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


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-beta 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.

SUBMITTER: Little SR 

PROVIDER: S-EPMC470709 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

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

Little Steven R SR   Lynn David M DM   Ge Qing Q   Anderson Daniel G DG   Puram Sidharth V SV   Chen Jianzhu J   Eisen Herman N HN   Langer Robert R  

Proceedings of the National Academy of Sciences of the United States of America 20040621 26


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 formulatio  ...[more]

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