mRNA-LNP therapeutics for obesity: weight loss with metabolic repair

Obesity involves dysfunction in metabolic tissues that is not always fully corrected by weight loss. An mRNA-lipid nanoparticle platform might offer a programmable approach for in situ production of therapeutic proteins directly in target tissues, enabling endocrine signalling, adipose remodelling and multi-pathway metabolic regulation

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Subjects

• Metabolomics
• Endocrine system and metabolic diseases

References

1. Lingvay, I., Cohen, R. V., le Roux, C. W. & Sumithran, P. Obesity in adults. Lancet404, 972–987 (2024)

   Article 
   CAS 
   PubMed 
   Google Scholar 

2. Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med.387, 205–216 (2022)

   Article 
   CAS 
   PubMed 
   Google Scholar 

3. Recasens-Alvarez, C., Heap, G. & Green, G. The evolution of the obesity drug market. Nat. Rev. Drug Discov.24, 902–903 (2025)

   Article 
   CAS 
   PubMed 
   Google Scholar 

4. Liu, C. et al. mRNA-based cancer therapeutics. Nat. Rev. Cancer23, 526–543 (2023)

   Article 
   PubMed 
   Google Scholar 

5. Cheng, Q. et al. In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma. Proc. Natl Acad. Sci. USA120, e2313009120 (2023)

   Article 
   CAS 
   PubMed 
   PubMed Central 
   Google Scholar 

6. Cullis, P. R. & Felgner, P. L. The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug Discov.23, 709–722 (2024)

   Article 
   CAS 
   PubMed 
   Google Scholar 

7. Han, X. et al. In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors. Nat. Commun.15, 1762 (2024)

   Article 
   CAS 
   PubMed 
   PubMed Central 
   Google Scholar 

8. Ma, B. et al. A simplified three-tailed N-alkyl phosphoramidate lipid platform enables inguinal adipose-accumulated mRNA delivery for anti-obesity therapy. Adv. Sci.13, e17672 (2026)

   Article 
   CAS 
   Google Scholar 

9. Myerson, M. & Paparodis, R. D. Pharmacotherapy of weight-loss and obesity with a focus on GLP 1-receptor agonists. J. Clin. Pharmacol.64, 1204–1221 (2024)

   Article 
   CAS 
   PubMed 
   Google Scholar 

10. Stewart, W. et al. A combinatorial siRNA and mRNA approach for obesity treatment using targeting lipid nanoparticles. J. Control. Release383, 113857 (2025)

    Article 
    CAS 
    PubMed 
    Google Scholar 

Download references

Acknowledgements

C.L. acknowledges support from the National University of Singapore (grant numbers A-0010330-00-00 and A-0010330-01-00 to C.L.), the Joint Seed Funding between the National University of Singapore and Korea University (KU-NUS Joint Seed Funding, grant number A-8004676-00-00 to C.L.) and the Singapore Ministry of Education Academic Research Fund Tier 1 (grant number A-8004773-00-00 to C.L.). D.J.S. acknowledges support from the National Institutes of Health (R01EB025192, R01CA269787)

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Authors and Affiliations

1. Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore

   Jun Liao & Chuang Liu

2. Department of Biomedical Engineering, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA

   Lukas Farbiak & Daniel J. Siegwart

3. Department of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA

   Lukas Farbiak & Daniel J. Siegwart

4. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

   Chuang Liu

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1. Jun LiaoView author publications

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2. Lukas FarbiakView author publications

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3. Daniel J. SiegwartView author publications

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4. Chuang LiuView author publications

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Competing interests

D.J.S. discloses financial interests in ReCode Therapeutics, Signify Bio, Jumble Therapeutics and Pegasus Bio. L.F. discloses financial interests in Signify Bio. The other authors declare no competing interests

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Liao, J., Farbiak, L., Siegwart, D.J. et al. mRNA-LNP therapeutics for obesity: weight loss with metabolic repair.
Nat Rev Endocrinol (2026). https://doi.org/10.1038/s41574-026-01297-y

• Published:14 August 2026

• Version of record:14 August 2026

• DOI
  :https://doi.org/10.1038/s41574-026-01297-y