EAGER: Stable iRNA Vectors for Production of Proteins in Pumpkin Sap

该项目致力于满足开发新技术的持续需求，以快速、大规模和具有成本效益的方式生产治疗性肽/蛋白质，如疫苗-现在因COVID-19大流行而变得更加紧迫。利用植物生产生物制品具有速度快、成本低、毒性低等优点，但也存在产量低、纯化过程复杂等缺点。PI将研究一种新的RNA载体，用于研究可能阻碍蛋白质表达的分子稳定性决定因素，并开发南瓜作为宿主，用于生产大量由该RNA载体编码的蛋白质。克服植物疫苗生产的障碍有可能产生更广泛的影响。该项目还为博士后学者提供研究培训和职业发展机会。该研究建立在大量的初步数据基础上，这些数据表明，可以操纵新型病毒样RNA载体（CYVaV）来控制其在宿主植物中的稳定性和相关特性。PI的团队计划修改CYVaV RNA序列和二级结构，目的是优化载体的稳定版本，以便在宿主植物中过表达工程蛋白。开发一种能够感染多种植物的载体平台，用于大规模生产生物制剂，将具有广泛的生物技术和生物医学应用。该项目由分子和细胞生物科学部的遗传机制组资助。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 project tackles the ongoing need to develop new technology for rapid, large-scale and cost-effective production of therapeutic peptides/proteins such as vaccines – now made even more acute by the COVID-19 pandemic. Using plants to produce biological products offers advantages of speed, low cost and low toxicity, but also disadvantages of low yields and complex purification processes. The PI will investigate a novel RNA vector for molecular determinants of stability that can hinder protein expression, and develop pumpkin as a host for producing large amounts of proteins encoded by this RNA vector. Overcoming hurdles to vaccine production in plants has potential for immense broader impact. The project also offers research training and career development opportunities to a post-doctoral scholar.The research builds on substantive preliminary data indicating that a novel virus-like RNA vector (CYVaV) can be manipulated to control its stability and related properties in host plants. The PI’s team plans to modify CYVaV RNA sequence and secondary structure with the goal of optimizing stable versions of the vector for over-expression of engineered proteins in host plants. Development of a vector platform that can serve to infect a variety of plants for large-scale production of biologics will have broad biotechnological and biomedical applications.This project is funded by the Genetic Mechanisms cluster in the Division of Molecular and Cellular Biosciences.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.