STTR Phase I: Formulation of a COVID-19 mRNA Vaccine by Inverse Flash NanoPrecipitation

STTR 第一阶段：通过反向闪速纳米沉淀配制 COVID-19 mRNA 疫苗

• 批准号: 2032023
• 负责人: Robert Pagels
• 金额: $ 25.6万
• 依托单位: Optimeos Life Sciences, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2022-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2032023&HistoricalAwards=false
• 关键词: STTR; Phase; Formulation; COVID; 19

The broader impact/commercial potential of this this Small Business Technology Transfer (STTR) Phase I project is the development of a novel messenger ribonucleic acid (mRNA)-based vaccine for COVID-19. The fastest-to-clinic vaccine for COVID-19 was mRNA-based; however, there are no mRNA-based vaccines on the market currently. This is, in part, because this class of vaccines is difficult to optimize and manufacture at a large scale. If clinical trials are successful, hundreds of millions of doses will be needed in the U.S. alone. This STTR project aims to pioneer a novel technique to manufacture mRNA-based vaccines initially for COVID-19. This technology is highly modular, allowing for the better understanding and optimization of this class of vaccines. Importantly, this new technique can be scaled to manufacture the doses needed both for the current COVID-19 pandemic and in the case of future outbreaks. The flexibility and scalability of this platform technology provide a durable competitive advantage. Following demonstration of preclinical efficacy, the company will work with an established pharmaceutical partner for testing and manufacturing. Capturing 5% of the U.S. COVID-19 vaccine market would bring an estimated $125 million in revenue. This is a beachhead market, and, once successful, the company will expand into other mRNA-based vaccine and therapeutic markets.This Small Business Technology Transfer (STTR) Phase I project aims to develop an mRNA-based nanoparticle vaccine for COVID-19 without the use of cationic materials. Current formulation methods require cationic lipids or polymers to form charge-based complexes with the anionic mRNA. Charge-based assembly limits the accessible nanoparticle surface chemistries, a feature crucial to directing which cell types will be transfected and the resulting immune response. Additionally, mRNA is only a minor component of the resulting formulations. The proposed formulation method decouples the mRNA encapsulation from the nanoparticle surface in a two-step process. The method does not require cationic materials, allowing for mRNA loadings up to 5-times higher than those achievable through other routes. However, mRNA transfection has not previously been demonstrated without the use of cationic materials. This will be achieved by completing three key milestones: (1) optimize mRNA encapsulation, (2) vary surface coatings to enhance dendritic cell uptake, and (3) demonstrate efficient cell transfection. A highly loaded nanoparticle formulation that can efficiently target and transfect dendritic cells is desired. Following the completion of this Phase I work, this formulation may be applied to a SARS-CoV-2 spike protein-coding mRNA to produce a COVID-19 vaccine.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业技术转让（STTR）第一阶段项目的更广泛的影响/商业潜力是开发一种新型的基于信使核糖核酸（mRNA）的COVID-19疫苗。最快进入临床的COVID-19疫苗是基于mRNA的;然而，目前市场上没有基于mRNA的疫苗。这在一定程度上是因为这类疫苗难以优化和大规模生产。如果临床试验成功，仅在美国就需要数亿剂。该STTR项目旨在开创一种新技术，以生产最初用于COVID-19的mRNA疫苗。这项技术是高度模块化的，可以更好地理解和优化这类疫苗。重要的是，这种新技术可以扩大规模，以生产当前COVID-19大流行和未来爆发所需的剂量。该平台技术的灵活性和可扩展性提供了持久的竞争优势。在证明临床前疗效后，该公司将与一家成熟的制药合作伙伴合作进行测试和生产。占据美国COVID-19疫苗市场5%的份额将带来约1.25亿美元的收入。这是一个滩头阵地市场，一旦成功，该公司将扩展到其他基于mRNA的疫苗和治疗市场。这个小企业技术转让（STTR）I期项目旨在开发一种基于mRNA的纳米颗粒疫苗，用于COVID-19，而不使用阳离子材料。目前的配制方法需要阳离子脂质或聚合物与阴离子mRNA形成基于电荷的复合物。基于电荷的组装限制了可接近的纳米颗粒表面化学，这是指导哪些细胞类型将被转染和产生免疫应答的关键特征。此外，mRNA仅是所得制剂的次要组分。提出的配制方法通过两步过程将mRNA包裹与纳米颗粒表面分离。该方法不需要阳离子材料，使mRNA载量比通过其他途径实现的mRNA载量高出5倍。然而，mRNA转染以前没有被证明没有使用阳离子材料。这将通过完成三个关键里程碑来实现：（1）优化mRNA包封，（2）改变表面涂层以增强树突状细胞摄取，以及（3）证明有效的细胞转染。需要一种可以有效靶向和抑制树突细胞的高度负载的纳米颗粒制剂。第一阶段工作完成后，该配方可能应用于SARS-CoV-2刺突蛋白编码mRNA，以生产COVID-19疫苗。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。