Article abstract
Nature Materials 3, 190 - 196 (2004)
Published online: 15 February 2004 | doi:10.1038/nmat1075
Subject Categories: Polymers | Biomedical materials
Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines
Chun Wang1, Qing Ge2, David Ting1,4, David Nguyen1,4, Hui-Rong Shen3, Jianzhu Chen2, Herman N. Eisen2, Jorge Heller3, Robert Langer1 & David Putnam1,5
Abstract
Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.
- Department of Chemical Engineering, E25-342, 77 Mass. Ave., Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- AP Pharma, Inc., 123 Saginaw Drive, Redwood City, California 94063, USA
- Present address: Harvard-MIT Division of Health Sciences and Technology, E25-519, 77 Mass. Ave., Cambridge, Massachusetts 02139, USA
- Present address: School of Chemical and Biomolecular Engineering and the Biomedical Engineering Program, 270 Olin Hall, Cornell University, Ithaca, New York 14853, USA
Correspondence to: Jorge Heller3 e-mail: jorgeheller2@aol.com
Correspondence to: Robert Langer1 e-mail: rlanger@mit.edu
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