CRISPR targets key cancer gene in Ewing sarcoma

Ewing sarcoma is an aggressive paediatric cancer that primarily affects the bones and soft tissues. It is characterised by chromosomal translocations that produce oncogenic fusion proteins, most commonly EWSR1::FLI1, which drive tumour growth by altering gene expression.

The researchers targeted EWSR1::FLI1 using CRISPR-Cas9 under the control of a GGAA repeat-based promoter (GGAAprom), which is selectively activated by the fusion protein. This approach ensured that Cas9 was only expressed in Ewing sarcoma cells, minimising off-target effects.

In vitro, GGAAprom-driven Cas9 effectively disrupted EWSR1::FLI1 and halted cell proliferation. In vivo, adenoviral delivery of this system significantly reduced tumour growth in mice without affecting normal tissues. The findings highlight the potential of a tumour-specific CRISPR therapy for Ewing sarcoma.

The research was led by Saint T. Cervera and Javier Alonso at the Instituto de Salud Carlos III in Madrid, Spain. It was published in Cancer Gene Therapy on 15 March 2025.