Next-generation bio-orthogonal reaction platform for RNA tagging and imaging

该后续基金（FoF）提案的总体目标是建立一个新的成像平台来检测基因表达的商业潜力。对于这项概念验证研究，我们将专注于开发新一代RNA成像剂，我们称之为“点击适体酶”。这项工作的基础是小分子的专利发现，这些小分子在生物相关的条件下相互进行选择性化学反应，形成荧光产物。我们现在希望证明当RNA分子在细胞中表达时，增加该反应速率的潜力。如果概念验证实验表明其在细胞环境中是功能性的，则这种RNA成像方法将提供现有成像技术的独特灵敏度优势。为了建立这种新技术的市场途径，关于RNA催化反应的能力以及所需组分的毒性和细胞摄取的基本知识是必不可少的。我们预计，结合技术数据和用户参与活动将简化这些试剂在制药和生物技术领域的商业开发。

The overall objective of this Follow-on-Fund (FoF) proposal is to establish the commercial potential of a new imaging platform to detect gene expression. For this proof of concept study, we will focus on the development of a new generation of RNA imaging agents, which we call 'click-aptazymes'. Underpinning this work is the patented discovery of small molecules which undergo a selective chemical reaction with each other under biologically-relevant conditions to form a fluorescent product. We now wish to demonstrate the potential to increase the rate of this reaction catalyzed by an RNA molecule when expressed in a cell. This RNA imaging approach would provide distinct sensitivity advantages of existing imaging technologies if proof of concept experiments show that it is functional in a cellular environment. In order to establish a route to market for this new technology, fundamental knowledge concerning the ability of RNA to catalyse the reaction, and the toxicity and cell uptake of the requisite components is essential. We envisage that the combined technical data and user engagement activities will streamline the commercial exploitation of these reagents in the pharmaceutical and biotechnology sectors.