Intracellular mRNA regulation with self-assembled locked nucleic acid polymer nanoparticles

Anthony M. Rush, David A. Nelles, Angela P. Blum, Sarah A. Barnhill, Erick T. Tatro, Gene W. Yeo, Nathan C. Gianneschi*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

We present an untemplated, single-component antisense oligonucleotide delivery system capable of regulating mRNA abundance in live human cells. While most approaches to nucleic acid delivery rely on secondary carriers and complex multicomponent charge-neutralizing formulations, we demonstrate efficient delivery using a simple locked nucleic acid (LNA)-polymer conjugate that assembles into spherical micellar nanoparticles displaying a dense shell of nucleic acid at the surface. Cellular uptake of soft LNA nanoparticles occurs rapidly within minutes as evidenced by flow cytometry and fluorescence microscopy. Importantly, these LNA nanoparticles knockdown survivin mRNA, an established target for cancer therapy, in a sequence-specific fashion as analyzed by RT-PCR.

Original languageEnglish (US)
Pages (from-to)7615-7618
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number21
DOIs
StatePublished - May 28 2014

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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