Delivering stabilised mRNA to cells for antigen production

将稳定的 mRNA 递送至细胞以产生抗原

• 批准号: 10026414
• 金额: $ 63.62万
• 依托单位: JOHN INNES CENTRE
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10026414
• 关键词: Delivering; stabilised; mRNA; cells; antigen

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.

当前的2019冠状病毒病大流行突出表明，仍然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通过接种疫苗。由于无法事先知道新威胁的性质，因此能够迅速生产和有效分发疫苗以对抗这种威胁至关重要。这就需要发展通用技术，一旦发现新的威胁，就可以迅速部署这些技术来对付它。最近备受关注的一种方法是使用RNA疫苗，这种疫苗旨在产生刺激体内免疫力所需的蛋白质。这种方法的最大优点是，无论RNA分子的来源如何，它们的整体结构都是相似的。因此，使用先前开发的技术可以快速制造新型RNA分子，使该方法具有很高的响应性。这种方法的主要缺点，特别是在世界欠发达地区，是RNA本身不稳定，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。位于英国诺里奇研究园区的约翰英尼斯研究所（JIC）和叶片表达系统（LES）的研究人员已经证明，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的壳可以在大约一周的时间内很容易地在植物中产生，并且可以使用标准程序进行高度纯化。该项目涉及从对低收入和中等收入国家具有重要意义的疾病的生物体中提取这些稳定的rna，以便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rna被细胞吸收的能力，然后在细胞内使用，产生能够刺激免疫反应的蛋白质。通过这种方式，我们打算向世界上冷藏到低温非常困难或不可能的地区提供基于rna的疫苗。因此，该项目将有助于控制世界较贫穷地区的疾病，并将提供对新的疾病威胁迅速作出反应的手段。