Linking viscosity to higher-order interactions of chemically modified double-stranded oligonucleotides

Jonathan Booth – Principal Scientist, AstraZeneca; Kevin Treacher – Principal Scientist, AstraZeneca; Snow Stolnik – Professor of Pharmaceutics, University of Nottingham; Mischa Zelzer – Associate Professor of Pharmacy, University of Nottingham

Introduction:

The viscosity of oligonucleotides in solution can exhibit unpredictable behaviour, posing significant challenges for both manufacturing and patient administration. [1] Therapeutic oligonucleotides are often chemically modified to achieve nuclease resistance and optimise pharmacokinetic properties [2]. To our knowledge, the impact of such modifications on viscosity has not yet been investigated. This study examines whether chemical modifications of oligonucleotides alter molecular interactions, potentially leading to increased viscosity.