Innovation in plant-based transient protein expression for infectious disease prevention and preparedness

Addressing new challenges in global health and biosecurity requires responsive and accessible platforms for the manufacture of preventative or therapeutic interventions. Transient protein expression in plants has evolved into a technology that offers a unique combination of rapid expression, inherent scalability, and flexibility in gene stacking with the capability to produce complex proteins and protein assemblies. Technical developments that have driven the progress of transient expression in plants include advanced expression systems, protein engineering and synthetic biology approaches to transiently, or stably, modify host plants. The plasticity of transient expression in plants, speed of scalability and relatively low capital costs, highlight the great potential of this technology in the future of human and animal health.

[1]  G. Lomonossoff,et al.  Fine-tuning levels of heterologous gene expression in plants by orthogonal variation of the untranslated regions of a nonreplicating transient expression system , 2014, Plant biotechnology journal.

[2]  Johannes F. Buyel,et al.  Plant Molecular Farming – Integration and Exploitation of Side Streams to Achieve Sustainable Biomanufacturing , 2019, Front. Plant Sci..

[3]  S. Schillberg,et al.  Critical Analysis of the Commercial Potential of Plants for the Production of Recombinant Proteins , 2019, Front. Plant Sci..

[4]  F. Altmann,et al.  N-Glycosylation engineering of plants for the biosynthesis of glycoproteins with bisected and branched complex N-glycans , 2011, Glycobiology.

[5]  Jacqueline MacDonald,et al.  The case for plant-made veterinary immunotherapeutics. , 2016, Biotechnology advances.

[6]  A. Laliberté,et al.  Production of Biopharmaceuticals in Nicotiana benthamiana—Axillary Stem Growth as a Key Determinant of Total Protein Yield , 2019, Front. Plant Sci..

[7]  Frank Sainsbury,et al.  A protease activity-depleted environment for heterologous proteins migrating towards the leaf cell apoplast. , 2012, Plant biotechnology journal.

[8]  N. Ranson,et al.  Plant-Made Nervous Necrosis Virus-Like Particles Protect Fish Against Disease , 2019, Front. Plant Sci..

[9]  G. Lomonossoff,et al.  Virus-Derived Vectors for the Expression of Multiple Proteins in Plants. , 2016, Methods in molecular biology.

[10]  Sylvain Marcel,et al.  Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals. , 2015, Plant biotechnology journal.

[11]  Frank Sainsbury,et al.  Protection of Recombinant Mammalian Antibodies from Development-Dependent Proteolysis in Leaves of Nicotiana benthamiana , 2013, PloS one.

[12]  G. Lomonossoff,et al.  A method for rapid production of heteromultimeric protein complexes in plants: assembly of protective bluetongue virus-like particles. , 2013, Plant biotechnology journal.

[13]  G. Lomonossoff,et al.  Molecular pharming - VLPs made in plants. , 2016, Current opinion in biotechnology.

[14]  D. Stuart,et al.  Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine , 2017, Nature Communications.

[15]  H. Steinkellner,et al.  Advanced Plant-Based Glycan Engineering , 2018, Front. Bioeng. Biotechnol..

[16]  E. Rybicki,et al.  Production of complex viral glycoproteins in plants as vaccine immunogens , 2018, Plant biotechnology journal.

[17]  John E. Johnson,et al.  Structure-based design of peptide presentation on a viral surface: the crystal structure of a plant/animal virus chimera at 2.8 A resolution. , 1996, Folding & design.

[18]  Daniel F Voytas,et al.  Multiplexed, targeted gene editing in Nicotiana benthamiana for glyco-engineering and monoclonal antibody production. , 2016, Plant biotechnology journal.

[19]  Samuel Kariuki,et al.  The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings , 2014, PLoS neglected tropical diseases.

[20]  G. Lomonossoff,et al.  Extremely High-Level and Rapid Transient Protein Production in Plants without the Use of Viral Replication1 , 2008, Plant Physiology.

[21]  D. Maresch,et al.  Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants , 2016, Front. Plant Sci..

[22]  I. Rouiller,et al.  Morphological characterization of a plant-made virus-like particle vaccine bearing influenza virus hemagglutinins by electron microscopy. , 2018, Vaccine.

[23]  M. Kaiser,et al.  Activity‐based proteomics reveals nine target proteases for the recombinant protein‐stabilizing inhibitor Sl CYS8 in Nicotiana benthamiana , 2019, Plant biotechnology journal.

[24]  M. Montagu,et al.  An Agrobacterium-mediated transient gene expression system for intact leaves , 1997 .

[25]  E. Rybicki,et al.  Immunogenicity of plant‐produced African horse sickness virus‐like particles: implications for a novel vaccine , 2017, Plant biotechnology journal.

[26]  H. Mason,et al.  Chimeric 3’ flanking regions strongly enhance gene expression in plants , 2018, Plant biotechnology journal.

[27]  E. Rybicki.  Plant-made vaccines and reagents for the One Health initiative , 2017, Human vaccines & immunotherapeutics.

[28]  L. Vézina,et al.  The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza. , 2010, Plant biotechnology journal.

[29]  P. Lerouge,et al.  Transient co-expression for fast and high-yield production of antibodies with human-like N-glycans in plants. , 2009, Plant biotechnology journal.

[30]  George P. Lomonossoff,et al.  Plant-produced biopharmaceuticals: A case of technical developments driving clinical deployment , 2016, Science.

[31]  A. Osbourn,et al.  Engineering terpenoid production through transient expression in Nicotiana benthamiana , 2018, Plant Cell Reports.

[32]  L. Vézina,et al.  Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants. , 2015, Biotechnology Journal.

[33]  M. Kaiser,et al.  Three unrelated protease inhibitors enhance accumulation of pharmaceutical recombinant proteins in Nicotiana benthamiana , 2018, Plant biotechnology journal.

[34]  Marc‐André D'Aoust,et al.  Leaf proteome rebalancing in Nicotiana benthamiana for upstream enrichment of a transiently expressed recombinant protein. , 2015, Plant biotechnology journal.

[35]  G. Lomonossoff,et al.  Improved foreign gene expression in plants using a virus-encoded suppressor of RNA silencing modified to be developmentally harmless. , 2011, Plant biotechnology journal.

[36]  T. Monath.  Vaccines against diseases transmitted from animals to humans: A one health paradigm , 2013, Vaccine.

[37]  R. Menassa,et al.  Identification, Characterization and Down-Regulation of Cysteine Protease Genes in Tobacco for Use in Recombinant Protein Production , 2015, PloS one.

[38]  G. Lomonossoff,et al.  Cowpea mosaic virus: the plant virus-based biotechnology workhorse. , 2010, Annual review of phytopathology.

[39]  B. Guy,et al.  Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate—Two randomized Phase II clinical trials in 18 to 49 and ≥50 years old adults , 2019, PloS one.

[40]  Diego Orzaez,et al.  Multiple T-DNA Delivery to Plants Using Novel Mini Binary Vectors with Compatible Replication Origins. , 2017, ACS synthetic biology.

[41]  G. Lomonossoff,et al.  Transient expressions of synthetic biology in plants , 2014, Current opinion in plant biology.

[42]  J. Dale,et al.  Improving agroinfiltration-based transient gene expression in Nicotiana benthamiana , 2018, Plant Methods.

[43]  Rainer Fischer,et al.  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 , 2018, Plant biotechnology journal.

[44]  S. Streatfield,et al.  Plant‐produced candidate countermeasures against emerging and reemerging infections and bioterror agents , 2015, Plant biotechnology journal.

[45]  G. Lomonossoff,et al.  When plant virology met Agrobacterium: the rise of the deconstructed clones , 2015, Plant biotechnology journal.

[46]  Marc‐André D'Aoust,et al.  Recombinant protein susceptibility to proteolysis in the plant cell secretory pathway is pH‐dependent , 2018, Plant biotechnology journal.

[47]  Hadrien Peyret,et al.  Improving plant transient expression through the rational design of synthetic 5′ and 3′ untranslated regions , 2019, Plant Methods.

[48]  E. Rybicki,et al.  Plant molecular farming of virus-like nanoparticles as vaccines and reagents. , 2020, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[49]  Renate Kunert,et al.  In Planta Protein Sialylation through Overexpression of the Respective Mammalian Pathway , 2010, The Journal of Biological Chemistry.

[50]  S. Schillberg,et al.  Tackling Unwanted Proteolysis in Plant Production Hosts Used for Molecular Farming , 2016, Front. Plant Sci..