Lipid Nanoparticle Spherical Nucleic Acids for Intracellular DNA and RNA Delivery

Andrew J. Sinegra, Michael Evangelopoulos, Jungsoo Park, Ziyin Huang, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Lipid nanoparticle SNAs (LNP-SNAs) have been synthesized for the delivery of DNA and RNA to targets in the cytoplasm of cells. Both the composition of the LNP core and surface-presented DNA sequences contribute to LNP-SNA activity. G-rich sequences enhance the activity of LNP-SNAs compared to T-rich sequences. In the LNP core, increased cholesterol content leads to greater activity. Optimized LNP-SNA candidates reduce the siRNA concentration required to silence mRNA by 2 orders of magnitude compared to liposome-based SNAs. In addition, the LNP-SNA architectures alter biodistribution and efficacy profiles in mice. For example, mRNA within LNP-SNAs injected intravenously is primarily expressed in the spleen, while mRNA encapsulated by LNPs (no DNA on the surface) was expressed primarily in the liver with a relatively small amount in the spleen. These data show that the activity and biodistribution of LNP-SNA architectures are different from those of conventional liposomal SNAs and therefore potentially can be used to target tissues.

Original languageEnglish (US)
Pages (from-to)6584-6591
Number of pages8
JournalNano letters
Volume21
Issue number15
DOIs
StatePublished - Aug 11 2021

Keywords

  • RNA
  • Spherical nucleic acids
  • drug delivery
  • lipid nanoparticles

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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