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A comparative analysis of cell surface targeting aptamers

Author

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  • Linsley Kelly

    (Albert Einstein College of Medicine
    Duke University School of Medicine)

  • Keith E. Maier

    (Albert Einstein College of Medicine
    EpiCypher Inc)

  • Amy Yan

    (Albert Einstein College of Medicine
    Duke University School of Medicine)

  • Matthew Levy

    (Albert Einstein College of Medicine
    Creyon Bio, Inc.)

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.

Suggested Citation

  • Linsley Kelly & Keith E. Maier & Amy Yan & Matthew Levy, 2021. "A comparative analysis of cell surface targeting aptamers," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26463-w
    DOI: 10.1038/s41467-021-26463-w
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    1. Fernando Pastor & Despina Kolonias & Paloma H. Giangrande & Eli Gilboa, 2010. "Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay," Nature, Nature, vol. 465(7295), pages 227-230, May.
    2. Andrew Bradbury & Andreas Plückthun, 2015. "Reproducibility: Standardize antibodies used in research," Nature, Nature, vol. 518(7537), pages 27-29, February.
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    Cited by:

    1. Arnaud Desrosiers & Rabeb Mouna Derbali & Sami Hassine & Jérémie Berdugo & Valérie Long & Dominic Lauzon & Vincent De Guire & Céline Fiset & Luc DesGroseillers & Jeanne Leblond Chain & Alexis Vallée-B, 2022. "Programmable self-regulated molecular buffers for precise sustained drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Xijiao Ren & Rui Xue & Yan Luo & Shuang Wang & Xinyue Ge & Xuemei Yao & Liqi Li & Junxia Min & Menghuan Li & Zhong Luo & Fudi Wang, 2024. "Programmable melanoma-targeted radio-immunotherapy via fusogenic liposomes functionalized with multivariate-gated aptamer assemblies," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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