Conjugation Chemistry-Dependent T-Cell Activation with Spherical Nucleic Acids

Kacper Skakuj, Shuya Wang, Lei Qin, Andrew Lee*, Bin Zhang, Chad A. Mirkin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Spherical nucleic acids (SNAs) can be potent sequence-specific stimulators of antigen presenting cells (APCs). When loaded with peptide antigens, they can be used to activate the immune system to train T-cells to specifically kill cancer cells. Herein, the role of peptide chemical conjugation to the DNA, which is used to load SNAs with antigens via hybridization, is explored in the context of APC activation. Importantly, though the antigen chemistry does not impede TLR-9 regulated APC activation, it significantly augments the downstream T-cell response in terms of both activation and proliferation. A comparison of three linker types, (1) noncleavable, (2) cleavable but nontraceless, and (3) traceless, reveals up to an 8-fold improvement in T-cell proliferation when the traceless linker is used. This work underscores the critical importance of the choice of conjugation chemistry in vaccine development.

Original languageEnglish (US)
Pages (from-to)1227-1230
Number of pages4
JournalJournal of the American Chemical Society
Volume140
Issue number4
DOIs
StatePublished - Jan 31 2018

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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