Rational vaccinology with spherical nucleic acids

Shuya Wang, Lei Qin, Gokay Yamankurt, Kacper Skakuj, Ziyin Huang, Peng Cheng Chen, Donye Dominguez, Andrew Lee, Bin Zhang*, Chad A. Mirkin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


In the case of cancer immunotherapy, nanostructures are attractive because they can carry all of the necessary components of a vaccine, including both antigen and adjuvant. Herein, we explore how spherical nucleic acids (SNAs), an emerging class of nanotherapeutic materials, can be used to deliver peptide antigens and nucleic acid adjuvants to raise immune responses that kill cancer cells, reduce (or eliminate) tumor growth, and extend life in three established mouse tumor models. Three SNA structures that are compositionally nearly identical but structurally different markedly vary in their abilities to cross-prime antigen-specific CD8+ T cells and raise subsequent antitumor immune responses. Importantly, the most effective structure is the one that exhibits synchronization of maximum antigen presentation and costimulatory marker expression. In the human papillomavirus-associated TC-1 model, vaccination with this structure improved overall survival, induced the complete elimination of tumors from 30% of the mice, and conferred curative protection from tumor rechallenges, consistent with immunological memory not otherwise achievable. The antitumor effect of SNA vaccination is dependent on the method of antigen incorporation within the SNA structure, underscoring the modularity of this class of nanostructures and the potential for the deliberate design of new vaccines, thereby defining a type of rational cancer vaccinology.

Original languageEnglish (US)
Pages (from-to)10473-10481
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - 2019


  • cancer vaccinology
  • immunotherapy
  • nanotechnology
  • spherical nucleic acids
  • structural design

ASJC Scopus subject areas

  • General


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