Antisense oligonucleotides (ASOs) bind to their cognate mRNA by Watson-Crick base-pairing and modulate its intermediary metabolism to produce a pharmacological effect. Unmodified oligonucleotides are highly polar, poly-anionic macromolecules which have poor drug-like properties. To address these limitations, medicinal chemists have developed chemical modification and conjugation strategies to improve the RNA-binding affinity, metabolic stability and pharmacokinetic properties of therapeutic oligonucleotides. We have used structure based-design to prepare nucleic acid analogs which enhance the drug-like properties of therapeutic oligonucleotides. Recent developments which improve potency and therapeutic efficacy of ASO drugs in animal models will be presented.

Structure guided design of nucleic acid modifications for antisense drug discovery

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.