Triple-negative breast cancer (TNBC), is a special subtype of breast cancer with a poor overall prognosis. Among all breast cancer patients in China, TNBC accounts for about 10-20% of breast cancer. It is more likely to occur in relatively young women, our of its highly invasive and easy to prone to visceral metastasis. The poor prognosis of TNBC is the difficulty in clinical treatment. So gene targeting TNBC is one of the best treatments of choice in the future years.

In this way, we choose to treat TNBC with synthetic biology by the light of nature. In order to treat the TNBC, we design three modules to solve the main two difficulties: specificity and heterogeneity. Our inspiration came from that ‘Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy’. They comprised de novo synthetic cancer-specific promoters and, to enhance specificity, an RNA-based AND gate that generates combinatorial immunomodulatory outputs only when both promoters are mutually active (Figure1). So we are lighted to design the control gene circuit including specific promoter, sponge structure and miR-BS, and finally to trigger the death of the TNBC cells.

In short, the three modules each performs their own functions and integrated tightly: Module1 is used to identify the normal cell and cancer cell; Module2 enhance the specificity of the identical system and also capture the heterogeneous cancer cells. Module3 is a killer to trigger death of the cancer cells which we proposed to design a HIF1αODDD-yCD fusion protein to convert 5-FC to toxic 5-FU [2]. For more information, you guys can go to the following pages!