NEWCOTIANA - Developing Multipurpose Nicotiana Crops for Molecular Farming using New Plant Breeding Techniques
Published July 19, 2021 | Version v1
Journal article Open

Contributions of the international plant science community to the fight against infectious diseases inhumans—part 2: Affordable drugs in edible plants forendemic and re-emerging diseases

Creators

  • 1. Department of Crop and Forest Sciences, University of Lleida-Agrotecnio CERCA Center, Lleida, Spain
  • 2. Instituto de Tecnologia Quíımica e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
  • 3. Plant Genetic Engineering Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, India
  • 4. Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany
  • 5. Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany; Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany
  • 6. Centro de Analise Proteomicas e Bioquımicas de Brasılia, Universidade Catolica de Brasılia, Brasılia, Brazil
  • 7. School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • 8. Department of Chemical Engineering, University of California, Davis, Davis, CA, USA
  • 9. Industrial Biotechnology and Food Solutions, VTT Technical Research Centre of Finland Ltd, Espoo, Finland
  • 10. International Centre for Genetic Engineering and Biotechnology, New Delhi, India
  • 11. Brazilian Agriculture Research Corporation, Embrapa Genetic Resources and Biotechnology and National Institute of Science and Technology Synthetic in Biology,Parque Estação Biologica, Brasilia, Brazil
  • 12. Department of Biological Chemistry, John Innes Centre, Norwich, UK
  • 13. Institute for Infection and Immunity, St. George's University of London, London, UK
  • 14. Department of Chemical Engineering, University of California, Davis, Davis, CA, USA; Global HealthShare Initiative, University of California, Davis, Davis, CA, USA
  • 15. Molecular Targets Program, Center for Cancer Research, National Cancer Institute, and Natural Products Branch, Developmental Therapeutics Program, Division ofCancer Treatment and Diagnosis, National Cancer Institute, NIH, Frederick, MD, USA
  • 16. Instituto de Tecnologia Quíımica e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal; Department of Biological Chemistry, John Innes Centre, Norwich, UK
  • 17. Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany; Institute for Phytopathology, Justus-Liebig-University Giessen, Giessen, Germany
  • 18. Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
  • 19. Department of Chemical Engineering, University of California, Davis, Davis, CA, USA; Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA
  • 20. TRM Ltd, Scarborough, UK
  • 21. Laboratory of Nematology, Plant Sciences Group, Wageningen University and Research, Wageningen, The Netherlands
  • 22. Department of Crop and Forest Sciences, University of Lleida-Agrotecnio CERCA Center, Lleida, Spain; ICREA, Catalan Institute for Research and Advanced Studies, Barcelona, Spain

Description

The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re-emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical-grade protein drugs in leaves to treat infectious diseases and the long-term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection.

Notes

The authors would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (project AGL2017-85377-R), the Spanish Ministry of Science, Innovation and Universities (projects RTI2018-097613-B-I00 and PGC2018-097655-B-I00), the EU Horizon 2020 project Pharma-Factory (774078) and the Generalitat de Catalunya (Grups Consolidats2017-SGR828); Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Departament d'Empresa i Coneixement de la Generalitat de Catalunya (PANDÈMIES 2020); Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular funded by FEDER funds through COMPETE2020)—Programa Operacional Competitividade e Internacionalização (POCI) and by the FCT (Portugal) through the R&D Unit, UIDB/04551/2020 (GREEN-IT—Bioresources for Sustainability); UKIERI and the Hotung Foundation for sustained support of the Bharathiar University / St. George's Univ. of London collaboration and the Molecular Immunology Unit at St. George's Univ. of London. The Max Planck Society, the EU Horizon 2020 project Newcotiana (760331-2) and a grant from the European Research Council (ERC-ADG-2014; grant agreement 669982) to RB. KMOC, RMT and STH acknowledge support from the InnCoCells project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement 101000373. PSS, KAM, RF and SN are partially supported by a CRAFT award (COVID-19 Research Accelerator Funding Track) by the University of California Davis. KAM and SN were partially supported by NASA Space Technology Research (award number NNX17AJ31G) and by the Translational Research Institute through NASA (grant number NNX16AO69A); EMBRAPA (Brazilian Agricultural Corporation), INCT BioSyn (National Institute of Science and Technology in Synthetic Biology), CNPq, CAPES, Brazilian Ministry of Health, FAPDFnd Universidade Católica de Brasília (UCB), Brasília, Brazil; BBSRC Grant BB/L020955/1, the JIC Strategic Programme Grant 'Molecules from Nature – Enhanced Research Capacity' (BBS/E/J/000PR9794), the John Innes Foundation and the Department of Health and Social Care using UK Aid funding managed by the BBSRC; and The Austrian Science Fund FWF (project W1224). TTW Veni Grant 16740 from the Netherlands Organization for Scientific Research. Research in the Daniell laboratory was supported by NIH grants R01 GM 63879, R01 107904, R01 HL 109442, R01 133191 and grants from Bayer, Novo Nordisk and Shire/Takeda. The National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, through the Science Moving TowArds Research Translation and Therapy (SMARTT) programme contracts # HHSN268201600014C, HHSN268201600011C supported IND enabling regulatory, toxicology and pharmacokinetic studies. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author (s) and do not necessarily reflect the views of the University of California, Davis, National Aeronautics and Space Administration (NASA) or the Translational Research Institute for Space Health (TRISH). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Views expressed in this article are those of the authors and do not necessarily reflect those of the employing institutions or the UK Department of Health and Social Care.

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Funding

Newcotiana – Developing Multipurpose Nicotiana Crops for Molecular Farming using New Plant Breeding Techniques 760331
European Commission
Pharma-Factory – Building the product pipeline for commercial demonstration of Plant Molecular Factories 774078
European Commission