Design Considerations for RNA Spherical Nucleic Acids (SNAs)

Stacey N. Barnaby, Grant A. Perelman, Kevin L. Kohlstedt, Alyssa B. Chinen, George C. Schatz, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Ribonucleic acids (RNAs) are key components in many cellular processes such as cell division, differentiation, growth, aging, and death. RNA spherical nucleic acids (RNA-SNAs), which consist of dense shells of double-stranded RNA on nanoparticle surfaces, are powerful and promising therapeutic modalities because they confer advantages over linear RNA such as high cellular uptake and enhanced stability. Due to their three-dimensional shell of oligonucleotides, SNAs, in comparison to linear nucleic acids, interact with the biological environment in unique ways. Herein, the modularity of the RNA-SNA is used to systematically study structure-function relationships in order to understand how the oligonucleotide shell affects interactions with a specific type of biological environment, namely, one that contains serum nucleases. We use a combination of experiment and theory to determine the key architectural properties (i.e., sequence, density, spacer moiety, and backfill molecule) that affect how RNA-SNAs interact with serum nucleases. These data establish a set of design parameters for SNA architectures that are optimized in terms of stability.

Original languageEnglish (US)
Pages (from-to)2124-2131
Number of pages8
JournalBioconjugate Chemistry
Issue number9
StatePublished - Sep 21 2016

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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