Edible mrna vaccine in lettuce chloroplasts

Messenger RNA (mRNA) vaccines hold promise for creating new and improved immunizations; however, their delivery is challenging in terms of compliance, reactogenicity, cost and scalability.

In response to ‘the ultimate bioengineering challenge’ competition, we propose an edible mRNA vaccine platform using lettuce chloroplasts. Access through your institution Buy or subscribe

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are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Han, J. et al.

Chloroplast display of subunit vaccines and their efficacy via oral administration. _Int. J. Biol. Macromol._ 258, 129125 (2024). Article  MATH  Google Scholar  * Kanagaraj, A. P., Verma, D.

& Daniell, H. Expression of dengue-3 premembrane and envelope polyprotein in lettuce chloroplasts. _Plant Mol. Biol._ 76, 323–333 (2011). Article  Google Scholar  * Jawalagatti, V.,

Kirthika, P. & Lee, J. H. Oral mRNA vaccines against infectious diseases- a bacterial perspective [invited]. _Front. Immunol._ 13, 884862 (2022). Article  Google Scholar  * Ruhlman, T.,

Verma, D., Samson, N. & Daniell, H. The role of heterologous chloroplast sequence elements in transgene integration and expression. _Plant Physiol._ 152, 2088–2104 (2010). Article 

Google Scholar  * Ruhlman, T., Ahangari, R., Devine, A., Samsam, M. & Daniell, H. Expression of cholera toxin B–proinsulin fusion protein in lettuce and tobacco chloroplasts – oral

administration protects against development of insulitis in non‐obese diabetic mice. _Plant Biotechnol. J._ 5, 495–510 (2007). Article  Google Scholar  * Immethun, C. M. et al. Physical,

chemical, and metabolic state sensors expand the synthetic biology toolbox for _Synechocystis_ sp. PCC 6803. _Biotechnol. Bioeng._ 114, 1561–1569 (2017). Article  MATH  Google Scholar  *

Mulo, P., Sicora, C. & Aro, E.-M. Cyanobacterial _psbA_ gene family: optimization of oxygenic photosynthesis. _Cell. Mol. Life Sci._ 66, 3697–3710 (2009). Article  Google Scholar  *

Stelljes, C. & Koenig, F. Specific binding of D1 protein degradation products to the _psbAI_ promoter in _Synechococcus_ sp. strain PCC 7942. _J. Bacteriol._ 189, 1722–1726 (2007).

Article  Google Scholar  * Stratmann, T. Cholera toxin subunit B as adjuvant — an accelerator in protective immunity and a break in autoimmunity. _Vaccines_ 3, 579–596 (2015). Article  MATH

  Google Scholar  * Farache, J. et al. Luminal bacteria recruit CD103+ dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. _Immunity_ 38, 581–595

(2013). Article  Google Scholar  * Nawaz, N. et al. Lysozyme and its application as antibacterial agent in food industry. _Molecules_ 27, 6305 (2022). Article  MATH  Google Scholar  * Svab,

Z. & Maliga, P. High-frequency plastid transformation in tobacco by selection for a chimeric aadA gene. _Proc. Natl Acad. Sci. USA_ 90, 913–917 (1993). Article  MATH  Google Scholar 

Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Westlake University, Hangzhou, China Carson Campbell * University of Chicago, Chicago, IL, USA Esteban Azagra Authors *

Carson Campbell View author publications You can also search for this author inPubMed Google Scholar * Esteban Azagra View author publications You can also search for this author inPubMed 

Google Scholar CONTRIBUTIONS The authors contributed equally to the preparation of this manuscript. CORRESPONDING AUTHORS Correspondence to Carson Campbell or Esteban Azagra. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Campbell, C., Azagra, E.

Edible mRNA vaccine in lettuce chloroplasts. _Nat Rev Bioeng_ 3, 264–266 (2025). https://doi.org/10.1038/s44222-025-00299-1 Download citation * Published: 14 April 2025 * Issue Date: April

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