BODIPY Photocage-Enabled Visualization and Optical Control of saRNA Delivery and Immunogenicity

BODIPY Photocage 实现 saRNA 传递和免疫原性的可视化和光学控制

• 批准号: EP/X027252/1
• 负责人: Molly Stevens
• 金额: $ 24.26万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX027252%2F1
• 关键词: BODIPY; Photocage; Enabled; Visualization; Optical

RNA-based vaccines because of their enhanced immune response and cell-free manufacturing have become a potent and economical alternative to conventional vaccination approaches during the ongoing SARS-CoV-2 pandemic. The intrinsic single-stranded nature of RNA, however, oftentimes results in chemical instability and thus attenuated efficiency. One way to circumvent this issue is to use advanced delivery strategies which can stabilize RNA structures as well as allow efficient in vivo delivery and release. The objective of this proposal is to develop a light-responsive and fluorescent self-reporting RNA delivery system through integrating NIR light activated BODIPY photocages (Bpc) into RNA-loaded cationic polymers. In the current design, Bpc function both as the emissive self-reporters and photosensitive units. The Bpc emission will allow for real-time monitoring of the nanocarrier distribution and the photocaging process will enable on-demand release of the loaded RNA using light. To further explore this delivery platform, I will also investigate the delivery and controlled release properties of the nitro-functionalized Bpc (BpcNO2), the light-dependent fluorescence change of which can serve as an internal indicator to quantify the amount of released RNA. The success of the proposed work will offer 1) a novel, straightforward and biocompatible strategy to construct NIR light responsive and fluorescence traceable RNA delivery systems which are capable of maintaining the structural integrity and ensuring the translational efficiency of RNAs and 2) a chemical biology tool to probe the in vivo distribution and modulate the dose of immunogenic RNAs.

在SARS-CoV-2大流行期间，基于RNA的疫苗由于其增强的免疫反应和无细胞制造，已成为传统疫苗接种方法的有效和经济的替代方案。然而，RNA固有的单链性质往往会导致化学不稳定，从而降低效率。规避这个问题的一种方法是使用先进的递送策略，这种策略可以稳定RNA结构，并允许有效的体内递送和释放。该方案的目的是通过将近红外光活化的BODIPY光笼(BPC)整合到RNA负载的阳离子聚合物中，开发一种光响应和荧光自报告的RNA递送系统。在目前的设计中，BPC既起到发射自报告器的作用，又起到感光单元的作用。原料药的发射将允许实时监测纳米载体的分布，而光笼化过程将使所加载的RNA能够使用光按需释放。为了进一步探索这个递送平台，我还将研究硝基功能化的BPC(BpcNO2)的递送和控制释放特性，其光依赖的荧光变化可以作为量化RNA释放量的内部指标。这项工作的成功将提供1)一种新的、直接的和生物相容的策略来构建近红外光响应和荧光可追踪的RNA递送系统，该系统能够保持RNA的结构完整性和确保翻译效率；2)一种化学生物学工具来探测免疫原性RNA的体内分布和调节剂量。