PFI-TT: Platform Technology for Bioengineering Applications of Large mRNA

这个创新-技术转化伙伴关系（PFI-TT）项目的更广泛的影响/商业潜力将引入一种创新和更有效的选择，以帮助大mRNA进入软骨和关节组织，用于从治疗到研究试剂的各种生物医学应用。随着最近COVID-19疫苗的成功，基于mRNA的疫苗和治疗剂引起了学术界和生物制药行业的极大兴趣。然而，大mRNA的递送仍然是一个重大挑战。所提出的平台技术与传统的运载工具相比具有许多优点。 博士生和本科生将接受技术开发和商业化方面的培训。拟议的项目将开发一种基于创新的DNA启发Janus基础纳米材料（JBN）的大mRNA递送技术，以满足关节和骨骼疾病“难以穿透”软骨组织应用的关键市场需求。大mRNA的递送仍然是一个重大挑战。所提出的平台技术与传统的递送载体如脂质纳米颗粒和聚合物相比具有许多优点。这种新技术具有上级渗透到软骨和其他关节组织中的能力，具有比脂质纳米颗粒显著更好的内体逃逸能力，并且由于其非共价结构和DNA模拟化学，与阳离子聚合物和脂质相比具有显著更低的细胞毒性。此外，这种新的交付技术具有巨大的通用性。根据客户的具体需求，该技术可以针对不同的关节和骨骼疾病进行定制。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 Partnerships for Innovation - Technology Translation (PFI-TT) project will introduce an innovative and more effective option to help large mRNA enter cartilage and joint tissues for a variety of biomedical applications from therapeutics to research reagents. With the recent success of COVID-19 vaccines, mRNA-based vaccines and therapeutics have attracted substantial interest from both academia and the biopharmaceutical industry. However, the delivery of large mRNA is still a major challenge. The proposed platform technology presents many advantages over conventional delivery vehicles. PhD students and undergraduates will receive training in technology development and commercialization. The proposed project will develop a delivery technology based on the innovative DNA-inspired Janus base nanomaterials (JBNs) for large mRNA that addresses a critical market need for applications in “difficult-to-penetrate” cartilage tissue for joint and skeletal diseases. The delivery of large mRNA is still a major challenge. The proposed platform technology presents many advantages over conventional delivery vehicles such as lipid nanoparticles and polymers. This new technology has superior ability to penetrate into cartilage and other joint tissues, has significantly better endosomal escape ability than lipid nanoparticles, and has significant lower cytotoxicity compared to cationic polymers and lipids due to their noncovalent structures and DNA-mimicking chemistry. Furthermore, this new delivery technology has tremendous versatility. Depending on the specific needs of a customer, the technology can be tailored for different joint and skeletal diseases.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.