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

这个小企业技术转让（STTR）第一阶段项目的更广泛的影响/商业潜力是克服信使核糖核酸（mRNA）治疗的冷链限制。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中，用于治疗癌症和传染病，基因治疗和细胞治疗。未来十年，mRNA治疗的全球平均收入预计将达到每年约180亿美元。mRNA治疗产品分销的一个主要瓶颈是mRNA药物产品的稳定性差，这导致冷链成本高，浪费大，农村地区的可及性有限。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的低稳定性，并将市场扩大到美国农村和热带国家。这种耐热配方将使美国约6000万农村人口和生活在没有足够冷链设施的热带国家的约30亿人能够获得革命性的mRNA疫苗和药物。该小企业技术转让（STTR）第一阶段项目将提供一种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-LNP）药物产品分销中的冷链挑战。水溶液中的mRNA和mRNA-LNP通过各种途径降解。目前，在不冷冻的情况下增加其稳定性的唯一方法是通过冻干除去水，这需要额外的设施、成本、时间和工艺开发。该STTR I期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用于运输和长期储存的可行性。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20ºC运输两周以上后仍保持90%的活性;（2）为了证明mRNA-LNP药物产品的优化的热稳定制剂保留90%的热稳定性，在热带户外运输过程中，在20ºC下储存6个月以上和50ºC下储存7天后的活性。完成第一阶段项目将提供证据支持专有mRNA和mRNA-LNP配方的热稳定性可以满足工业要求。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。

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.