The study, supported by Phenomics Australia, advances gene editing capabilities for cancer and medical research through unprecedented genetic manipulations using gene-editing enzyme Cas12a.
This story was first published at ONJCRI website.
Australian cancer researchers are the first to establish a next-generation gene-editing tool for modelling and interrogating human disease.
A novel 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 member of the Roche Group.
Cas enzymes are required to cut specific sections of DNA or RNA during CRISPR experiments. CRISPR is a revolutionary gene-editing tool widely used for cancer research, which is currently in the early stages of clinical application in patients.
The researchers were also 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.
Over the past decade, the most widely used Cas enzyme, Cas9, has led to many important discoveries in medical research.
Postdoctoral Researcher at the ONJCRI and WEHI Dr Eddie La Marca, who is a co-lead author on the paper published in Nature Communications today, said:
“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.”
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, Chief Executive Officer of the ONJCRI and Head of the La Trobe University School of Cancer Medicine, 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, including Dr Andrew Kueh, Phenomics Australia Scientific Director, 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.”
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
