The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm
Open accessAbstract
RNA therapeutics have the potential to resolve a myriad of genetic diseases. Lipid nanoparticles (LNPs) are among the most successful RNA delivery systems. Expanding their use for the treatment of more genetic diseases hinges on our ability to continuously evolve the design of LNPs with high potency, cellular-specific targeting, and low side effects. Overcoming the difficulty of releasing cargo from endocytosed LNPs remains a significant hurdle. Here, we investigate the fundamental properties of nonviral RNA nanoparticles pertaining to the activation of topological transformations of endosomal membranes and RNA translocation into the cytosol. We show that, beyond composition, LNP fusogenicity can be prescribed by designing LNP nanostructures that lower the energetic cost of fusion and fusion–pore formation with a target membrane. The inclusion of structurally active lipids leads to enhanced LNP endosomal fusion, fast evasion of endosomal entrapment, and efficacious RNA delivery. For example, conserving the lipid make-up, RNA–LNPs having cuboplex nanostructures are significantly more efficacious at endosomal escape than traditional lipoplex constructs.
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Cites
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Cited by
Ghosh, S., Fan, Y., Laufer, B. I., Stephenson, W., Zang, N., Lawrence, J., Lin, H. H., Sen, S., Miller, S. E., Chu, S., et al. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100303 · Cited by 3
Metadata
- Authors
- Zheng, L., Bandara, S. R., Tan, Z., & Leal, C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2023-06-26
- Volume
- 120
- Issue
- 27
- Pages
- e2301067120-e2301067120
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W4382047482
- Cited by
- 259
- References
- 78
- FWCI
- 19.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zheng, L., Bandara, S. R., Tan, Z., & Leal, C. (2023). Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2301067120
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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