Dr Giovanni Pietrogrande and Dr Tahmina Tabassum developed their new fusion protein at UQ's Australian Institute for Bioengineering and Nanotechnology
(Photo credit: The University of Queensland )
A University of Queensland breakthrough could soon be used to upgrade the world's most prominent gene-editing technology to deliver safer and more efficient cancer therapies.
Key points
- CRISPR-Cas9 is a versatile gene editing tool used, among many things, to engineer new cancer immuniotherapies
- While CRISPR is highly efficient and precise, it can sometimes introduce gene mutations to cell products that pose a risk to patients
- UQ researchers have now developed a first-of-its-kind protein that could help CRISPR-Cas9 reduce errors and make it safer to use
Biotechnology researchers have developed a first-of-its-kind protein with the potential to help the widely heralded CRISPR-Cas9 system reduce errors when designing new immunotherapies for lymphoma and leukemia.
Dr Tahmina Tabassum said next-generation cancer therapies were made possible through the gene-editing precision of CRISPR-Cas9.
UQ researchers have developed a first-of-its-kind protein with the potential to improve CRISPR-Cas9 gene editing technology.
(Photo credit: Adobe / Jacqueline weber)
However, she said using the tool sometimes introduced gene mutations to the cell products that posed a risk to patients.
"CRISPR-Cas9 is a highly efficient and precise tool, but it is not perfect," Dr Tabassum said
"When it cuts DNA in the wrong place, you run the risk of introducing genomic instability.
"In ex-vivo therapies such as CAR-T or CAR-NK therapies, this could mean nullifying the effectiveness of the treatment or even activating cancer-causing mutations."
To reduce the error rate when designing such cell therapies, Dr Tabassum and her supervisors Professor Ernst Wolvetang and Dr Giovanni Pietrogrande at UQ's Australian Institute for Bioengineering and Nanotechnology turned to 'fusion proteins' and their potential use as damage regulators for CRISPR-Cas9.
Dr Tabassum said designing and fusing the right protein to the CRISPR-Cas9 enzyme meant it was possible to improve the precision of a DNA cut while stimulating the desired DNA repair.
"There are a lot of great labs that are designing different types of molecules to enhance the gene-editing ability of CRISPR however, most small molecules are either not clinically translatable or focus on improving only the efficiency but not safety," Dr Tabassum said.
"That's why we designed CasPER - a gene-editing technology which is clinically translatable and safer to use."
Designing and fusing the right protein to the CRISPR-Cas9 enzyme makes it possible to improve the precision of a DNA cut while stimulating the desired DNA repair
(Photo credit: Adobe / vchalup)
Paving the way for more efficient cell therapy products
Early testing shows that CasPER can edit genes more effectively than the CRISPR approach in several types of human cells.
Results are particularly promising for advanced immune therapies, such as CAR‑T and CAR‑NK cancer treatments, in which a patient's own immune cells are re-engineered to find and destroy cancer cells.
CasPER's results so far include a precision-editing score nearly 4 times higher than CRISPR-Cas9, as well as 10-fold reduced off-target gene modifications.
"By reducing the overall mutation burden in edited cells, you are laying the groundwork for cell therapy products that are safer and more efficient," Dr Tabassum said.
"Right now, this could mean better CAR therapies for blood cancers.
"But it really opens the door to treatment for a number of diseases caused by genetic factors including rare diseases."
Dr Tahmina Tabassum from UQ's Australian Institute for Bioengineering and Nanotechnology.
(Photo credit: The University of Queensland)
Dr Tabassum said her team was seeking licensing and partnering opportunities to further develop CasPER.
This includes using the technology in combination with other RNA-guided enzymes and or therapies in which genetic material is directly delivered into - or removed from - a patient's body to treat or prevent blood diseases such as sickle cell anemia and thalassemia.
CasPER is currently subject of an Australian provisional patent filed in June 2025 and has the backing of UQ's commercialisation company, UniQuest .
