CRISPRa网络中缓解负载的多变量控制：扩展版
Multi-variable control to mitigate loads in CRISPRa networks: Extended Version
AI总结：
针对CRISPRa系统中短RNA引发分子资源负载、导致模块耦合无法独立调控多基因的问题，设计多变量控制器使分子资源浓度对负载变化具鲁棒性，为实际应用的CRISPRa控制器设计奠定基础。
摘要：
CRISPR介导的基因激活（CRISPRa）的发现凭借其可规模化和多路复用的能力，革新了我们开展遗传筛选、生物生产和治疗研究的方式。然而，构成CRISPRa的关键分子资源会因引导这些资源靶向基因的正交短RNA而产生负载，这使得理论上相互独立的CRISPRa模块发生耦合。这种耦合破坏了CRISPRa系统同时独立调控多个基因的能力。本文提出通过缓解构成CRISPRa的分子资源上的负载来减少这种耦合。具体而言，我们设计了一种多变量控制器，使这些分子资源的浓度对短RNA负载水平的变化具有鲁棒性。本研究为设计和实现面向实际应用的CRISPRa控制器奠定了基础。
英文摘要：
The discovery of CRISPR-mediated gene activation (CRISPRa) has transformed the way in which we perform genetic screening, bioproduction and therapeutics through its ability to scale and multiplex. However, the emergence of loads on the key molecular resources constituting CRISPRa by the orthogonal short RNA that guide such resources to gene targets, couple theoretically independent CRISPRa modules. This coupling negates the ability of CRISPRa systems to concurrently regulate multiple genes independent of one another. In this paper, we propose to reduce this coupling by mitigating the loads on the molecular resources that constitute CRISPRa. In particular, we design a multi-variable controller that makes the concentration of these molecular resources robust to variations in the level of the short RNA loads. This work serves as a foundation to design and implement CRISPRa controllers for practical applications.
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