Chemically modified nucleic acids (CNAs ) are widely explored as antisense oligonucleotide (AON) or small interfering RNA (siRNA) candidates for therapeutic applications. Research over the last 20 years has led to an improved understanding of how modification affects structure, stabiity and activity of CNAs, with key insights ranging from conformational changes as a consequence of chemical modification to the modulation of RNA affinity by stereoelectronic effects and hydration. Although crystal structures have only been determined for a subset of the large number of modifications that were synthesized and analyzed in the AON and siRNA contexts to date, they have yielded guiding principles for the design of new CNAs with tailor-made properties, including pairing specificity, nuclease resistance, and cellular uptake. The presentation will cover recent results regarding the structure and activity of selected CNAs.Supported by the US NIH (R01 GM055237, R01 GM071461).Reference:Egli, M.; Pallan, P.S. Crystallographic studies of chemically modified nucleic acids: a backward glance. Chem. Biodiv. 2010, 7:60-89.

Structure/function studies of chemically modified antisense and siRNA oligonucleotides

243rd National Meeting (2012)

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