Molecular Farming of Recombinant Proteins in Plant Systems

Plant-based molecular farming harnesses the genetic and biochemical machinery of whole plants or plant cells to produce non-native proteins for pharmaceuticals, industrial enzymes and vaccines. Two main expression modalities predominate: stable transformation, where genes are integrated into the nuclear or plastid genome of transgenic plants, and transient expression, which employs agroinfiltration of deconstructed viral vectors to drive rapid, high-level protein accumulation. Key host species include Nicotiana benthamiana, tobacco and various edible crops. Advantages of plant systems encompass low production costs, inherent biosafety due to absence of human pathogens, scalability in field or controlled environments and the capacity for complex eukaryotic post-translational modifications. Glycoengineering and genome-editing approaches have broadened the range of human-type glycan structures achievable in planta, improving the efficacy and safety profile of therapeutic glycoproteins. Plant molecular farming has delivered recombinant antibodies, immune modulators, vaccine antigens and industrial enzymes, with several candidates advancing through clinical or pre-clinical pipelines. Continued innovations in vector design, host optimisation and downstream processing are accelerating the translation of plant-made biologics towards global health and biomanufacturing needs.

Research from Nature Portfolio

Recent studies have demonstrated that combining a geminivirus-derived replication module with dual transcriptional terminators can dramatically enhance transient protein yields in multiple plant species. By integrating a heat-shock protein terminator upstream of an extensin terminator, researchers achieved expression levels of a model fluorescent reporter exceeding 3.7 mg per g fresh weight in Nicotiana benthamiana—approximately double those obtained with single-terminator vectors. This approach proved robust across lettuce, tomato, eggplant and other horticultural hosts, highlighting the versatility of engineered viral replicons for rapid, high-titre production of recombinant proteins in planta.

Molecular Farming of Recombinant Proteins in Plant Systems publication trend

The graph below shows the total number of articles in molecular farming of recombinant proteins in plant systems across all publications each year (not limited to Nature Index journals).

Technical terms

Agroinfiltration: Delivery of genetic constructs into plant tissues by infiltration with Agrobacterium tumefaciens suspensions to achieve transient gene expression.

Transient expression: Short-term production of recombinant proteins in plants without stable genome integration, typically lasting days to weeks.

Geminiviral vector: A deconstructed plant virus-based DNA replicon that amplifies transgene copy number in host cells to enhance expression levels.

Deconstructed viral vector: A modified plant virus genome retaining only essential replication and expression elements, devoid of genes for systemic spread or particle formation.

Glycoengineering: Genetic modification of host glycosylation pathways to produce proteins bearing tailored or human-compatible N-glycan structures.

Fc region: The crystallisable fragment of an antibody that mediates effector functions and influences pharmacokinetics via interactions with cellular receptors and the complement system.

References

1. Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production. Plants (2020).
2. Plant glycoengineering for designing next-generation vaccines and therapeutic proteins. Biotechnology Advances (2023).
3. CRISPR/Cas9‐mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β‐1,2‐xylose and core α‐1,3‐fucose. Plant Biotechnology Journal (2018).
4. Killer to cure: Expression and production costs calculation of tobacco plant‐made cancer‐immune checkpoint inhibitors. Plant Biotechnology Journal (2023).
5. Improving transient protein expression in agroinfiltrated Nicotiana benthamiana. New Phytologist (2024).
6. Improvement of the transient expression system for production of recombinant proteins in plants. Scientific Reports (2018).
7. When plant virology met Agrobacterium: the rise of the deconstructed clones. Plant Biotechnology Journal (2015).