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

该项目的目的是在不需要专门设备或技能的情况下，在植物中快速生产抗病毒的口服疫苗。目前的疫苗制造技术需要昂贵的实验室设施和冷链运输系统，导致人们获得疫苗的速度缓慢和不平等。这项研究结合了粒子工程，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疫苗生产的生物制造设备。该项目将通过科学宣传活动和公开视频，提高公众对工程颗粒如何用于将植物转化为生物制造技术的认识。它还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学技术发展的独特机会。一个新的大学水平的工程植物与工程粒子课程将这些植物生物制造的研究成果纳入其课程。与工业界的伙伴关系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础知识和技能，以解决主要的健康，环境和可持续性问题。该项目旨在开发工具，使快速合成和普遍获得的口服mRNA疫苗生产的植物叶绿体原位。利用叶绿体作为无处不在的太阳能分子工厂，通过新兴的基于纳米技术的工具实现个性化的生物制造设备，这是一个尚未开发的潜力。叶绿体是一种生物制造细胞器，具有类似原核生物的基因组、自身的转录和翻译机制，但缺乏基因沉默机制。该系统能够在植物中高表达转基因，以在植物生长的任何地方快速、可调和可扩展地制造mRNA疫苗。尽管生物技术取得了巨大进步，叶绿体基因工程仍然局限于少数植物物种，损害了植物作为广泛使用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，并且需要只有专门的实验室设施才能获得的材料和设备。现有的方法也是破坏性的，效率低下，不能将基因靶向叶绿体。还需要新的技术来方便地封装和回收在非实验室条件下在植物中合成的mRNA疫苗。该研究将研究生物相容性和可降解的高纵横比纳米材料，具有可控的尺寸，可调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疫苗生物制造设备。此外，它将确定叶绿体中的mRNA合成和细胞器双脂质包膜中的封装是否提供了一层保护，使其免受环境中的降解。与工业界的伙伴关系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。来自加州大学滨江，一个少数民族服务机构的学生，将被招募参加该项目。加州大学滨江分校的一门关于植物纳米生物技术的新课程将把这个关于植物生物制造的项目的研究结果纳入其课程。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使用民主化，并彻底改变人类和动物疾病的治疗。这一未来制造奖由化学，生物工程，环境，该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的学术价值和更广泛的影响评审标准。

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.