SynBioCentre, University College Cork, Cork, Ireland; Cork Cancer Research Centre, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
Cork Cancer Research Centre, University College Cork, Cork, Ireland.
J Control Release. 2018 Apr 10;275:217-228. doi: 10.1016/j.jconrel.2018.02.023. Epub 2018 Feb 22.
The ability to modify existing microbiota at different sites presents enormous potential for local or indirect management of various diseases. Because bacteria can be maintained for lengthy periods in various regions of the body, they represent a platform with enormous potential for targeted production of biomolecules, which offer tremendous promise for therapeutic and diagnostic approaches for various diseases. While biological medicines are currently limited in the clinic to patient administration of exogenously produced biomolecules from engineered cells, in situ production of biomolecules presents enormous scope in medicine and beyond. The slow pace and high expense of traditional research approaches has particularly hampered the development of biological medicines. It may be argued that bacterial-based medicine has been "waiting" for the advent of enabling technology. We propose that this technology is Synthetic Biology, and that the wait is over. Synthetic Biology facilitates a systematic approach to programming living entities and/or their products, using an approach to Research and Development (R&D) that facilitates rapid, cheap, accessible, yet sophisticated product development. Full engagement with the Synthetic Biology approach to R&D can unlock the potential for bacteria as medicines for cancer and other indications. In this review, we describe how by employing Synthetic Biology, designer bugs can be used as drugs, drug-production factories or diagnostic devices, using oncology as an exemplar for the concept of in situ biomolecule production in medicine.
在不同部位修饰现有微生物群落的能力为局部或间接管理各种疾病提供了巨大的潜力。由于细菌可以在身体的各个部位长期存在，因此它们代表了一个具有巨大潜力的平台，可以靶向生产生物分子，为各种疾病的治疗和诊断方法提供巨大的希望。虽然生物药物目前在临床上仅限于患者从工程细胞中外源性施用外源性生物分子，但生物分子的原位生产在医学及其他领域具有巨大的应用前景。传统研究方法的缓慢步伐和高昂成本特别阻碍了生物药物的发展。有人可能会说，基于细菌的药物一直在等待能够实现这一目标的技术的出现。我们认为，这项技术就是合成生物学，而等待已经结束。合成生物学为对生物体及其产物进行编程提供了一种系统的方法，采用了一种研究与开发（R&D）方法，使产品的开发变得快速、廉价、易于获取，同时又十分复杂。充分利用合成生物学的研发方法，可以挖掘细菌在癌症和其他适应症方面作为药物的潜力。在这篇综述中，我们描述了如何通过采用合成生物学，将设计好的细菌用作药物、药物生产工厂或诊断设备，以肿瘤学为例，说明了在医学中进行生物分子原位生产的概念。
