Image: Dr Mohamed Fareh from the Peter MacCallum Cancer Centre was able to flip his research into children’s cancer treatments to new methods for antiviral drugs.
CRISPR is a powerful gene-editing tool used by bacteria in their arms race against viral infection. The term was coined by Spanish microbiologist Francisco Mojica in the 1990s; by 2010, microbiologists had shown that the CRISPR-associated protein CRISPR-Cas9 acts as molecular “scissors” to precisely cut and edit DNA.
In 2015, Russian-US PhD student Sergey Shmakov identified CRISPR-Cas13, a protein that edits RNA rather than DNA, reducing the risk of unintended effects on non-targeted genes.
When Cas13 was discovered, Dr Mohamed Fareh was a postdoctoral researcher at the Delft University of Technology in the Netherlands.
“I was really interested in understanding the molecular mechanisms bacteria deploy to fight invading viruses,” he says.
Fareh joined Melbourne’s Peter MacCallum Cancer Centre (Peter Mac) in 2018. In 2019, he and Professor Joe Trapani collaborated with the Children’s Cancer Institute in Sydney to show that Cas13 could successfully eliminate the abnormal RNA that drives a range of childhood cancers.
From Cancer to COVID-19
When the COVID-19 pandemic hit in early 2020, Fareh had a “bold and wild idea” to reprogram the CRISPR-Cas13 tool to silence the SARS-Cov-2 virus behind the disease.
“SARS-Cov-2 is an RNA virus, so it was a perfect target,” he says.
When the SARS-Cov-2 viral sequence was released by scientists in Wuhan, Fareh and his team at Peter Mac were able to design guide RNA that reprogrammed the CRISPR tool to target small, non-replicating segments of the SARS-Cov-2 genome.
Fareh then approached Professor Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, co-located with Peter Mac at the University of Melbourne. Together with virology postdoctoral researcher Dr Wei Zhao, Lewin and Fareh were able to show that CRISPR could achieve more than 90 per cent suppression of the live virus in infected mammalian cells.
Game-changer for pandemics
The CRISPR-Cas13 tool targets the SARS-Cov-2 genome and cuts it, stopping the virus from replicating. The researchers have demonstrated that the CRISPR tool remains robust whencombatting viral mutations.
“Even if the virus mutates, the tool remains effective. We can target diff erent strains with a single drug,” Fareh says.
He says the work is a game-changer for future pandemics. Traditional antiviral drugs target proteins and are extremely challenging to develop in a short period of time. In contrast, the CRISPR-Cas13 tool can be reprogrammed rapidly to fight other viruses such as influenza, Ebola, HIV and many more — as long as the virus’ genome is known.
“We can quickly reprogram it to target any new virus that may emerge in the future,” Fareh says.
As scientific understanding of CRISPR and its associated proteins evolves, more life-saving treatments will be developed. Fareh says there is a continuum between basic and translational science at Peter Mac and the Doherty Institute.
“When you master basic research, it gives you unique opportunities to translate it to something important, like targeting viral or tumour cells,” he says.
Writer: Nadine Cranenburgh