Modular Assembly of Cell-targeting Devices Based on an Uncommon G-quadruplex Aptamer

Molecular Therapy. Nucleic Acids
Felipe OpazoGünter Mayer

Abstract

Aptamers are valuable tools that provide great potential to develop cost-effective diagnostics and therapies in the biomedical field. Here, we report a novel DNA aptamer that folds into an unconventional G-quadruplex structure able to recognize and enter specifically into human Burkitt's lymphoma cells. We further optimized this aptamer to a highly versatile and stable minimized version. The minimized aptamer can be easily equipped with different functionalities like quantum dots, organic dyes, or even a second different aptamer domain yielding a bi-paratopic aptamer. Although the target molecule of the aptamer remains unknown, our microscopy and pharmacological studies revealed that the aptamer hijacks the clathrin-mediated endocytosis pathway for its cellular internalization. We conclude that this novel class of aptamers can be used as a modular tool to specifically deliver different cargoes into malignant cells. This work provides a thorough characterization of the aptamer and we expect that our strategy will pave the path for future therapeutic applications.

References

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Citations

Dec 1, 2015·Methods : a Companion to Methods in Enzymology·Laia CivitGünter Mayer
Nov 30, 2016·Angewandte Chemie·Patrick SeyfriedAlexander Heckel
Mar 6, 2019·Nucleic Acid Therapeutics·Kazuaki HoshiKazunori Ikebukuro
May 3, 2019·Angewandte Chemie·Günter MayerFranziska Pfeiffer
Nov 6, 2018·Genes·Carla Lucia EspositoVittorio de Franciscis
Jun 8, 2021·Chemical Science·Olga PlückthunGünter Mayer
Aug 18, 2021·ACS Applied Materials & Interfaces·Morgan ChandlerKirill A Afonin

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Methods Mentioned

BETA
circular dicroism
flow cytometry
ion
atomic force microscopy
fluorescence
AFM

Software Mentioned

GraphPad Prism
GraphPad
Matlab

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