Poly-β amino ester-containing microparticles enhance the activity of nonviral genetic vaccines

Steven R. Little, David M. Lynn, Qing Ge, Daniel G. Anderson, Sidharth V. Puram, Jianzhu Chen, Herman N. Eisen, Robert Langer

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

Abstract

Current nonviral genetic vaccine systems are less effective than viral vaccines, particularly in cancer systems where epitopes can be weakly immunogenic and antigen-presenting cell processing and presentation to T cells is down-regulated. A promising nonviral delivery method for genetic vaccines involves microencapsulation of antigen-encoding DNA, because such particles protect plasmid payloads and target them to phagocytic antigen-presenting cells. However, conventional microparticle formulations composed of poly lactic-co-glycolic acid take too long to release encapsulated payload and fail to induce high levels of target gene expression. Here, we describe a microparticle-based DNA delivery system composed of a degradable, pH-sensitive poly-β amino ester and poly lactic-co-glycolic acid. These formulations generate an increase of 3-5 orders of magnitude in transfection efficiency and are potent activators of dendritic cells in vitro. When used as vaccines in vivo, these microparticle formulations, unlike conventional formulations, induce antigen-specific rejection of transplanted syngenic tumor cells.

Original languageEnglish
Pages (from-to)9534-9539
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number26
DOIs
StatePublished - Jun 29 2004

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