chapter  17
20 Pages

Optimization of Second-Generation Antisense Drugs: Going Beyond Generation 2.0

WithBrett P. Monia, Rosie Z. Yu, Walt Lima, Andrew Siwkowski

This chapter will summarize recent progress in the optimization of oligonucleotide design to increase antisense potency in animals by maximizing RNase H activity for oligonucleotides that contain chemical modifications that do not support RNase H activity, but yet offer other benefits for antisense drug technology. Readers are directed to other chapters in this volume to review recent progress in the medicinal chemistry of oligonucleotides that act through siRNA pathways.