STTR Phase I: Development of Thermostable Formulations of mRNA Vaccines and Therapeutics

STTR 第一阶段：mRNA 疫苗和治疗药物的耐热配方的开发

• 批准号: 2404627
• 负责人: Harrison Wooten
• 金额: $ 27.5万
• 依托单位: DURAVAX INC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2404627&HistoricalAwards=false
• 关键词: STTR; Phase; Development; Thermostable; Formulations

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to overcome the cold-chain limitation for messenger ribonucleic acid (mRNA) therapy. Besides the COVID-19 mRNA vaccines developed by Moderna and Pfizer, many other mRNA vaccines and drugs are under development for treating cancers and infectious diseases, gene therapy, and cell therapy. The average global revenue of mRNA therapy in the next decade is projected to be ~$18 billion annually. One main bottleneck for the distribution of mRNA therapy products is the poor stability of the mRNA drug products, which results in high cold-chain costs, big wastage, and limited accessibility to rural areas. The thermostable mRNA formulation technology developed in this project will help pharmaceutical companies to save multi-billion dollars per year associated with low stability and expand the market to the rural US and tropical countries. The thermostable formulations will make the revolutionary mRNA vaccines and drugs accessible to the approximately 60 million rural population in the US and the approximately 3 billion people living in tropical countries without adequate cold-chain facilities. Expansion of the market will also lead to more affordable prices of mRNA therapy products for low-income, especially uninsured, families.This Small Business Technology Transfer (STTR) Phase I project will provide a low-cost and scalable solution to eliminate the cold-chain challenges in the distribution of mRNA active pharmaceutical ingredient (API) and mRNA lipid-nanoparticles (mRNA-LNPs) drug products. mRNAs and mRNA-LNPs in aqueous solutions undergo degradation through various pathways. Currently, the only way to increase their stability without freezing is to remove water by lyophilization, which requires additional facility, costs, time, and process development. This STTR Phase I project aims to test the feasibility to store the thermostable liquid formulations of mRNAs and mRNA-LNPs at room temperature for transportation and long-term storage. The research plan is designed towards two objectives: (1) To demonstrate mRNA APIs with various lengths in the optimized granule formulations retain 90% activity after transportation at 20ºC for more than two weeks; (2) To demonstrate that the optimized thermostable formulations of mRNA-LNP drug products retain 90% activity after storage at 20ºC for more than six months and 50ºC for up to 7 days during tropical outdoor transportation. Completing the Phase I project will provide the evidence to support that thermostability of the proprietary mRNA and mRNA-LNP formulations can meet the industrial requirement.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.

该小型企业技术转移（STTR）I期项目的更广泛的影响/商业潜力是克服信使式缎带酸（mRNA）疗法的冷链限制。除了ModernA和辉瑞开发的COVID-19 mRNA疫苗外，许多其他mRNA疫苗和药物正在开发用于治疗癌症和传染病，基因治疗和细胞治疗。未来十年中，mRNA治疗的全球平均收入预计每年约为180亿美元。 mRNA治疗产品分布的一个主要瓶颈是mRNA药物产品的稳定性较差，这会导致高链成本，大废物和对粗糙区域的可及性有限。该项目中开发的热稳定mRNA公式技术将帮助制药公司每年节省数十亿美元与低稳定性相关的数十亿美元，并将市场扩展到美国和热带国家。恒温配方将使美国的大约6000万农村人口以及在没有足够的冷链设施的热带国家中的大约6000万农村人口和大约30亿人口。市场的扩张还将导致低收入（尤其是未保险家庭）的mRNA治疗产品的价格更高。这个小型企业技术转移（STTR）I期项目将提供低成本和可扩展的解决方案，以消除mRNA活性药物成分（API）和mRNA脂质纳米颗粒（mRNA-LNPS）药物的冷链挑战。通过各种途径降解的水溶液中的mRNA和mRNA-LNP。目前，提高稳定性而不冻结的唯一方法是通过冻干去除水，这需要额外的设施，成本，时间和过程开发。该STTR I期项目旨在测试在室温下存储mRNA和mRNA-LNP的热稳定液体配方的可行性，以进行运输和长期存储。该研究计划旨在实现两个目标：（1）证明在优化的颗粒公式中具有不同长度的mRNA API在20ºC下运输后保留90％的活性超过两周； （2）证明MRNA-LNP药物产品的优化热稳定配方在20ºC下在20ºC储存后保持90％的活性超过六个月，在热带户外运输过程中，最多7天，持续7天。完成I期项目将提供证据，以支持专有mRNA和mRNA-LNP公式的热稳定性可以满足工业需求。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的影响审查标准通过评估来获得的支持。