Issue 2 Article 6

Nobel Intentions: CRISPR

25/2/20

By:

Wang Zihan

Edited:

Crystal Tay Yuan Ying

Tag:

Biotechnology and Engineering

A doctor brings over a tablet, with information about millions of embryos, each with genetic information detailing the child’s intelligence, chance of diseases, disposition and future appearance. You are allowed to edit any of the information as you please. Within a few minutes, you have chosen a baby, a child to suit your exact needs and develop exactly the way you want them to.

These are designer babies, or babies genetically engineered in vitro for specially selected traits. This used to be a dream of sci-fi enthusiasts, some distant reality to be scoffed at. Yet, the discovery of the CRISPR-Cas9 system in 2012 which could be used to edit DNA made waves around the world, as it unlocked an entire new frontier in biotechnology.

CRISPR’s discovery

The discovery of CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, was unexpected. While French Professor Emmanuelle Charpentier was researching the harmful bacteria Streptococcus pyogenes, she discovered a previously unknown molecule, tracrRNA, which led her to find the bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

After publishing her findings in 2011, she initiated a collaboration with Jennifer Doudna, an American biochemist. Originally, the CRISPR/Cas system was used to recognise DNA from viruses, where the system acts as genetic scissors to cut and edit various segments of the gene. However, in 2012, Charpentier and Doudna proved that these scissors could be controlled to cut any DNA molecule at a predetermined site.

Together, they succeeded in creating the bacteria’s genetic scissors in a test tube and simplifying the scissor’s molecular components so they were easier to use. Using these, researchers can precisely edit the DNA of living organisms. Since then, the discovery of this tool has opened innumerable new possibilities in biological research.

In 2020, Charpentier and Doudna were awarded the Nobel Prize in Chemistry.

How CRISPR works

CRISPR is a family of DNA sequences found in simpler organisms such as bacteria and archaea. It is derived from DNA fragments of bacteriophages (a type of virus) that had previously infected the organism, and is used to detect and destroy DNA from similar bacteriophages during subsequent infections. CRISPR provides acquired immunity, similar to a vaccine. Humans take advantage of the natural missile homing system of the bacteria to apply on other organisms.

Cas9 is an enzyme that uses CRISPR sequences as a guide to recognise and open up specific strands of DNA that are complementary to the CRISPR sequence. It is responsible for cleaving the target DNA to form a double-stranded break and is called a genetic scissor.

CRISPR-Cas9 can be used to edit genes within organisms. Like a missile homing system, it identifies its target and “attacks” it. Using the DNA sequence of CRISPR, a guide RNA (gRNA) is coded into CRISPR-associated (Cas-9) proteins. Subsequently, Cas-9 proteins target a specific gene, cutting the gene up and replacing it with the gRNA.

Because the gRNA has RNA bases that are complementary to those of the target DNA sequence in the genome, CRISPR-Cas9 is highly specific and precise. In theory, it should only be binding to the target sequence and no other regions of the genome, making it extremely useful in research.

The future of CRISPR

Since CRISPR’s groundbreaking emergence, plant scientists have successfully engineered crops resistant to mold, pests, and drought. These organisms have been coined as ‘GM crops’, and allows farmers, consumers and producers alike to reap the benefits of a genetically enhanced plant. Meanwhile, in medicine, clinical trials for innovative cancer treatments are in progress, bringing the long-held hope of curing inherited diseases closer to reality. In 2023, Casgevy, a treatment to cure sickle-cell disease and beta thalassemia, became the first drug using CRISPR to be approved by the US FDA.

However, CRISPR is not without its challenges. Many bioethical concerns have been raised about using CRISPR to edit human genomes, especially in human embryos. Chinese scientist He Jiankui became infamous after he announced that he had successfully edited the genomes of twins to confer genetic resistance to HIV, leading to international backlash and even a prison sentence.

The discovery of CRISPR-Cas9 has no doubt been revolutionary, marking an epoch in the history of life sciences. Yet, using the tool carelessly could result in disastrous consequences. Even Doudna, one of the scientists who discovered CRISPR, warned of its dangers in a 2020 interview with the New York Times. As we stand on the brink of a genetic revolution, the true test of CRISPR’s legacy will not be in its power, but in how we choose to wield it.

References:

Issue 4 - Apr 2025

Nobel Intentions: CRISPR