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Cancer fusion genes targeted with CRISPR

8 May 2017
Appeared in BioNews 899

Aggressive human prostate and liver tumours have been shrunk in mice by targeting a 'fused' gene mutation using CRISPR/Cas9.

In a new approach, researchers have used CRISPR-Cas9 genome editing to target fusion genes that promote tumour development. Fusion genes form when two previously separate genes join together and produce an abnormal protein that can lead to cancer, or develop it further.

'This is the first time that genome editing has been used to specifically target cancer fusion genes. It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer,' said Professor Jian-Hua Luo from the University of Pittsburgh School of Medicine, USA, author of the study which was reported in the journal Nature Biotechnology.

The team of researchers had previously identified fusion genes associated with aggressive prostate cancer, including one fusion gene called MAN2A1-FER which is also linked to cancers of the liver, ovaries and lungs.

They developed a CRISPR-Cas9 genome editing tool to target the unique DNA sequences in the MAN2A1-FER gene, and used viruses to deliver it directly to tumour cancer cells in vitro and in mice. The genome editing tool removed the fused gene and replaced it with a gene that could trigger cell death when a drug was administered.

The results of the genome editing killed tumours in vitro, and shrank them in mice. Specifically, genome editing resulted in a 30 per cent reduction in tumour size, no metastasis and none of the mice dying during the eight-week study period. In contrast, the tumours of control mice that received a virus designed to edit a fusion gene that was not present grew by 40 percent, and they all died during the study.

'Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy's soldiers to regroup in the battlefield for a comeback,' said Professor Luo.

It is hoped that Professor Luo's method could be used to target and treat human cancers, which can evolve resistant mutations during standard treatments like chemotherapy. In the future the researchers plan to see if their genome editing technique can eliminate cancer, rather than induce partial remission.

Gene Editing Improves Prostate Cancer Survival, Study in Mice Shows
Prostate Cancer News Today |  2 May 2017
New Gene Therapy Shrinks Aggressive Tumors in Mice
The Scientist |  2 May 2017
Novel gene editing approach to cancer treatment shows promise in mice
Science Daily |  1 May 2017
Targeting genomic rearrangements in tumor cells through Cas9-mediated insertion of a suicide gene
Nature Biotechnology |  1 May 2017
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