Effects of single nucleotide changes on the binding and activity of RNA aptamers to human papillomavirus 16 E7 oncoprotein

A virally-encoded oncoprotein (E7 from human papillomavirus 16, involved in the initiation of cell transformation) was the target for RNA aptamer development by the process of systematic evolution of ligands by exponential enrichment (SELEX). A number of aptamers were identified, one of which was shown to inhibit the interaction between E7 and its major binding partner, pRb. Aptamers with very similar sequences (more than 92% similarity in the random regions) did not share this activity. This study demonstrates the potential of aptamers to be highly specific, with small differences in aptamer sequence having profound effects on function.

Research highlights► Aptamers were selected to HPV16 E7 oncoprotein. ► Aptamers with a similar sequence had different binding affinities for the target protein. ► Aptamers that differed in only one or two nucleotides differed in the ability to disrupt the interaction between GST-E7 and major interaction partner pRb. ► This study demonstrates that small changes in the sequence of RNA aptamers can have large effects on activity. ► This work demonstrates the utility of aptamers as very specific molecular tools.