Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-11-21
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1525-0024
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2011-21
pubmed:meshHeading
pubmed-meshheading:18813280-Animals, pubmed-meshheading:18813280-Antigen-Presenting Cells, pubmed-meshheading:18813280-Biological Markers, pubmed-meshheading:18813280-Bone Marrow, pubmed-meshheading:18813280-Cell Proliferation, pubmed-meshheading:18813280-Cells, Cultured, pubmed-meshheading:18813280-Cytokines, pubmed-meshheading:18813280-Dendritic Cells, pubmed-meshheading:18813280-Female, pubmed-meshheading:18813280-Gene Expression Regulation, pubmed-meshheading:18813280-Imines, pubmed-meshheading:18813280-Lactic Acid, pubmed-meshheading:18813280-Mice, pubmed-meshheading:18813280-Mice, Inbred BALB C, pubmed-meshheading:18813280-Plasmids, pubmed-meshheading:18813280-Polyethylenes, pubmed-meshheading:18813280-Polyglycolic Acid, pubmed-meshheading:18813280-RNA, Small Interfering, pubmed-meshheading:18813280-T-Lymphocytes, pubmed-meshheading:18813280-Up-Regulation, pubmed-meshheading:18813280-Vaccines, DNA
pubmed:year
2008
pubmed:articleTitle
Efficient modulation of T-cell response by dual-mode, single-carrier delivery of cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells.
pubmed:affiliation
Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural