articleProceedings of the National Academy of SciencesJun 26, 2023GREEN OA

Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm

LZLining ZhengSRSarith R. BandaraZTZhengzhong TanCLCecília Leal

University of Illinois Urbana-Champaign

PubMed
Indexed incrossrefpubmed

Abstract

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…

Citation impact

215
total citations
FWCI
31.25
Percentile
100%
References
84
Citations per year

Authors

4

Topics & keywords

Topics
Keywords
  • Endosome
  • RNA
  • Cell biology
  • Lipid bilayer fusion
  • Cytoplasm
  • Cytosol
  • Chemistry
  • Nanotechnology
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