magic happen. It can treat

genetic diseases Illnesses caused by a change or aberration in a person’s DNA

like cystic fibrosis, sickle cell anemia, and Huntington’s disease. It has the potential to cure cancer. It can also be used to change the color of flowers. A few years ago, scientists changed the color of a flower called Japanese morning glory, or Asagao, from violet to white. Interestingly, CRISPR has also been used to understand the effect of climate change on corals. It can help guide conservation efforts as well.

SOOO, What’s New?

A new approach to delivering CRISPR to cancer cells has become the talk of the bio-town. It involves enclosing the CRISPR-Cas9 in something called a

lipid organic compounds made of fatty acids, that in turn make up fats, oils, and waxes

nanoparticles A tiny particle with size less than 100 nanometres

. These nanoparticles can then be specifically targeted to cancer cells. This ensures that only cancer cells are killed, and other, non-cancerous cells aren’t affected. Unlike other methods of cancer treatments, this technology has no side effects and is very effective at killing cancer cells. The new CRISPR technology is called CRISPR-LNP

CRISPR & COVID: A Cut And A Sneeze

With COVID-19, one of the hurdles has been the time taken by testing. But all that can be changed with the combined power of CRISPR and smartphones. This CRISPR-based diagnostic technique involves Cas13 protein instead of the usual Cas9. Cas13 is used because the

SARA-CoV-2 Virus that causes COVID-19

virus contains RNA as its genetic material and Cas13 can cleave RNA. Cas13 is also attached to a molecule that emits light when it is cut. The sample to be tested is placed in a device attached to a smartphone. Cas13 is added to it. If the sample contains RNA, Cas13 is activated. Activated Cas13 activates the light-emitting molecule. The resulting light indicates the presence of RNA and confirms infection with COVID-19.

CRISPR Ain't Always The Answer

CRISPR has plenty of benefits. Not only can it save or improve lives, it can also be used for other, non-medical purposes. For example, it could be used to change your eye color, hair color, and so on. Really, with CRISPR the genome is just a biological canvas. But let’s not get ahead of ourselves. Because even CRISPR has major downsides. The entire scientific community was left in shock when scientist He Jiankui announced the birth of twin baby girls. The genome of the twins was apparently modified using CRISPR to rid them of the virus

HIV Human Immunodeficiency Virus, the virus that causes the disease AIDS.

. But the gene Mr. Jiankui edited, called CCR5, to make them HIV-free also has significant functions when it comes to fighting other diseases. Hence, when these babies were introduced to the world, it led to outrage among the research community and questions were raised regarding the health of the babies. Several wondered what it meant for the babies’ future. This also serves as a lesson for all the aspiring researchers out there. An innovation that seems like the solution to one problem could lead to several other issues.

Glossary

CRISPR-Cas9 A technique to modify or change the genome.

Adaptive Immune System: A system that helps bacteria evade viruses. DNA/RNA: Genetic information contained in the cell. Complementary binding: A type of specific interaction between base pairs of DNA. Nanoparticle: A tiny particle with size less than 100 nanometres. SARA-CoV-2: Virus that causes COVID-19. HIV: Human Immunodeficiency Virus, the virus that causes the disease AIDS. Genetic diseases: Illnesses caused by a change or aberration in a person’s DNA Lipids: organic compounds made of fatty acids, that in turn make up fats, oils, and waxes Repetitive DNA sequences: Patterns of DNA that are copied and occur in the gene multiple times