Bello Adebayo J, Popoola Abdulgafar, Okpuzor Joy, Ihekwaba-Ndibe Adaoha E, Olorunniji Femi J
School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
Department of Biological Sciences, Redeemer's University, Ede 232101, Osun State, Nigeria.
Bioengineering (Basel). 2023 Dec 25;11(1):22. doi: 10.3390/bioengineering11010022.
Advances in synthetic biology have led to the design of biological parts that can be assembled in different ways to perform specific functions. For example, genetic circuits can be designed to execute specific therapeutic functions, including gene therapy or targeted detection and the destruction of invading viruses. Viral infections are difficult to manage through drug treatment. Due to their high mutation rates and their ability to hijack the host's ribosomes to make viral proteins, very few therapeutic options are available. One approach to addressing this problem is to disrupt the process of converting viral RNA into proteins, thereby disrupting the mechanism for assembling new viral particles that could infect other cells. This can be done by ensuring precise control over the abundance of viral RNA (vRNA) inside host cells by designing biological circuits to target vRNA for degradation. RNA-binding proteins (RBPs) have become important biological devices in regulating RNA processing. Incorporating naturally upregulated RBPs into a gene circuit could be advantageous because such a circuit could mimic the natural pathway for RNA degradation. This review highlights the process of viral RNA degradation and different approaches to designing genetic circuits. We also provide a customizable template for designing genetic circuits that utilize RBPs as transcription activators for viral RNA degradation, with the overall goal of taking advantage of the natural functions of RBPs in host cells to activate targeted viral RNA degradation.
合成生物学的进展促使人们设计出能够以不同方式组装以执行特定功能的生物部件。例如，可以设计基因回路来执行特定的治疗功能，包括基因治疗或靶向检测以及破坏入侵病毒。病毒感染很难通过药物治疗来控制。由于它们的高突变率以及它们劫持宿主核糖体来制造病毒蛋白的能力，可用的治疗选择非常少。解决这个问题的一种方法是破坏将病毒RNA转化为蛋白质的过程，从而破坏组装可能感染其他细胞的新病毒颗粒的机制。这可以通过设计生物回路靶向vRNA进行降解来确保对宿主细胞内病毒RNA（vRNA）丰度的精确控制来实现。RNA结合蛋白（RBP）已成为调节RNA加工的重要生物装置。将天然上调的RBP纳入基因回路可能具有优势，因为这样的回路可以模拟RNA降解的天然途径。本综述重点介绍了病毒RNA降解过程以及设计基因回路的不同方法。我们还提供了一个可定制的模板，用于设计利用RBP作为病毒RNA降解转录激活因子的基因回路，其总体目标是利用宿主细胞中RBP的天然功能来激活靶向病毒RNA降解。
