FMSG: Bio: Rapid Biomanufacturing of mRNA Vaccines in Plant Chloroplasts

这个项目的目的是在不需要专门设备或技能的情况下，在植物中快速生产针对病毒的口服疫苗。目前的疫苗制造技术需要昂贵的实验室设施和冷链输送系统，这导致人们获得疫苗的速度缓慢且不平等。这项研究结合了颗粒工程、叶绿体遗传学和植物分子农业的思想和方法，将菠菜或生菜等可食用植物叶片的叶绿体转化为用于疫苗生产的生物制造设备。该项目将通过科学推广活动和公开视频，提高公众对如何利用工程颗粒将植物转化为生物制造技术的认识。它也将为博士后研究人员和学生提供超越学科背景和实践团队科技发展的独特机会。一门新的大学水平的工程植物与工程颗粒课程将把这些植物生物制造的发现纳入其课程。与工业界的合作将为植物生物制造技术的设计、适用性和成本效益提供信息，并为学生和博士后提供宝贵的网络和教育机会。植物生物制造混合会议将促进学术界和工业界关键利益相关者的整合。总之，这些方法将培养未来的生物制造劳动力准备开发和应用基本知识和技能，以解决重大的健康，环境和可持续发展问题。该项目旨在开发工具，使植物叶绿体原位生产的口服mRNA疫苗能够快速合成和普遍获得。利用叶绿体作为无处不在的太阳能分子工厂，利用新兴的基于纳米技术的工具实现个性化生物制造设备，这是一个尚未开发的潜力。叶绿体是生物制造细胞器，具有类似原核生物的基因组，有自己的转录和翻译机制，但缺乏基因沉默机制。该系统能够在植物中实现转基因的高表达，以便在植物生长的任何地方快速、可调和可扩展地生产mRNA疫苗。尽管生物技术取得了巨大的进步，但叶绿体基因工程仍然局限于少数植物物种，阻碍了植物作为广泛可获得的生物制造设备的使用。将重组DNA引入植物叶绿体的主要方法是昂贵的，并且需要只有专门实验室设施才能获得的材料和设备。现有的方法也具有破坏性，效率低下，并且无法将基因靶向到叶绿体中。在非实验室条件下对植物合成的mRNA疫苗进行快速封装和提取也需要新的技术。该研究将研究生物相容性和可降解的高纵横比纳米材料，这些材料具有可控的尺寸，可调节的表面电荷和化学性质，作为质粒DNA递送载体，将可食用植物转化为mRNA疫苗生物制造装置。在正交方面，它将确定叶绿体中的mRNA合成和细胞器双脂质包膜中的包封是否提供了一层防止环境降解的保护。与工业界的合作将为植物生物制造技术的设计、适用性和成本效益提供信息，并为学生和博士后提供宝贵的网络和教育机会。加州大学河滨分校是一所为少数族裔服务的机构，该校将招募学生参与该项目。加州大学河滨分校开设了一门关于植物纳米生物技术的新课程，将把该项目在植物生物制造方面的发现纳入课程。基于纳米生物技术的方法有可能使植物叶绿体用于个性化生物分子制造的大众化，并彻底改变人类和动物疾病的治疗。该未来制造奖由化学、生物工程、环境和运输系统部门以及化学部门支持。该奖项反映了美国国家科学基金会的法定使命，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。

This project aims to enable rapid manufacturing of oral vaccines against viruses in plants without the need of specialized equipment or skills. Current vaccine manufacturing technologies need expensive laboratory facilities and cold-chain delivery systems that result in slow and unequal access of vaccines to people. This study combines ideas and approaches from the engineering of particles, chloroplast genetics, and plant molecular farming, to turn chloroplasts of edible plant leaves like spinach or lettuce into biomanufacturing devices for vaccine production. The project will increase public awareness of how engineered particles can be used to turn plants into a biomanufacturing technology through science outreach events and publicly available videos. It will also provide unique opportunities for postdoctoral researchers and students to grow beyond their disciplinary background and practice team science and technology development. A new college level course on engineering plants with engineered particles will incorporate these plant biomanufacturing findings into its curriculum. Partnerships with industry will inform the design, applicability, and cost-effectiveness of plant biomanufacturing technologies, and provide valuable networking and education opportunities for students and postdocs. Plant biomanufacturing hybrid meetings will promote integration of key stakeholders from academia and industry. Together, these approaches will train a future biomanufacturing workforce prepared to develop and apply fundamental knowledge and skills to solve major health, environmental, and sustainability problems.This project aims to develop tools that allow rapid synthesis and universal access of oral mRNA vaccines manufactured in situ by plant chloroplasts. There is an untapped potential for utilizing chloroplasts as ubiquitous solar powered molecular factories for personalized biomanufacturing devices enabled by emergent nanotechnology-based tools. Chloroplasts are biomanufacturing organelles with a prokaryotic-like genome, their own transcription and translation machinery, but lack gene silencing mechanisms. This system enables high expression of transgenes in plants for rapid, tunable, and scalable manufacturing of mRNA vaccines anywhere plants grow. Despite great strides made in biotechnology, chloroplast genetic engineering remains limited to a few plant species, impairing the use of plants as widely accessible biomanufacturing devices. The main method for the introduction of recombinant DNA to chloroplasts in plants is costly, and requires materials and equipment that are only accessible to specialized lab facilities. Existing methods are also destructive, inefficient, and unable to target genes into chloroplasts. Novel technologies are also needed for facile encapsulation and retrieval of mRNA vaccines synthesized in plants in non-laboratory conditions. The study will investigate biocompatible and degradable high aspect ratio nanomaterials with controllable dimensions, tunable surface charge and chemistry as plasmid DNA delivery vehicles for turning edible plants into mRNA vaccine biomanufacturing devices. Orthogonally, it will determine if mRNA synthesis in chloroplasts and encapsulation in the organelle double lipid envelopes provide a layer of protection from degradation in the environment. Partnerships with industry will inform the design, applicability, and cost-effectiveness of plant biomanufacturing technologies, and provide valuable networking and education opportunities for students and postdocs. Students from UC Riverside, a minority-serving institution, will be recruited to participate in the project. A new course on plant nanobiotechnology at UC Riverside will incorporate the findings of this project on plant biomanufacturing into its curriculum. Nanobiotechnology-based approaches have the potential to democratize the use of plant chloroplasts for personalized biomolecule manufacturing and revolutionize the treatment of human and animal disease.This Future Manufacturing award is supported by the Division of Chemical, Bioengineering, Environmental, and Transport Systems and the Division of Chemistry.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.