Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Room 5578, Academic Building, Clear Water Bay, Kowloon, Hong Kong.
ACS Synth Biol. 2023 Sep 15;12(9):2516-2523. doi: 10.1021/acssynbio.3c00144. Epub 2023 Aug 31.
Synthetic mRNA circuits manipulate cell fate by controlling output protein expression via cell-specific input molecule detection. Most current circuits either repress or enhance output production upon input binding. Such binary input-output mechanisms restrict the fine-tuning of protein expression to control complex cellular events. Here we designed mRNA circuits using enhancer/repressor modules that were independently controlled by different input molecules, resulting in bidirectional output regulation; the maximal enhancement over maximal repression was 57 fold. The circuit either enhances or represses protein production in different cells based on the difference in the expression of two microRNAs. This study examined novel bidirectional circuit designs capable of fine-tuning protein production by sensing multiple input molecules. It also broadened the scope of cell manipulation by synthetic mRNA circuits, facilitating the development of mRNA circuits for precise cell manipulation and providing cell-based solutions to biomedical problems.
合成 mRNA 电路通过检测细胞特异性输入分子来控制输出蛋白表达，从而改变细胞命运。目前大多数电路要么在输入结合时抑制要么增强输出产物。这种二元输入-输出机制限制了对蛋白质表达的精细调控，以控制复杂的细胞事件。在这里，我们设计了使用增强子/抑制剂模块的 mRNA 电路，这些模块可通过不同的输入分子独立控制，从而实现双向输出调控；最大增强相对于最大抑制的倍数为 57 倍。该电路根据两种 microRNA 表达的差异，在不同细胞中增强或抑制蛋白的产生。本研究探讨了新型的双向电路设计，这些设计能够通过感应多种输入分子来精细调控蛋白质的产生。它还拓宽了合成 mRNA 电路细胞操作的范围，促进了用于精确细胞操作的 mRNA 电路的发展，并为生物医学问题提供了基于细胞的解决方案。
