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Synthetic bacterial vesicles to enhance recombinant protein production, delivery and isolation for Industrial Biotechnology applications.

合成细菌囊泡可增强工业生物技术应用中重组蛋白的生产、递送和分离。

基本信息

批准号：
BB/S005544/1
负责人：
Daniel Mulvihill
金额：
$ 45.87万
依托单位：
University of Kent
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS005544%2F1
关键词：
Synthetic bacterial vesicles enhance recombinant

项目摘要

The ability to reprogram a cell to direct the packaging of specific molecules into discrete membrane envelopes is a major objective for synthetic biology. This controlled packaging into membrane vesicles will allow biologists to create a plethora of new technologies, which could be applied in both biotechnology and medical industries. These include the generation of novel metabolic factories within a cell for energy production; for rapidly packaging toxic proteins into contained environments before they have a chance to harm any normal metabolic activities, so they can be purified for use in subsequent pharmaceutical applications; the creation of protective packages filled with difficult to isolate biomolecules, which can be kept in stable environment to allow their storage and purification; and also generate simple vehicles for delivery of drugs and vaccines to the patient.Here, we provide a simple and cost effective solution to the problem. We have discovered a method to program a simple cell to create membrane packages which can be filled with different molecules of interest. We have not only discovered a way to fine-tune the shape of the membrane package (e.g. into long tubular matrices or spherical vesicles), but we have also devised controllable mechanisms that either keep the package within, or secrete the package out of the cell. Thus we have therefore made a landmark breakthrough in synthetic biology research. A major aim of this BBSRC key strategic area is to design from new and improve on natural systems and exploit these for the production of commercially important chemicals and biotherapeutics, which is what we have achieved here.Our overall aim in this project is to make use of these exciting discoveries to modify cells, making them capable of creating membrane bound packages filled with any protein of interest, which can then either be secreted from the cell and isolated from the culture media using a simple one step filtration technique, or stored within the cell where it can be made to act as a metabolic micro-factories, producing useful and/or valuable molecules without intoxicating the cells. In this way we hope to develop new ways to produce fine and platform chemicals as well as biotherapeutics.Through the research described in this application we are certain that we will be able to contribute to the development of new sustainable approaches for generating biotherapeutics, which will be assimilated into production techniques by diverse bio-industries.

对细胞进行重编程以将特定分子包装到离散的膜包膜中的能力是合成生物学的主要目标。这种受控包装成膜囊泡将使生物学家能够创造出大量新技术，这些技术可以应用于生物技术和医疗行业。这些包括在细胞内产生新的代谢工厂以产生能量;在有毒蛋白质有机会损害任何正常代谢活动之前将其快速包装到封闭的环境中，因此它们可以被纯化以用于随后的药物应用;创建填充有难以分离的生物分子的保护性包装，其可以保持在稳定的环境中以允许其储存和纯化;并产生简单的车辆，用于向患者输送药物和疫苗。在这里，我们提供了一个简单且具有成本效益的解决方案。我们已经发现了一种方法，可以对一个简单的细胞进行编程，以创建可以填充不同感兴趣分子的膜包。我们不仅发现了一种微调膜包装形状的方法（例如，将其调整为长管状基质或球形囊泡），而且我们还设计了可控机制，可以将包装保持在细胞内，也可以将包装分泌出细胞。因此，我们在合成生物学研究方面取得了里程碑式的突破。该BBSRC关键战略领域的一个主要目标是从新设计和改进自然系统，并利用这些系统生产具有商业重要性的化学品和生物治疗药物，这就是我们在这里所实现的。我们在这个项目中的总体目标是利用这些令人兴奋的发现来修饰细胞，使它们能够创造充满任何感兴趣的蛋白质的膜结合包，其然后可以从细胞中分泌并使用简单的一步过滤技术从培养基中分离，或者储存在细胞内，在细胞内可以使其充当代谢微工厂，产生有用和/或有价值的分子而不使细胞中毒。通过这种方式，我们希望开发新的方法来生产精细和平台化学品以及生物治疗剂。通过本申请中描述的研究，我们确信我们将能够为开发生物治疗剂的新的可持续方法做出贡献，这些方法将被各种生物工业吸收到生产技术中。