Sequence Multiplicity within Spherical Nucleic Acids

Ziyin N. Huang, Lisa E. Cole, Cassandra E. Callmann, Shuya Wang, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The synthesis and evaluation of spherical nucleic acids (SNAs) incorporating two physically and chemically distinct classes of oligonucleotides (ODNs) at programmed ratios are described. These SNAs are single entity agents that enter the same target cell at defined stoichiometries, and as such allow one to control important cell signaling and regulatory processes. To study the effect of sequence multiplicity within such structures, we synthesized SNAs consisting of a mixture of class A CpG and class B CpG, immunostimulatory ODNs that activate two different toll-like receptor 9 signaling pathways, each in a sequence-specific fashion. These dual-CpG SNAs exhibit high cellular uptake and codelivery of the two ODNs, relative to mixtures of the linear ODN counterparts, and remain highly associated inside the cell over time. Furthermore, the dual-CpG SNAs augment dendritic cell maturation, compared to the same amounts of oligonucleotides delivered in linear or SNA form but not conjugated to one another. Consequently, these structures constitute a platform for designing oligonucleotide-based combination therapeutics with highly tailorable activities.

Original languageEnglish (US)
Pages (from-to)1084-1092
Number of pages9
JournalACS nano
Issue number1
StatePublished - Jan 28 2020


  • DNA nanotechnology
  • biotechnology
  • immunotherapy
  • microscopy
  • spherical nucleic acids

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)


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