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Next-generation materials for nucleic acid delivery

Nature Reviews Materials volume 10, pages 490–499 (2025)Cite this article

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Efficient and targeted delivery of nucleic acids is critical for realizing the full therapeutic potential of gene editing, vaccines and RNA-based drugs, and emerging delivery platforms offer innovative solutions through their diverse architectures, tunable properties and distinct biological interactions. In this Viewpoint, researchers working across different delivery platforms — including lipid nanoparticles, synthetic polymers, peptide amphiphiles, coacervate microdroplets, DNA nanostructures and extracellular vesicles — discuss the most promising directions and the main challenges in shaping the future of nucleic acid delivery.

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Fig. 1: Materials for nucleic acid delivery.

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Acknowledgements

R.v.d.M. is supported by Dutch Research Council (NWO) Vidi grant (no. 19681). A.M. is supported by research grants from the Nucleic Acid Therapeutics Initiative (NATi, grant number H24J5a0070) of the Singapore Agency for Science, Technology, and Research (ASTAR), and by the Singapore National Research Foundation (NRF) through its Competitive Research Program (grant number NRF-CRP30-2023-0004). P.L. gratefully acknowledges funding from the Swiss National Science Foundation (215227, 229688) and thanks the Faculties of Science and of Medicine of the University of Bern for the financial support to the Center for Extracellular Vesicles (EVR), the EVR Board, and C. Zivko for the critical reading of the contribution. I.L.-S. and J.M. thank the Spanish Agencia Estatal de Investigación (PID2020-117143RB-I00, PDC2021-121192-I00, PID2023-152181OB-I00), Fundación la Caixa (TROPIC, HR23-00221), the ERC (DYNAP-677786), the European Innovation Council (Pathfinder (CAR T-REX, 2022-101099867), Transition (TraffikGene-Tx, 2022-101113110)) the Xunta de Galicia (ED431G 2023/03, ED431C 2024/03, IN855A 2021/06, the Oportunius Program (GAIN)), and the European Regional Development Fund (ERDF).

Author information

Authors and Affiliations

  1. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands

    Roy van der Meel

  2. Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, the Netherlands

    Roy van der Meel

  3. Department of Chemistry, Stanford University, Stanford, CA, USA

    Paul A. Wender

  4. Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA

    Paul A. Wender

  5. Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany

    Olivia M. Merkel

  6. Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, Munich, Germany

    Olivia M. Merkel

  7. Ludwig-Maximilians-Universität München (Member of the German Center for Lung Research (DZL)), Munich, Germany

    Olivia M. Merkel

  8. Cluster for Nucleic Acid Therapeutics Munich (CNATM), Munich, Germany

    Olivia M. Merkel

  9. Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain

    Irene Lostalé-Seijo & Javier Montenegro

  10. Center for Sustainable Materials (SusMat), School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore

    Ali Miserez

  11. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

    Ali Miserez

  12. Department of Chemistry, McGill University, Montreal, Quebec, Canada

    Quentin Laurent & Hanadi Sleiman

  13. University Grenoble Alpes, CNRS, DCM UMR 5250, Grenoble, France

    Quentin Laurent

  14. Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland

    Paola Luciani

Authors
  1. Roy van der Meel
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  2. Paul A. Wender
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  3. Olivia M. Merkel
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  4. Irene Lostalé-Seijo
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  5. Javier Montenegro
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  6. Ali Miserez
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  7. Quentin Laurent
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  8. Hanadi Sleiman
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  9. Paola Luciani
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Contributions

Roy van der Meel is an Associate Professor of Precision Medicine at the Department of Biomedical Engineering of the Eindhoven University of Technology in the Netherlands. His group focuses on engineering RNA-based nanomedicines to precisely regulate immune cell function, aiming to treat diseases such as cancer and autoimmune disorders.

Paul A. Wender is the Francis W. Bergstrom Professor of Chemistry and Professor, by courtesy, of Chemical and Systems Biology at Stanford University. His research interests focus on addressing unsolved problems in chemistry, biology, medicine and materials science using new computational tools, new reactions and new materials design strategies.

Olivia M. Merkel has been a Professor of Drug Delivery at Ludwig-Maximilians-Universität Munich in Germany since 2015, Chair since 2022, and Co-Director of the Department of Pharmacy since 2024. She is a Registered Pharmacist and received her MS (2006) and PhD (2009) in Pharmaceutical Technology. Her research focuses mainly on RNA formulation and pulmonary delivery for the treatment of a variety of lung diseases. She is a scientific advisory board member of Coriolis Pharma, AMW, and Corden Pharma, as well as a co-founder of RNhale.

Javier Montenegro is a Titular Professor and Oportunius Professor at the Center for Research in Biological Chemistry and Molecular Materials (CIQUS) at the University of Santiago de Compostela, Spain. His research focuses on functional supramolecular systems, including synthetic materials for the delivery of nucleic acids and proteins, superchaotropic membrane carriers, 2D peptide self-assemblies, and the bottom–up reconstruction of simple cytoskeleton mimetics from synthetic building blocks.

Irene Lostalé-Seijo is a research associate in Montenegro’s group at CIQUS, where she works on the biology-related projects. Her research interests are focused on the development of new carriers for the delivery of biomolecules into cells.

Ali Miserez is the President’s Chair Professor in Biomimetic and Bioinspired Materials in the School of Materials Science and Engineering and the School of Biological Sciences at Nanyang Technological University (NTU), Singapore, where he is also the founding Director of the Center for Sustainable Materials. His research aims at revealing the molecular, physico-chemical and structural principles from unique biological materials and at translating their molecular design into novel biomimetic materials, including for healthcare applications such as intracellular drug delivery vehicles.

Quentin Laurent is a postdoctoral researcher at the University Grenoble Alpes in France working on biomolecular assemblies. His research lies at the crossroad between organic chemistry, biomolecules and complex architectures to probe and influence biological objects.

Hanadi Sleiman is a Professor and Canada Research Chair in DNA nanoscience at the Department of Chemistry, McGill University, Canada. Her research focuses on designing DNA nanomaterials for the targeted delivery of nucleic acid therapies and the creation of protein mimics, as well as discovering the fundamental principles of DNA supramolecular chemistry.

Paola Luciani is Full Professor of Pharmaceutical Technology at the University of Bern, Switzerland. Her laboratory’s research focuses on developing bio-inspired and bioderived drug delivery systems for patient-centric therapies. She contributed to the establishment of the interfaculty Center for Extracellular Research (EVR) of the University of Bern and serves as an expert in Pharmaceutical Quality at the Swiss Agency for Therapeutic Products and as a member of the European Pharmacopeia’s NANO (Nanomedicine) Working group.

Corresponding authors

Correspondence to Roy van der Meel, Paul A. Wender, Olivia M. Merkel, Irene Lostalé-Seijo, Javier Montenegro, Ali Miserez, Quentin Laurent, Hanadi Sleiman or Paola Luciani.

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Competing interests

R.v.d.M. is listed as inventor on patent applications WO2022268913A1, WO2023233042A1, WO2023227682A1 and WO2023046931A1, related to apolipoprotein nanoparticle technology. P.A.W. is a co-inventor on several patents and patent applications filed by Stanford University related to the discussed topic (12215341, 20240277854, 20240277870, 20240148858, 11931416, 20220143199, 20220088163, 10961263, 20200308200, 10654875, 20180319825 and 20180028688) and is a co-founder of N1 Life, a delivery company. O.M.M. is a co-founder of RNhale GmbH, a Scientific Board Member for Coriolis Pharma GmbH, AMW GmbH, and Corden Pharma International GmbH, and an Advisor for PARI Pharma GmbH, Boehringer-Ingelheim International GmbH, and AbbVie Deutschland GmbH & Co. KG on unrelated projects. None of these companies were involved in or funded the research presented here. J.M. and I.L.-S. are listed as inventors on a patent application (WO2023247781A1) related to peptide amphiphiles. P.L. is a board member of the Center for Extracellular Vesicle Research (EVR) of the University of Bern; has consulted and received research grants from Lipoid GmbH, Sanofi-Aventis Deutschland and DSM Nutritional Products Ltd on unrelated projects; and has received research grants from PPM Services S.A on unrelated projects. The other authors declare no competing interests.

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van der Meel, R., Wender, P.A., Merkel, O.M. et al. Next-generation materials for nucleic acid delivery. Nat Rev Mater 10, 490–499 (2025). https://doi.org/10.1038/s41578-025-00814-1

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