Systematic Review of Aptamer Sequence Reporting in the Literature Reveals Widespread Unexplained Sequence Alterations

Aptamers have been the subject of more than 144,000 papers to date. However, there has been a growing concern that errors in reporting aptamer research limit the reliability of these reagents for research and other applications. These observations noting inconsistencies in the use of our RNA anti-lysozyme aptamer served as an impetus for our systematic review of the reporting of aptamer sequences in the literature. Our detailed examination of literature citing the RNA anti-lysozyme aptamer revealed that 93% of the 61 publications reviewed reported unexplained altered sequences with 86% of those using DNA variants. The ten most cited aptamers were examined using a standardized methodology in order to categorize the extent to which the sequences themselves were apparently improperly reproduced, both in the literature and presumably in experiments beyond their discovery. Our review of 800 aptamer publications spanned decades, multiple journals, and research groups, and revealed that 44% of the papers reported unexplained sequence alterations. We identified ten common categories of sequence alterations including deletions, substitutions, additions, among others. The robust data set we have produced elucidates a source of irreproducibility and unreliability in our field and can be used as a starting point for building evidence-based best practices in publication standards to elevate the rigor and reproducibility of aptamer research.