A general strategy for purification of oligonucleotides synthesized by solid phase synthesis is described. It is based on a recently developed concept involving a bio-orthogonal inverse electron demand Diels-Alder reaction between trans-cyclooctene and tetrazine, termed 'click-to-release'. The strategy has been applied towards the synthesis and purification of a model hairpin RNA strand, as well as a 34 nt long aptamer.