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

这一创新-技术转化伙伴关系(PFI-TT)项目的广泛影响/商业潜力将引入一种创新和更有效的选择，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。随着最近新冠肺炎疫苗的成功，基于信使核糖核酸的疫苗和疗法引起了学术界和生物制药行业的浓厚兴趣。然而，大分子信使核糖核酸的传递仍然是一个重大挑战。与传统的运输工具相比，拟议的平台技术具有许多优势。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、以DNA为灵感的Janus碱基纳米材料(JBN)的大信使信使核糖核酸(RNA)的输送技术，以满足关节和骨骼疾病的“难以穿透”的软骨组织应用的关键市场需求。大分子信使核糖核酸的传递仍然是一个重大挑战。与脂类纳米颗粒和聚合物等传统载体相比，拟议的平台技术具有许多优势。这项新技术具有优越的渗透到软骨和其他关节组织的能力，具有比脂质纳米粒更好的内体逃逸能力，并且由于其非共价结构和模拟DNA的化学作用，与阳离子聚合物和脂类相比细胞毒性显著降低。此外，这种新的交付技术具有极大的通用性。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量身定做。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.