Introduction

Have you ever wondered if there was a way we could change our DNA ? Well, Jennifer DOUDNA
and Emmanuelle CHARPENTIER have thought about it and they found a system in 2012 that
revolutionized the world of genetics. The two women that won the Nobel price of Chemistry in
2020 for their discovery, developed a technology called CRISPR-Cas9 which stands for «
Clustered Regularly Interspaced Palindromic Repeats » . That technology consists of aiming at a
precise part of a gene and editing it. It is useful for curing dysfunctional genes that cause severe
diseases like cancer or disabilities like autism. But how does it really work ? What really is
CRISP-Cas9 and how can it impact the world of science ?
To answer that question, we’ll explain first the function of this enhancement, then, in a second
part, we’ll see precisely how it works, afterwards in a third part, we’ll deal with the potential
risks of CRISPR-Cas9, and finally, we’ll present a more future-oriented perspective of the
technology.

• Plan en 4 parties:
1. Qu’est ce que c’est?
2. Comment on l’utilise ?
3. Quel sont les risques?
4. Quel est l’avenir du CRISPR-Cas9 ?

CRISPR =(Clustered Regularly Interspaced Short Palindromic Repeats)

I. Qu’est ce que c’est ?

So what exactly is Crispr-cas9? Well, Crispr s is a DNA sequence originally discovered in certain
bacteria and derived from a virus that once infected them. In other words, it's a kind of "genetic
memory" of past infections. Crispr's role in bacteria is to act as an adaptive immune system.
When a bacterium is exposed to a virus, it can integrate fragments of the virus' DNA into its own
Crispr sequences, thus creating RNA (ribonucleic acid, a chain of nucleotides used to synthesize
proteins. ) which then guide a "Cas" protein to precisely cut the virus's DNA and thus neutralize
it.
As for "cas9", this is the protein that creates the famous DNA scissors. Its cutting activity is
guided by a guide RNA, which is designed to be complementary to the DNA sequence the
researchers want to modify. In other words, Cas9 is programmable to target any specific DNA
sequence according to its associated guide RNA sequence.
It is the combination of these two elements, Crispr and Cas9, that creates the famous DNA
scissors.
II. Comment on l’utilise ?

First, the scientists conceive a RNA guide that matches the target gene’s DNA sequence. Then, it
gets paired up with the Cas9 protein, the one design to cut the targeted DNA sequence, so when
injected inside the cell, it is led by the RNA guide to the sequence to edit.

When it reaches the specific DNA site, thanks to the RNA guide, the Cas9 protein cuts the
sequence so it’s not functional anymore. Automatically, the DNA sequence tries to repair the
broken gene. There are two ways of repairing :

 NHEJ (Non-Homologous End Joining) the way of repairing that induces a lot of
mutations at the cut site which results the gene to not function anymore.

 HDR (Homology-Directed repair) the way of repairing the gene by modifying it with
specific mutations so it can be functional instead of inactive. It’s a more precise way of
editing a DNA sequence.

Scientists can strongly influence the outcome of the repair, but they can’t guarantee which way
will be chosen by the DNA sequence. Once repaired, either the gene is knocked-out or it’s
modified.

Furthermore, this way of correcting a defective gene is the same for every application. It might
vary from one specie to another, but for the human race, it’s the same pattern. Some treatments
are already available through therapy in the UK but for now on, it’s still on trials.

II. Les risques ?

This new DNA-cutting technique is nonetheless a source of concern, due to the potential risks it
could present, particularly in terms of embryo modification, genetic mutation or the use of these
genetic scissors by unqualified persons.
Indeed, these DNA scissors could make it possible to genetically modify embryos by changing
certain characteristics of their genes. The quest for the "perfect child" would then be possible.
We could choose the color of his eyes, his hair and even influence the strength of his immune
system. In 2020, a Chinese scientist was condemned after giving birth to two "CRISPR Babies":
girls whose genome had been modified to resist HIV.
The second risk concerns the possibility of genetic mutation. After several trials, notably on
mice, scientists realized that Crisp-Cas9 had caused mutations in places that had not even been
subjected to the scissors. This led to the activation and deactivation of certain genes carrying
more or less important information, which could have serious consequences for a species in the
long term.
Finally, it is now possible to buy Crisp-Cas9(150) kits directly from the Internet, enabling
experiments to be carried out at home without having to have the qualifications required to
master the method.
Crisp-cas9 could therefore represent a potential danger for tomorrow's man if misused. The CIA
has even classified the process as a potential "weapon of mass destruction".

III. Les perspectives dans le future ?

The CRISPR-Cas9 technology is expanding and many scientists work on improving the
treatment. They assess its safety and functionality so CRISPR-Cas9 can be used in some medicine
in the future.

Nowadays, some scientists are working on a better editing tool than Cas9, like Cas12 or Cas13,
which allows the DNA sequence to be directly modified and better controlled. So perhaps in the
future, we could use CRISPR-Cas12 or 13 and have better control over curing defective genes.

However, to what extent can we modify genes ? maybe in the future some parents can ask to
design their own baby based on their liking which can bring up some questions eventually. Won’t
that lead to a implemented social standard among genetically-modified born babies ? Moreover,
won’t that enforce economical disparities within people who can afford the treatment and those
who don’t ? Where is the line not to cross ? All of these questions can emerge from this intricate
technology ultimately.

IV. Conclusion :

To conclude this presentation and answer our specific question, we can say that Crispr-cas9
represents a real revolution in the world of genetics, and that in the near future it could
drastically improve the living conditions of mankind and his environment. Nevertheless, the many
risks it presents, including potential abuse, mutation and misuse, could have drastic
consequences for tomorrow's world. This new technology must therefore be used with extreme
caution to ensure that it does not present any risks to the survival of terrestrial species. Thank
you for listening.
Sites à visiter :

 Prix Nobel de chimie : 3 questions sur les ciseaux génétiques (CRISPR-CAS9) - Top Santé
(topsante.com)