State of the art and perspectives for the delivery of antisense oligonucleotides and siRNA by polymeric nanocarriers

Knocking down gene expression using either antisense oligonucleotides (AS-ODNs) or small interfering RNA (siRNAs) has raised a lot of interest in designing new pathways for therapeutics. Despite their potentialities, these negatively charged and hydrophilic molecules request chemical modifications or a carrier that allows cell recognition, cell internalization and moreover subcellular penetration. Although chemical modifications were brought to the basic AS-ODNs and siRNAs, their sensitivity to degradation and poor intracellular penetration is still hampering their clinical applications. We present here the potentialities of polymeric carriers or the use of alternative administration route such as oral, ocular and skin delivery to improve their delivery and to circumvent the hurdles for their clinical applications. (c) 2008 Elsevier B.V. All rights reserved.