Australian team develops novel gene-editing technology with oncology applications

Study advances gene-editing capabilities for cancer and medical research through genetic manipulations using Cas12a enzyme

Australian cancer researchers have been the first to establish a novel gene-editing tool for modelling and interrogating human disease.

A pre-clinical model expressing an enhanced version of a new genome-engineering enzyme called Cas12a was generated by researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI), WEHI and Genentech, a Roche Group company.

Cas enzymes are used to cut up specific sections of DNA or RNA during CRISPR experiments which is a gene-editing tool used for oncology research and has recently started to deliver clinical applications to patients, with Casgevy being the first CRISPR-Cas9 therapy to receive approval by the MHRA, FDA and EMA at the end of 2023.

Over the past decade, the most widely used Cas enzyme, Cas9, has led to many important discoveries in medical research.

In this research the team were able to identify genes that led to accelerated lymphoma growth in the pre-clinical model by using unique Cas12a-compatible mouse whole-genome CRISPR ‘libraries’.

This new research contributes to a better understanding of the limitations of CRISPR technology, with the ultimate goal of making it a viable option for cancer treatment in patients.

“This is the first time Cas12a has been used in pre-clinical models, which will greatly advance our genome engineering capabilities. In contrast to Cas9, Cas12a can delete multiple genes at the same time with extremely high efficiency,” said Dr Eddie La Marca, postdoctoral researcher at the ONJCRI and WEHI. Dr La Marca is a co-lead author on the paper.

The researchers also used Cas12a in combination with other genome engineering tools, allowing for ‘multiplexed’ gene manipulation. Co-lead authors Ms Wei Jin and Dr Yexuan Deng (ONJCRI and WEHI) elaborated on this:

“We have also crossed our Cas12a animal model with a model that expresses an altered version of Cas9, allowing us to both delete and activate different genes simultaneously. This will allow researchers to use this tool to model and interrogate complex genetic disorders."

Professor Marco Herold, Head of the La Trobe University School of Cancer Medicine and CEO of ONJCRI, said:

“We are certain that this work will encourage other research teams to use this Cas12a pre-clinical model which, in combination with the screening libraries, are a powerful new suite of gene-editing tools to improve our understanding of the mechanisms behind many different cancers.”

Professor Herold’s team at the ONJCRI are also focusing their efforts on developing methods to administer CRISPR-based therapies to patients, highlighting the growing importance of gene-editing tools such as Cas12a.

Professor Herold said: “This Cas12a pre-clinical model will also be instrumental to advancing our understanding of how CRISPR tools could be translated to clinical usage.”

For further reading please visit: 10.1038/s41467-025-56282-2