A comparative analysis of cell surface targeting aptamers

Linsley Kelly, Keith E. Maier, Amy Yan and Matthew Levy ()
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Linsley Kelly: Albert Einstein College of Medicine
Keith E. Maier: Albert Einstein College of Medicine
Amy Yan: Albert Einstein College of Medicine
Matthew Levy: Albert Einstein College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Aptamers represent a potentially important class of ligands for the development of diagnostics and therapeutics. However, it is often difficult to compare the function and specificity of many of these molecules as assay formats and conditions vary greatly. Here, with an interest in developing aptamer targeted therapeutics that could effectively deliver cargoes to cells, we chemically synthesize 15 aptamers that have been reported to target cell surface receptors or cells. Using standardized assay conditions, we assess each aptamer’s binding properties on a panel of 11 different cancer cell lines, correlate aptamer binding to antibody controls and use siRNA transfection to validate each aptamer’s binding to reported target receptors. Using a subset of these molecules known to be expressed on prostate cancers, we use near-infrared in vivo imaging to assess the tumor localization following intravenous injection. Our data demonstrate some surprising differences in the reported specificity and function for many of these molecules and raise concerns regarding their cell targeting capabilities. They also identify an anti-human transferrin aptamer, Waz, as a robust candidate for targeting prostate cancers and for future development of aptamer-based therapeutics.

Date: 2021
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DOI: 10.1038/s41467-021-26463-w

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