Dr Yexuan Deng, Dr Eddie La Marca and Wei Jin, all co-lead authors on the paper
What is Gene Editing?
Our bodies consist of trillions of cells, each containing a set of instructions called genes. These genes are written in a special code called DNA, which determines how cells grow and function. When this code has errors, diseases like cancer can develop.
To solve this problem, researchers developed CRISPR, a powerful tool that acts like a molecular “search and edit” function for DNA, and more recently, RNA – the cellular messenger that carriers out DNA’s instructions. The key to this technology is a special protein called a Cas enzyme, which acts like molecular scissors, cutting and modifying specific DNA or RNA sections. By editing faulty genes, researchers aim to find better ways to treat cancer.
How is this Study Advancing Gene Editing?
Until now, most research has relied on the Cas9 enzyme for gene editing. This study is the first to demonstrate Cas12a usage in a pre-clinical cancer model. Cas12a offers distinct advantages, including the ability to edit multiple genes at once with high precision.
Using this tool, our researchers identified genes that accelerate lymphoma growth. They achieved this by using a specially designed set of genetic “libraries” tailored to work with newly established Cas12a-compatible mice. This allowed them to scan the entire genome (the complete instruction manual for an organism) and pinpoint the genes contributing to cancer.
Dr Eddie La Marca, a researcher at ONJCRI and WEHI, explains:
“This is the first time Cas12a has been used in pre-clinical models, and it will greatly enhance our ability to study cancer. Unlike Cas9, Cas12a allows us to delete multiple genes at once with extremely high efficiency.”
By combining Cas12a with other gene-editing tools, the team also created a system that can both delete faulty genes and activate beneficial ones at the same time, a technique known as multiplexed gene editing.
The Future of Gene Editing in Cancer Treatment
Professor Marco Herold, Chief Executive Officer of the ONJCRI and Head of the La Trobe University School of Cancer Medicine, emphasised the significance of this breakthrough:
“We are certain that this work will encourage other research teams to adopt this Cas12a pre-clinical model, which, combined with screening libraries, offers a powerful new set of gene-editing tools to enhance our understanding of the mechanisms behind many different cancers.”
Professor Herold’s team at the ONJCRI is now focused on developing methods to deliver CRISPR-based therapies to patients, bringing gene-editing technology one step closer to being used in novel cancer treatments.
“This Cas12a pre-clinical model will be key in advancing our understanding of how CRISPR tools can be applied in clinical settings.”
This research was made possible with thanks to generous funding from the National Health and Medical Research Council (NHMRC) and Phenomics Australia.
Read the full publication in Nature Communications.
In 2022, Australian Cancer Research Foundation (ACRF) awarded a grant of $2.1 million to establish the ACRF Centre for Precision Medicine at the Olivia Newton-John Cancer Research Institute (ONJCRI). Here scientists will explore theranostics, a form of precision medicine in which radioisotopes are combined to diagnose and treat a tumour.
Original article source: https://www.onjcri.org.au/latest-news/staff/cas12a-nature-communications/
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