Abstract
Attaining the full therapeutic utility of antisense and siRNA oligonucleotides will require understanding of the biological barriers that stand between initial administration of these drugs and their final actions within cells. This review examines some of the key barriers that affect the biodistribution of oligonucleotides both in molecular form and when they are associated with nanocarriers. An understanding of the biological processes underlying these barriers will aid in the design of more effective delivery systems.