Journal
BIOMATERIALS
Volume 30, Issue 6, Pages 1232-1245Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.10.064
Keywords
Copolymer; Gene expression; Leukocyte; Pluronics
Funding
- National Institutes of Health [R01 CA116591]
- American Heart Association fellowship [06100652]
- Supratek Pharma Inc.
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DNA vaccines can be greatly improved by polymer agents that simultaneously increase transgene expression and activate immunity. We describe here Pluronic P85 (P85), a triblock copolymer of ethylene oxide (EO) and propylene oxide (PO) EO26-PO40-EO26. Using a mouse model we demonstrate that co-administration of a bacterial plasmid DNA with P85 in a skeletal muscle greatly increases gene expression in the injection site and distant organs, especially the draining lymph nodes and spleen. The reporter expression colocalizes with the specific markers of myocytes and keratinocytes in the muscle, as well as dendritic cells (DCs) and macrophages in the muscle, lymph nodes and spleen. Furthermore, DNA/P85 and P85 alone increase the systemic expansion of CD11c(+) (DC), and local expansion of CD11c(+), CD14(1) (macrophages) and CD49b(1) (natural killer) cell populations. DNA/P85 (but not P85) also increases maturation of local DC (CD11c + CD86(1), CD11c + CD80(1), and CD11c + CD40(1)). We suggest that DNA/P85 promotes the activation and recruitment of the antigen-presenting cells, which further incorporate. express and carry the transgene to the immune system organs. (C) 2008 Elsevier Ltd. All rights reserved.
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