CRISPR Technology and Potential Applications

- Overview

A decade ago, we saw a breakthrough in modern biology. Two American scientists have discovered that the manipulation of the Cas9 protein has produced a genetic technology comparable to a science fiction movie: CRISPR. 

CRISPR was discovered by Dr. Jennifer Doudna (University of California, Berkeley) and Dr. Emmanuel Charpentier (Max Planck Pathogen Science Unit). The two scientists who pioneered revolutionary gene-editing technology are the recipients of the 2020 Nobel Prize in Chemistry.

Think of it as a pair of molecular scissors capable of cutting and editing DNA in humans, animals, plants, bacteria and viruses. The potential is enormous, covering anything from eliminating inherited diseases to producing crops that can withstand climate change. However, like any other new technology, CRISPR has its challenges. One of the main challenges was making the technique as efficient as possible and making sure the scissors only cut where we wanted.

A genome is an organism's complete set of DNA, including all its genes. Each genome contains all the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells with a nucleus. 

CRISPR technology is a simple and powerful genome editing tool. It enables researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of disease, and improving crops. However, its promise also raises ethical questions. 

- CRISPR Technology

CRISPR is a promising gene editing technology that enables efficient and precise genome modification. The CRISPR/Cas9 system will enable scientists to become designers, removing previous technological limitations and calling for a new era of synthetic biology. 

This versatile gene-editing technology has developed rapidly since its adaptation by Drs. Doudna and Charpentier. It has been adapted for many different purposes, including RNA editing, base and primary editing, real-time imaging, and diagnostics. It has been used to edit DNA in a variety of organisms, including humans. 

In 2019, the first CRISPR clinical trials began, in which cells were harvested from sickle cell disease (SCD) patients, edited in vitro, and then injected into the body — an approach known as cell therapy. 2020 saw the first direct injection of CRISPR therapy into human patients following a successful SCD cell therapy trial. This technique, called gene therapy, is used to treat inherited blindness.

- The Potential Applications of CRISPR Technology

The potential applications of CRISPR technology are limitless. In petri dishes and animal models, researchers used CRISPR to fix major genetic errors, such as those that cause muscular dystrophy, cystic fibrosis and Fragile X syndrome. They have used the technology to engineer pigs to grow organs for people in need of transplants. Other efforts are underway to eliminate HIV infections, design smarter antimicrobials and control disease-carrying mosquitoes. But don't expect a CRISPR pill to solve any of your problems anytime soon.

Over the past decade, we have taken a big step toward being able to edit genomes. Now we are making our approach better, safer and more efficient. The latter also supports green transitions, such as genome modifications, such as a reduction in the number of batteries used in production, that can use resources more cost-effectively.

[The CRISPR/Cas9 Genetic Scissors - The Royal Swedish Academy of Sciences]

- CRSPR: A Precise Gene-editing Tool

The ability to cut DNA where you want has revolutionized the life sciences. CRISPR - repetitive pieces of DNA that bacteria use to protect themselves from invading viruses. Viruses can infect bacteria, just as they can infect you and me. When we have a viral infection, our immune system produces antibodies against the virus so we can respond quickly the next time we are threatened.  

For many bacteria, CRISPR is an immune system. When infected, bacteria collect fragments of viral code and stuff them into their own genomes for safekeeping. These sequences act as a kind of immune memory, giving bacteria the molecular fingerprint of the virus that infects them. If the same virus reappears, the bacteria recognize it and release a DNA-cutting protein called Cas9 to sever the invader's genetic code. That's why many refer to this technology as CRISPR/Cas9. 

Today, CRISPR is widely known as a precise gene-editing tool, but it took scientists years to figure out what it is and how to harness its potential.

- Guide RNA

So how does CRISPR work? First, scientists will design a piece of synthetic RNA, called a guide RNA. It is then linked to the Cas9 protein that will perform the task of cutting DNA. Guide RNA scouts for matching DNA sections. Once the guide RNA finds the correct location, Cas9 cuts the DNA strand. Now, scientists can insert any synthetic DNA fragment into the vacated position.

If Cas9 and the guide RNA hit the target, scientists call it the target; if they hit the other place, they stray from the target. 

Today, CRISPR is mainly used in the medical context to study how genes and drugs work in the laboratory, but it is still not widely used in human therapy. In the long term, however, the idea is to use CRISPR to treat certain genetic diseases.

- The History and Discovery of CRISPR

CRISPR was discovered by Dr. Jennifer Doudna (University of California, Berkeley, above left) and Dr. Emmanuel Charpentier (Max Planck Pathogen Science Unit, Berlin, right). Their seminal paper, which revealed that the CRISPR-Cas9 bacterial immune system can be repurposed as a gene editing tool, was published in the journal Science in 2012. 

It wasn't until 2020 -- after it was adopted by labs around the world -- that Doudna and Charpentier won the Nobel Prize in Chemistry for their discovery, becoming the first all-female team to do so. 

Other key contributors include Feng Zhang of the Broad Institute of MIT and Harvard University, Cambridge, MA, who pioneered the use of CRISPR in eukaryotic cells and discovered new Cas variants, and George of Harvard Medical School, Boston, MA Church was the first to demonstrate its use in human cells, and Virginijus Siksnys, a biochemist at Vilnius University in Lithuania, independently discovered the ability of CRISPR to edit the genes of other organisms.

[More to come ...]