Chemical modifications to improve the cellular uptake of oligonucleotides.

Specific control of gene expression by synthetic oligonucleotides (ON) is now widely used for target validation but clinical applications are limited by ON bioavailability. Moreover, most currently used strategies for physical and chemical delivery cannot be easily implemented in vivo. This article reviews new strategies which appear promising for ON delivery. The first part deals with ON chemical modifications aiming at improving cellular uptake as for instance the grafting of cationic groups on the ON backbone. The second part concerns ON conjugation to cell penetrating peptides.