Australian scientists have sharpened a valuable tool in cancer research.

A local team has developed a pre-clinical model featuring an enhanced version of the Cas12a enzyme, a next-generation genome-engineering tool.

Cas enzymes are critical components in CRISPR gene-editing systems, which allow researchers to cut and modify specific sections of DNA. 

While Cas9 has been the dominant enzyme in medical research for over a decade, a new study, published in Nature Communications, marks the first time Cas12a has been effectively used in pre-clinical models.

The breakthrough was made by scientists from the Olivia Newton-John Cancer Research Institute (ONJCRI), La Trobe University, and the Walter and Eliza Hall Institute of Medical Research (WEHI), in collaboration with Genentech.

“This is the first time Cas12a has been used in pre-clinical models, which will greatly advance our genome engineering capabilities,” said Dr Eddie La Marca, postdoctoral researcher at ONJCRI and WEHI. 

“In contrast to Cas9, Cas12a can delete multiple genes at the same time with extremely high efficiency.”

The researchers used Cas12a to find specific genes that speed up lymphoma growth in mice.

This multiplexed gene-editing approach enables simultaneous deletion and activation of different genes, offering new ways to model and investigate complex genetic disorders.

Co-lead authors Ms Wei Jin and Dr Yexuan Deng from ONJCRI and WEHI highlighted the potential of this new tool.

“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 model and interrogate complex genetic disorders,” they said. 

Beyond advancing fundamental cancer research, the team is focusing on developing CRISPR-based therapies for clinical use. 

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