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S tudent Voice

therapeutics, we are still in early days of its research and some
issues presented are yet to be solved.

Delivery
Getting CRISPR/Cas to play nicely inside lab flasks is one thing
but guiding it to those tissues or cells within a living organism is
another challenge altogether. The hitch? While CRISPR/Cas13
works potently once in a cell, getting into the cell proves to be
a hurdle. It struggles to pinpoint where the problem cells are,
and it also struggles to get into those cells due to the size of
the system. Luckily, emerging methods like lipid nanoparticles
could hold the key to unlocking efficient delivery straight to
desired tissues.

Immunogenicity
Apart from the difficulties in delivery, as the CRISPR/Cas system
originated from bacteria, our own human immune system isn’t
always welcoming to this foreign system. If our immune system
destroys Cas13 proteins before they can silence cancerous
RNAs, this will nullify the intended therapeutic outcome. We
are still in the dark about those long-term side effects on our
To simplify things, crRNA works like a GPS system that is immune system, urging us to move forward carefully.
paired to the Cas13 missiles. When a foreign RNA sequence is
detected, crRNA guides Cas13 to destroy the invading RNAs Off-target effect and safety concerns
(Graph 3). In addition, when another bacteriophage bearing To be able to be approved for human therapeutics, CRISPR/
different virulent RNA infiltrates, CRiSPR-Cas13 can also adapt Cas13 needs a laser-like precision with its target RNA -- even
by generating an alternative crRNA, precisely tailored to match 0.01% of off-targeting can be proven to be detrimental.
the RNA sequence of the newfound invader. However, researchers have shown that crRNA binding is a bit
forgiving and can tolerate a few mismatches. This means Cas13
As RNAs are the precursors of proteins, if we can cleave and proteins can unintentionally silence RNAs not meant to be
destroy tumour-driving RNAs, we can stop different types of affected. This highlights the need to systematically study the
cancer at their roots. By engineering CRISPR GPS (artificial off-target effects from Cas13 proteins to ensure their therapeutic
crRNAs) to target RNAs of interest, we can unleash Cas13 safety.
proteins to specifically destroy cancerous RNA without harming
healthy cells lacking those cancer mutations. This game- Yet hope glimmers on the horizon. These challenges spark
changing RNA-targeting system promises precision, adaptability innovation and pave the way for improvements. Our research
and cost-effectiveness – gone are the days of chasing cancer group (Fareh Group of Trapani Lab, Peter MacCallum Cancer
mutations, we can now easily tailor the tool to fit the specific Centre) is already smashing barriers, fine-tuning the level of
needs of specific patients. precision-targeting, and devising solutions to tackle mismatch
tolerance. Plus, we are pioneering lipid nanoparticle technology
CRISPR and its therapeutic future for in vivo deliveries. These strides bring us one step closer
Like any superhero, CRISPR/Cas13 isn’t without its kryptonite. to the application of CRISPR/Cas13 for efficient and safe
While it offers a lot of potential for both research and clinical personalised cancer therapies.

J anet Clarke Hall 29