"The revolution of Gene Editing: Unravelling the power of CRISPR-Cas9 Technology"

“The wheels on the boat go round and round?”
Assume that you are singing your favourite song and you accidentally misspoke a
song lyric. This can easily be fixed by searching the lyrics on a search bar, detecting
the error, and either correcting or removing the lyric mistake. Essentially, this concept
can somewhat be implemented in our DNA called CRISPR-Cas9. The word CRISPR
or “Clustered Regularly Interspaced Short Palindromic Repeats”, is a distinguishing
feature of a bacterial defence system that forms the foundation for CRISPR-Cas9
genome editing technology. It is a type of technology used to selectively alter the
DNA of living organisms.

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How does it work?
The CRISPR-Cas9 system works by cutting a DNA
sequence (determining the order of the four chemical
building blocks called bases that make up the DNA
molecule) at a specific genetic location and deleting or
inserting new DNA sequences. The diagram to the right
shows how the CRISPR-Cas9 editing tool works with the
stages.
For this system to function, it requires two vital molecules
for a change/mutation in the DNA: An enzyme called Cas9
and a piece of RNA called guide RNA (gRNA).
First, scientists identify the specific DNA sequence they
want to modify. Then, a guide RNA, which is a
pre-designed RNA sequence that belongs to a longer RNA
scaffold, is designed to bind with a complementary DNA
sequence. This means that the guide RNA will only bind to
the target sequence and no other regions of the
genome/DNA. After, the gRNA ‘guides’ the Cas9 enzyme
to the right part of the genome. This enzyme acts as a pair
of ‘molecular scissors’ that cut the two strands of DNA at a
specific location in the genome so that bits of DNA can be
added or removed. Scientists can take advantage of this
system so that they can edit the existing DNA by either
modifying, deleting, or inserting new sequences.

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The discovery of Cas9
CRISPRs were adapted for use in the laboratory from naturally occurring genome
editing systems found in archaea (and later in bacteria). During May 2005, Alexander
Bolotin, a French (INRA) microbiologist was studying the bacteria “Streptococcus
thermophilus”. It had just been sequenced, revealing an abnormal CRISPR locus.
Although the CRISPR arrangement was similar to previously reported systems, it
lacked some of the known Cas genes and
contained newly identified Cas genes instead,
including one encoding a large protein predicted to
have nucleus activity, which is now known as
Cas9. By having nucleus activity, it meant that
having a Cas9 protein, guided by an RNA
molecule, fundamentally can cause a
double-strand break to a complementary DNA. The
discovery of the CRISPR-Cas system unlocked a
gateway of possibilities for scientists to strengthen
the bacterial immune system.

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Why is it important?
With the higher demand for healthcare, the
CRISPR-Cas9 mechanism allows bacteria to store
genetic information from past viral infections in return
for a flexible immune system. The use of CRISPR
Technology can cure cancer, blindness, AIDS, and
COVID-19. CRISPR can also be implemented in
animals by making disease-resistant chickens and
pigs, and foods with disease-resistant crops such as
wine grapes. These are only a few of the many
concepts CRISPR can be used for.

What problems could arise?
However, the use of the CRISPR-Cas9 system faces many challenges. One
challenge is the occurrence of off-targeting modifications. The Cas9 enzyme can go
‘off-target’, meaning that it may act on DNA sequences that are similar but not
identical to the target site, causing undesired mutations or modifications in the DNA.
This consequence can also occur if DNA is damaged and is left to repair the cell
alone. This raises ethical concerns about unintended consequences and may lead to
potential health risks, or ecological impacts in an ecosystem.

​Whilst the accomplishments of
CRISPR-Cas9 lead scientists to
further develop potential scientific
and medical advancements,
further research and investigation
need to be done, and public
disclosure should be taken into
account to discuss the ethics of
the CRISPR-Cas system before
establishing it. So, the next time
you sing a song, make sure to
get your lyrics right!

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Work Cited:

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Broad Institute (2018a). CRISPR Timeline. [online] Broad Institute. Available at:
https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timelin
e.

Broad Institute (2018b). Questions and Answers about CRISPR. [online] Broad
Institute. Available at:
https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-an
d-answers-about-crispr.

Fernández, C.R. (2021). Eight diseases CRISPR technology could cure. [online]
Labiotech.eu. Available at:
https://www.labiotech.eu/best-biotech/crispr-technology-cure-disease/#thefutureofcri
sprtechnology.

Genome.gov. (n.d.). A Brief Guide to Genomics. [online] Available at:
https://www.genome.gov/about-genomics/fact-sheets/A-Brief-Guide-to-Genomics#:~:
text=What%20is%20a%20genome%3F.

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Heidt, A. (2020). CRISPR Gene Editing Prompts Chaos in DNA of Human Embryos.
[online] The Scientist Magazine®. Available at:
https://www.the-scientist.com/news-opinion/crispr-gene-editing-prompts-chaos-in-dn
a-of-human-embryos-67668.

KQED. (2017). Watch Real Moving Images of CRISPR/Cas9 Cutting DNA. [online]
Available at:
https://www.kqed.org/futureofyou/437298/watch-crisprcas9-in-action-in-this-real-time
-movie-of-dna [Accessed 16 Nov. 2023].

Mayo Clinic (2018). CRISPR Explained. YouTube. Available at:
https://www.youtube.com/watch?v=UKbrwPL3wXE&ab_channel=MayoClinic.

Rasul, M.F., Hussen, B.M., Salihi, A., Ismael, B.S., Jalal, P.J., Zanichelli, A., Jamali,
E., Baniahmad, A., Ghafouri-Fard, S., Basiri, A. and Taheri, M. (2022). Strategies to
overcome the main challenges of the use of CRISPR/Cas9 as a replacement for
cancer therapy. Molecular Cancer, [online] 21(1).
doi:https://doi.org/10.1186/s12943-021-01487-4.

Society, M. (2023). Archaea | What is microbiology? [online] microbiologysociety.org.
Available at:
https://microbiologysociety.org/why-microbiology-matters/what-is-microbiology/archa
ea.html#:~:text=Archaea%20are%20a%20group%20of.

YourGenome (2022). What is CRISPR-Cas9? [online] yourgenome.org. Available at:
https://www.yourgenome.org/facts/what-is-crispr-cas9/.

kiowacountypress.net. (n.d.). Scientists are on a path to sequencing 1 million human
genomes and use big data to unlock genetic secrets | Kiowa County Press - Eads,
Colorado, Newspaper. [online] Available at:
https://kiowacountypress.net/content/scientists-are-path-sequencing-1-million-human
-genomes-and-use-big-data-unlock-genetic.