随着合成基因线路规模的增加,传统的合成基因线路设计思路的瓶颈逐渐凸显,许多之前被忽略的因素对大规模基因线路的性能可能造成显著影响,这对合成基因线路的设计带来了新的挑战。本文重点梳理了基因表达噪声和竞争效应两方面对基因线路性能的影响,阐释了二者间的紧密联系,并基于理性设计的思路,从模拟-数字运算设计、网络拓扑设计、基因线路中的信息传递理论和动态信号等方面,归纳总结了解决这些问题的潜在方案,并展望了规模化合成基因线路理性设计的未来发展方向。
As the scale of synthetic gene circuits grows with sophisticated functions, rational design appears to be a bottleneck to develop synthetic biological systems. In this review, we summarized the impact of gene expression noise and competition effect on the performance of synthetic gene circuits. We also summarized recent progresses on rational design approaches, such as digital-analog circuits, network topologies design, and information-theory-based optimizationapproaches. Finally, we discussed future directions for rational design of synthetic gene circuits.