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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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
Pages (from-to)2124-2131
Number of pages8
JournalBioconjugate Chemistry
Volume27
Issue number9
DOIs
Publication statusPublished - Sep 21 2016

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ASJC Scopus subject areas

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

Cite this

Barnaby, S. N., Perelman, G. A., Kohlstedt, K. L., Chinen, A. B., Schatz, G. C., & Mirkin, C. A. (2016). Design Considerations for RNA Spherical Nucleic Acids (SNAs). Bioconjugate Chemistry, 27(9), 2124-2131. https://doi.org/10.1021/acs.bioconjchem.6b00350