Loading and release of RNA for COVID-19 vaccines: direct visualization of lipid nanoparticle delivery vehicles.

COVID-19 疫苗 RNA 的加载和释放：脂质纳米颗粒递送载体的直接可视化。

• 批准号: 554165-2020
• 负责人: Leslie, Sabrina
• 金额: $ 3.64万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=704906
• 关键词: Loading; release; RNA; COVID; 19

The coronavirus pandemic has created an immediate need for Covid-19 vaccines and therapies. Several companies have developed vaccines which are already in clinical trials, where lipid nanoparticles (LNPs) are used to deliver RNA to target cells in humans. Here they stimulate the production of a single viral protein which elicits an immune response. RNA-based vaccines are potentially safer, cheaper, and lower dose than other vaccines, and can be manufactured fast enough to respond to the kind of global pandemic in which we find ourselves today. This is a completely new vaccine technology and there is much to learn and optimize about its mode of action. Our proposal aims to visualize the interactions of RNA with LNP delivery vehicles, characterizing the structure and RNA-carrying capacity of LNPs, in order to better understand and control the delivery of these therapeutic compounds to targeted cells in the body. Precision Nanosystems Inc (PNI) has developed the LNP delivery platform technology used by pharmaceutical companies in their development of vaccines and other Covid-19 therapeutics. The Leslie Lab at McGill University has developed a novel single-particle imaging technique called Convex Lens-induced Confinement ("CLiC"), which enables direct imaging of individual nanoparticles and molecules as they interact in solution. Our collaboration combines two made-in-Canada technologies to accelerate the development of Covid-19 vaccines. Using CLiC microscopy to study PNI's nanoparticle delivery technology, we can make new discoveries about the structure of LNPs, how they interact with RNA cargo, and how they deliver RNA to cells. CLiC can yield more detailed information than current techniques can provide, so we will gain insights into LNP behavior that were previously unattainable. Our research will create new tools and allow vaccine developers to design and optimize RNA-based therapeutics more efficiently, bringing much needed therapies more quickly to market.

新型冠状病毒大流行造成了对新型冠状病毒疫苗和疗法的迫切需求。 几家公司已经开发出已经在临床试验中的疫苗，其中脂质纳米颗粒（LNP）用于将RNA递送到人体的靶细胞。 在这里，它们刺激产生一种单一的病毒蛋白，从而引发免疫反应。 基于RNA的疫苗可能比其他疫苗更安全，更便宜，剂量更低，并且可以快速生产，以应对我们今天发现的全球流行病。 这是一种全新的疫苗技术，关于其作用模式有很多需要学习和优化的地方。 我们的提案旨在可视化RNA与LNP递送载体的相互作用，表征LNP的结构和RNA携带能力，以便更好地理解和控制这些治疗化合物向体内靶细胞的递送。 Precision Nanosystems Inc（PNI）开发了LNP输送平台技术，制药公司在开发疫苗和其他Covid-19治疗药物时使用该技术。麦吉尔大学的莱斯利实验室开发了一种新的单粒子成像技术，称为凸透镜诱导约束（“CLiC”），它可以直接成像单个纳米粒子和分子，因为它们在溶液中相互作用。我们的合作结合了两种加拿大制造的技术，以加快新型冠状病毒疫苗的开发。 使用CLiC显微镜来研究PNI的纳米颗粒递送技术，我们可以对LNP的结构、它们如何与RNA货物相互作用以及它们如何将RNA递送到细胞中做出新的发现。 CLiC可以产生比现有技术更详细的信息，因此我们将获得以前无法实现的LNP行为的见解。 我们的研究将创造新的工具，使疫苗开发人员能够更有效地设计和优化基于RNA的疗法，从而更快地将急需的疗法推向市场。