Delivering stabilised mRNA to cells for antigen production

当前的新冠肺炎大流行突显了继续需要保护民众免受新出现的疾病威胁。实现这一目标的最有效方法之一是接种疫苗。由于事先不知道新威胁的性质，因此能够快速生产和有效分发疫苗来对抗它是至关重要的。这需要开发通用技术，一旦发现新的威胁，就可以迅速部署这些技术来对付新的威胁。最近出现的一种方法是使用RNA疫苗，这种疫苗旨在产生刺激体内免疫所需的蛋白质。这种方法的最大优点是，无论其来源如何，RNA分子都具有相似的整体结构。因此，可以使用先前开发的技术快速制造新型RNA分子，使方法具有高度响应性。这种方法的主要缺点是，特别是在世界欠发达地区，RNA天生不稳定，基于它的疫苗必须在低温下储存和分发。因此，有必要开发在部署之前稳定RNA分子的方法。总部设在英国诺维奇研究公园的约翰·英尼斯研究所(JIC)和叶表达系统(LES)的研究人员已经表明，用植物病毒的外壳蛋白外壳包围RNA可以极大地稳定它们。这种含有所需RNA的壳可以在植物中轻松地在大约一周内生产出来，并且可以使用标准程序进行高度纯化。该项目涉及将这些稳定的RNA从引起对低收入和中等收入国家重要疾病的生物体中分离出来，以便能够在不需要冷藏的情况下广泛分发。因此，我们将与英国利兹大学(UOL)合作，测试受保护的RNA被细胞吸收，然后在细胞内用于产生能够刺激免疫反应的蛋白质的能力。通过这种方式，我们打算将基于RNA的疫苗提供给世界上那些很难或不可能进行低温制冷的地区。因此，该项目将为世界较贫穷地区的疾病控制作出贡献，并将提供快速应对新的疾病威胁的手段。

The current Covid-19 pandemic has highlighted the continuing need to protect populations from emerging disease threats. One of the most efficient ways of achieving this is through vaccination. Since the nature of a new threat is not known in advance, it is critical that vaccines can be produced quickly and distributed efficiently to combat it. This requires the development of generic technologies which can be rapidly deployed to combat a new threat as soon as it has been identified. One method that has come to prominence recently is the use of RNA vaccines which are designed to produce the proteins necessary to stimulate immunity within the body. The great advantage of this approach is that RNA molecules have a similar overall structure regardless of their origin. Thus, new types of RNA molecules can be rapidly made using previously developed technology making the approach highly responsive. The major drawback of the approach, particularly in less developed regions of the world, is that RNA is inherently unstable, and vaccines based on it have to be stored and distributed a low temperature. Thus, there is a need to develop methods for stabilising RNA molecules prior to deployment.Researchers at the John Innes Institute (JIC) and Leaf Expression Systems (LES), both based on Norwich Research Park, UK, has shown that surrounding RNAs with the coat protein shell of a plant virus greatly stabilises them. Such shells containing the required RNA can be produced easily in plants in about one week and they can be highly purified using standard procedures. The project involves basing these stabilised RNAs from organisms that cause diseases of importance to low- and middle-income countries so that can be widely distributed without the need for refrigeration. In collaboration with the University of Leeds (UoL), UK, We will therefore test the ability of the protected RNAs to be taken up by cells and then used within the cells to produce proteins that are able to stimulate an immune response. In this way, we intend to make RNA-based vaccines available to regions of the world where refrigeration to low temperatures is either very difficult or impossible. Thus, the project will make a contribution to the control of diseases in poorer regions of the world and will provide means of rapidly responding to new disease threats.