Dendrimers are precisely structured macromolecules with unique architectural symmetry and multivalency, offering a promising solution to the delivery challenges of nucleic acid therapeutics. Here, we explore recent advances in dendrimer design that enable targeted delivery to hard-to-transfect cells and difficult-to-reach tissues.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to the full article PDF.
USD 39.95
Prices may be subject to local taxes which are calculated during checkout
References
Chen, J., Zhu, D., Liu, X. & Peng, L. Amphiphilic dendrimer vectors for RNA delivery: state-of-the-art and future perspective. Acc. Mater. Res. 3, 484–497 (2022).
Kannan, R. M., Nance, E., Kannan, S. & Tomalia, D. A. Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J. Intern. Med. 276, 579–617 (2014).
Zhou, J. et al. Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Mol. Ther. 19, 2228–2238 (2011).
Chen, J. et al. Synthesis and use of an amphiphilic dendrimer for siRNA delivery into primary immune cells. Nat. Protoc. 16, 327–351 (2021).
Chahal, J. S. et al. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc. Natl Acad. Sci. USA 113, E4133–E4142 (2016).
Daftarian, P. et al. Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells. Cancer Res. 71, 7452–7462 (2011).
Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).
Sun, Y. et al. In vivo editing of lung stem cells for durable gene correction in mice. Science 384, 1196–1202 (2024).
Zhang, D. et al. Targeted delivery of mRNA with one-component ionizable amphiphilic Janus dendrimers. J. Am. Chem. Soc. 143, 17975–17982 (2021).
Meshanni, J. A. et al. Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers. Nat. Commun. 16, 1806 (2025).
Acknowledgements
This research is supported by Singapore Ministry of Education (MOE-T2EP30124-0015), A*Star NATi N05 (H24J5a0072), National University of Singapore-Campus France Partenariats Hubert Curien (PHC) Merlion program, the Ligue Nationale Contre le Cancer, the EU H2020 Marie Skłodowska-Curie Innovative Training Network ‘OLIGOMED’ (2021–2024) (No. 956070), the Horizon Europe Research and Innovation program Cancer Mission ‘HIT-GLIO’ (2023–2027) (No. 101136835) and the European Cooperation of Science and Technology (COST) Action CA21113 ‘Gene Editing for the treatment of Human Diseases’.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Ni, Q., Wu, J., Galanakou, C. et al. Dendrimer engineering to overcome delivery challenges of nucleic acids. Nat Rev Bioeng 3, 806–807 (2025). https://doi.org/10.1038/s44222-025-00347-w
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s44222-025-00347-w
