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

Felipe Opazo, Laura Eiden, Line Hansen, Falk Rohrbach, Jesper Wengel, Jørgen Kjems, Günter Mayer

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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.

Original languageEnglish
Article numbere251
JournalMolecular Therapy - Nucleic Acids
Volume4
Number of pages10
ISSN2162-2531
DOIs
Publication statusPublished - 2015

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Nucleotide Aptamers
Quantum Dots
Equipment and Supplies
Clathrin
Endocytosis
Microscopy
Coloring Agents

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Opazo, Felipe ; Eiden, Laura ; Hansen, Line ; Rohrbach, Falk ; Wengel, Jesper ; Kjems, Jørgen ; Mayer, Günter. / Modular Assembly of Cell-targeting Devices Based on an Uncommon G-quadruplex Aptamer. In: Molecular Therapy - Nucleic Acids. 2015 ; Vol. 4.
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Modular Assembly of Cell-targeting Devices Based on an Uncommon G-quadruplex Aptamer. / Opazo, Felipe; Eiden, Laura; Hansen, Line; Rohrbach, Falk; Wengel, Jesper; Kjems, Jørgen; Mayer, Günter.

In: Molecular Therapy - Nucleic Acids, Vol. 4, e251, 2015.

Research output: Contribution to journalJournal articleResearchpeer-review

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AU - Kjems, Jørgen

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AB - 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.

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