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Proper targeting of DNA vaccines has been identified as a crucial factor in improving the efficacy of DNA vaccines. In general, targeting measures affect either directly the DNA or the protein(s) expressed by DNA vaccines toward antigen-presenting cells (APC) to enable efficacious antigen presentation via MHC class I and II pathways. Improved targeting of the delivery of antigen can significantly increase the protective effects and reduce vaccination doses and toxicity. In this review, we summarize the targeting approaches reported in the scientific literature to improve DNA vaccine efficacy.