MIS416 as a siRNA Delivery System with the Ability to Target Antigen-Presenting Cells

Nucleic Acid Ther. 2018 Aug;28(4):225-232. doi: 10.1089/nat.2017.0695. Epub 2018 Jun 12.

Abstract

MIS416 is a microparticulate formulation derived from propionibacterium acnes cell wall skeletons with intrinsic adjuvant activity. Conjugates of MIS416-SS-peptide containing a disulfide linkage facilitate the cytoplasmic delivery and release of peptides in antigen-presenting cells (APCs). We hypothesized that MIS416-siRNA (small interfering RNA) conjugates, containing a disulfide linkage between MIS416 and the siRNA, would allow cytoplasmic release of siRNA in APCs. MIS416-SS-siStat3 conjugates added to cell culture medium of monolayers of DCs in culture flasks successfully targeted Stat3 mRNA in DCs in vitro without transfection, downregulating Stat3 mRNA and protein levels. These results suggest that MIS416-SS-siRNA conjugates can be used as a novel siRNA delivery system for the knockdown of mRNA levels in APCs.

Keywords: Stat3; delivery; dendritic cells; gene silencing; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / immunology
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / therapeutic use
  • Dendritic Cells / immunology
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Humans
  • Immunoconjugates / therapeutic use
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / therapeutic use
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / immunology

Substances

  • Cancer Vaccines
  • Immunoconjugates
  • MIS416 vaccine
  • RNA, Small Interfering
  • STAT3 Transcription Factor