Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Plant cell-based drug delivery enhances affordability of biologics

Nature Biotechnology volume 41, pages 1186–1187 (2023)Cite this article

Subjects

A Correspondence published recently in Nature Biotechnology discussed the socioeconomic potential and commercial feasibility of plant molecular farming1. This Correspondence also mentioned the risks of new products and platforms while leaving out discussion of important new biologic products made using plant biotechnology. Here, we highlight recent advances in plant molecular farming, focusing on methods of drug delivery (oral, topical, patches and chewing gum) and the advantages of using plant molecular farming methods to reduce production costs, thereby enhancing affordability and global access.

Oral delivery of protein drugs is one of the most challenging methods to develop, but it is the most preferred by patients. The mucosa of the human small intestine offers a large absorption surface area (30 m2). Protein drugs should be bioencapsulated for protection from degradation by stomach acids and enzymes, and the use of plant cells for delivery is ideally suited for this purpose. Human digestive enzymes cleave α-linkages, but plant cell wall polymers are linked by β-1,4–1,6 bonds, and therefore therapeutic proteins bioencapsulated within plant cell wall are protected from human digestion2,3,4,5,6. However, gut microbes produce enzymes that cleave the β-linkages of plant cell wall polymers to release the protein drugs2,3,4,5,6. The final challenge is delivery across the gut epithelium to the immune or circulatory system, which is accomplished by fusion to tags that are proteolytically cleaved or by direct delivery to circulation through the gut–liver axis. This approach has enabled alleviation of cardiovascular conditions by oral ACE2 (ref. 2), regulation of blood sugar levels by oral insulin in the same manner as natural insulin3 and acceleration of diabetic bone fracture healing by oral IGF-1 (ref. 4).

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: FDA-approved biologic drug delivery methods and percentage of each method since 2015.

References

  1. Benvenuto, E. et al. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01812-w (2023).

    Article  PubMed  Google Scholar 

  2. Daniell, H. et al. Biomaterials 233, 119750 (2020).

    Article  CAS  PubMed  Google Scholar 

  3. Daniell, H. et al. Biomaterials 298, 122142 (2023).

    Article  CAS  PubMed  Google Scholar 

  4. Park, J. et al. Biomaterials 233, 119591 (2020).

    Article  CAS  PubMed  Google Scholar 

  5. Srinivasan, A. et al. Plant Biotechnol. J. 19, 1952–1966 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Butterfield, J. S. S. et al. Cell. Immunol. https://doi.org/10.1016/j.cellimm.2023.104742 (2023).

    Article  PubMed  Google Scholar 

  7. Vickery, B. P. et al. N. Engl. J. Med. 379, 1991–2001 (2018).

    Article  PubMed  Google Scholar 

  8. Greenhawt, M. et al. N. Engl. J. Med. 388, 1755–1766 (2023).

    Article  CAS  PubMed  Google Scholar 

  9. Daniell, H. et al. Mol. Ther. 30, 1966–1978 (2022).

    Article  CAS  PubMed  Google Scholar 

  10. Daniell, H. et al. Biomaterials 288, 121671 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. DiMasi, J. A., Grabowski, H. G. & Hansen, R. W. J. Health Econ. 47, 20–33 (2016).

    Article  PubMed  Google Scholar 

  12. Loembé, M. M. & Nkengasong, J. N. Immunity 54, 1353–1362 (2021).

    Article  Google Scholar 

  13. Rome, B. N., Egilman, A. C. & Kesselheim, A. S. J. Am. Med. Assoc. 327, 2145–2147 (2022).

    Article  Google Scholar 

  14. Hopkins, J. S. New $2.9 million gene therapy promises to remake hemophilia treatment. The Wall Street Journal (29 June 2023).

  15. Naddaf, M. Nature 612, 388–389 (2022).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Research from the Daniell lab on oral or topical delivery was supported US National Institutes of Health grant R01 HL 107904 and Commonwealth of Pennsylvania, Department of Community and Economic Development grants.

Author information

Authors and Affiliations

  1. Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Henry Daniell & Rachel J. Kulchar

  2. Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN, USA

    Roland W. Herzog

  3. Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA

    Mike Kulis

  4. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Kam W. Leong

Authors
  1. Henry Daniell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel J. Kulchar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roland W. Herzog
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mike Kulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kam W. Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.D. wrote the first and edited subsequent drafts. M.K. and H.D. wrote the peanut allergy sections. R.W.H. and H.D. wrote the hemophilia sections. R.J.K. collected data on FDA-approved biologics and created Fig. 1. K.W.L. edited several drafts.

Corresponding author

Correspondence to Henry Daniell.

Ethics declarations

Competing interests

H.D. and R.W.H. are patentees in plant-based oral tolerance induction and were previously funded by Novo Nordisk, Bayer, Shire and Takeda. H.D. is a patentee in chewing gum or oral drug delivery technologies using plant cells, and several industry partnerships for advancing clinical trials are in progress. A complete list of patents is available at http://scholar.google.com/citations?user=7sow4jwAAAAJ&hl=en. All other authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Daniell, H., Kulchar, R.J., Herzog, R.W. et al. Plant cell-based drug delivery enhances affordability of biologics. Nat Biotechnol 41, 1186–1187 (2023). https://doi.org/10.1038/s41587-023-01899-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41587-023-01899-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research