Duplex end breathing determines serum stability and intracellular potency of siRNA-Au NPs

Pinal C. Patel, Liangliang Hao, Weng Si Au Yeung, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Structural requirements of siRNA-functionalized gold nanoparticles (siRNA-Au NPs) for Dicer recognition and serum stability were studied. We show that the 3′ overhang on the nucleic acids of these particles is preferentially recognized by Dicer but also makes the siRNA duplexes more susceptible to nonspecific serum degradation. Dicer and serum nucleases show lower preference for blunt duplexes as opposed to those with 3′ overhangs. Importantly, gold nanoparticles functionalized with blunt duplexes with relatively less thermal breathing are up to 15 times more stable against serum degradation without compromising Dicer recognition. This increased stability leads to a 300% increase in cellular uptake of siRNA-Au NPs and improved gene knockdown.

Original languageEnglish (US)
Pages (from-to)1285-1291
Number of pages7
JournalMolecular Pharmaceutics
Volume8
Issue number4
DOIs
StatePublished - Aug 1 2011

Keywords

  • Dicer activity
  • GFP knockdown
  • gold nanoparticle
  • siRNA
  • siRNA stability

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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