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.

该小企业技术转让 (STTR) 第一阶段项目的更广泛影响/商业潜力是克服信使核糖核酸 (mRNA) 疗法的冷链限制，除了 Moderna 和辉瑞开发的 COVID-19 mRNA 疫苗外，还有许多其他疫苗。 mRNA 疫苗和药物正在开发中，用于治疗癌症和传染病、基因疗法和细胞疗法。预计未来十年 mRNA 疗法的全球平均收入约为每年 180 亿美元。这是 mRNA 疗法分销的一个主要瓶颈。产品是mRNA药物产品稳定性差，导致冷链成本高、浪费大、农村地区可及性有限。该项目开发的耐热mRNA制剂技术将帮助制药公司每年节省数十亿美元。稳定性低，并将市场扩大到美国农村和热带国家，该耐热配方将使美国约 6000 万农村人口和生活在没有足够寒冷的热带国家的约 30 亿人能够获得革命性的 mRNA 疫苗和药物。连锁设施的扩张。该市场还将为低收入家庭，特别是没有保险的家庭带来更实惠的 mRNA 治疗产品价格。这个小型企业技术转让 (STTR) 第一阶段项目将提供低成本且可扩展的解决方案，以消除冷链挑战mRNA 活性药物成分 (API) 和 mRNA 脂质纳米颗粒 (mRNA-LNP) 药品在水溶液中通过各种途径发生降解，目前，在不冷冻的情况下提高其稳定性的唯一方法是。删除STTR 第一阶段项目旨在测试在室温下储存 mRNA 和 mRNA-LNP 的热稳定液体制剂以进行运输和长期储存的可行性。该研究计划旨在实现两个目标：(1) 证明优化颗粒制剂中不同长度的 mRNA API 在 20°C 运输两周以上后仍保留 90% 的活性； mRNA-LNP 药物产品的热稳定配方在热带户外运输过程中在 20°C 下储存超过六个月和在 50°C 下储存长达 7 天后仍保留 90% 的活性。完成第一阶段项目将为支持专有 mRNA 的热稳定性提供证据。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，认为值得支持。