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

Ankur Singh, Hui Nie, Bilal Ghosn, Hong Qin, Larry W. Kwak, Krishnendu Roy

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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 γ (IFN-γ) 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.

Original languageEnglish (US)
Pages (from-to)2011-2021
Number of pages11
JournalMolecular Therapy
Volume16
Issue number12
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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