Improved gene editing tool will deliver safer cancer therapies

An AIBN breakthrough could soon be used to upgrade the world’s most prominent gene-editing technology to deliver safer and more efficient cancer therapies.

Dr Tahmina Tabassum and her supervisors Professor Ernst Wolvetang and Dr Giovanni Pietrogrande 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.

Reducing the error rate

Dr Tabassum said next-generation cancer therapies were made possible through the gene-editing precision of CRISPR-Cas9.

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.”

Safer for the clinic

To reduce the error rate when designing such cell therapies, the team 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.”

Showing promise for immune therapies

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. 

Precision 4x higher than CRISPR-Cas9

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 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.