Design Considerations of a miRNA Sensor

MiRNAs play important roles in many diseases such as playing a role in promoting immunosuppressive tumour microenvironments (Ren et al., 2019). As such they have been frequently targeted for biomarker discovery (Condrat et al., 2020). In order to accurately incorporate miRNA response into circuits more information is required to understand mode of action of miRNAs upon internalisation and their effect on native and synthetic mRNA targets. To address these issues, we design a chassis for assembly of synthetic mRNA targets containing varying recognition element (MRE) characteristics. This can then be integrated into a workflow for high throughput iteration of MREs. Therefore, varied sensitivity to miRNAs can be easily tuned. To inform the iterations to be assessed for Cholangiocarcinoma detection, we generate a model that sheds light on favourable MRE characteristics such as spacing, multiplicity and complementarity. The model further assesses sensor sensitivity to varying amounts of miRNA and mRNA target and narrows down the parameters to screen for desired miRNA sensor characteristics.

References:

Ren, W., Zhang, X., Li, W., Feng, Q., Feng, H., Tong, Y., Rong, H., Wang, W., Zhang, D., Zhang, Z., Tu, S., Zhu, X. and Zhang, Q., 2019. Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer. Cancer Management and Research, Volume 11, pp.4023-4040.

Condrat, C., Thompson, D., Barbu, M., Bugnar, O., Boboc, A., Cretoiu, D., Suciu, N., Cretoiu, S. and Voinea, S., 2020. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells, 9(2), p.276.