Synthetic gene circuit selectively kills cancer cells in mouse study

Researchers developed a synthetic gene circuit that selectively triggers cancer-cell death and produced tumour regression in mouse models of colorectal and pancreatic cancer, a Nature study reports. The circuit, called FAST, exploits errors in how cancer cells read genetic instructions when making proteins. Specific pairs of genetic code units cause the protein-making machinery to shift its reading position preferentially in cancer cells. FAST uses that shift to switch on gasdermin D, a protein that triggers inflammatory cell death. Delivery through an AAV9 viral vector also activated immune responses and enhanced effects with immune checkpoint blockade. The proof-of-concept experiments spared normal tissues from detectable toxicity in the tested models.