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

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.