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 language | English (US) |
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Pages (from-to) | 2011-2021 |
Number of pages | 11 |
Journal | Molecular Therapy |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2008 |
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery