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

TY - JOUR

T1 - Modular Assembly of Cell-targeting Devices Based on an Uncommon G-quadruplex Aptamer

AU - Opazo, Felipe

AU - Eiden, Laura

AU - Hansen, Line

AU - Rohrbach, Falk

AU - Wengel, Jesper

AU - Kjems, Jørgen

AU - Mayer, Günter

PY - 2015

Y1 - 2015

N2 - 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.

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.

KW - LOCKED NUCLEIC-ACIDS

KW - SIRNA CHIMERAS

KW - CANCER-THERAPY

KW - DRUG-DELIVERY

KW - IN-VITRO

KW - INHIBITOR

KW - CHEMOTHERAPY

KW - ENDOCYTOSIS

KW - TRANSFERRIN

KW - PROTEINS

U2 - 10.1038/mtna.2015.25

DO - 10.1038/mtna.2015.25

M3 - Journal article

C2 - 26325628

SN - 2162-2531

VL - 4

JO - Molecular Therapy - Nucleic Acids

JF - Molecular Therapy - Nucleic Acids

M1 - e251

ER -