Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide

Successful gene therapy depends on the development of efficient delivery systems. Although pDNA and ODN are novel candidates for nonviral gene therapy, their clinical applications are generally limited owing to their rapid degradation by nucleases in serum and rapid clearance. A great deal of effort had been devoted to developing gene delivery systems, including physical methods and carrier-mediated methods. Both methods could improve transfection efficacy and achieve high gene expression in vitro and in vivo. As for carrier-mediated delivery in vivo, since gene expression depends on the particle size, charge ratio, and interaction with blood components, these factors must be optimized. Furthermore, a lack of cell-selectivity limits the wide application to gene therapy; therefore, the use of ligand-modified carriers is a promising strategy to achieve well-controlled gene expression in target cells. In this review, we will focus on the in vivo targeted delivery of pDNA and ODN using nonviral carriers. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:726-745, 2008