Efficient modulation of T-cell response by dual-mode, single-carrier delivery of cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells

Mol Ther. 2008 Dec;16(12):2011-21. doi: 10.1038/mt.2008.206. Epub 2008 Sep 23.


Controlled modulation of T-cell response during immunotherapy, especially the balance between T helper 1 (Th1) and Th2 responses, is critical for generating effective immune response. Here we report that dual delivery of interleukin 10 (IL-10)-targeted small interfering RNA (siRNA) and DNA vaccines to dendritic cells (DCs), using a single particle carrier, efficiently enhances immune response and modulates it toward a stronger Th1 phenotype. Surface-functionalized polymer microparticles (MPs) carrying both IL-10-targeted siRNA and DNA antigens exhibited effective gene silencing, DNA transfection, and synergistically enhanced upregulation of maturation markers in primary DCs leading to increased T-cell proliferation, in vitro. Mice immunized with these dual-delivery carriers demonstrated a significant "switch" toward Th1 response as evidenced by increase in interferon gamma (IFN-gamma) production and decrease in IL-4 production by CD4+ T cells. This further led to enhanced antiviral cytotoxic T-lymphocyte activity. Such dual siRNA-DNA delivery provides a novel strategy to precisely control the type and strength of T-cell response during immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism*
  • Biomarkers
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Gene Expression Regulation
  • Imines
  • Lactic Acid
  • Mice
  • Mice, Inbred BALB C
  • Plasmids / genetics
  • Polyethylenes
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RNA, Small Interfering / genetics*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Up-Regulation / immunology
  • Vaccines, DNA / genetics*
  • Vaccines, DNA / immunology*


  • Biomarkers
  • Cytokines
  • Imines
  • Polyethylenes
  • RNA, Small Interfering
  • Vaccines, DNA
  • poly(ethylene imine)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid