DNA vaccines have emerged as a potentially important form of vaccination in the control of infectious diseases and cancers. It is now clear that professional antigen-presenting cells (APCs), such as dendritic cells (DCs) play important roles in generating humoral and cell-mediated antigen-specific immune responses by DNA vaccination. Continuing progress in our understanding of how professional APCs uptake DNA, process and present the antigens encoded by DNA vaccines to activate B- and T-cell-mediated immune responses in vaccinated individuals provides a framework from which to design more effective DNA vaccines. Advances in molecular biology technology allow DNA to be easily manipulated and make the implementation of novel DNA vaccine strategies possible. This review discusses strategies employing molecular biology technology to improve DNA vaccine potency. These approaches include strategies to increase the numbers of antigen-expressing DCs, strategies to enhance MHC class I and/or II presentation of the encoded antigen and strategies to prolong the life of antigen-expressing DCs to enhance DNA vaccine potency. We will also discuss the methodology involved in DNA vaccine development targeting human papillomavirus oncogenic protein E7.