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Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer

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Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer. / Berg, Katharina; Lange, Tobias; Mittelberger, Florian; Schumacher, Udo; Hahn, Ulrich.

In: MOL THER-NUCL ACIDS, Vol. 5, 15.03.2016, p. e294.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Berg, K, Lange, T, Mittelberger, F, Schumacher, U & Hahn, U 2016, 'Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer', MOL THER-NUCL ACIDS, vol. 5, pp. e294. https://doi.org/10.1038/mtna.2016.10

APA

Berg, K., Lange, T., Mittelberger, F., Schumacher, U., & Hahn, U. (2016). Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer. MOL THER-NUCL ACIDS, 5, e294. https://doi.org/10.1038/mtna.2016.10

Vancouver

Berg K, Lange T, Mittelberger F, Schumacher U, Hahn U. Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer. MOL THER-NUCL ACIDS. 2016 Mar 15;5:e294. https://doi.org/10.1038/mtna.2016.10

Bibtex

@article{4f4e73f840884f00bc2b685fe4bcb7cb,
title = "Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer",
abstract = "The heterodimeric laminin receptor α6β4 integrin plays a central role in the promotion of tumor cell growth, invasion, and organotropic metastasis. As an overproduction of the integrin is often linked to a poor prognosis, the inhibition of integrin α6β4 binding to laminin is of high therapeutical interest. Here, we report on the combination of a cell-systematic evolution of ligands by exponential enrichment and a bead-based selection resulting in the first aptamer inhibiting the interaction between α6β4 integrin and laminin-332. This Integrin α6β4-specific DNA Aptamer (IDA) inhibits the adhesion of prostate cancer cells (PC-3) to laminin-332 with an IC50 value of 149 nmol/l. The Kd value concerning the aptamer's interaction with PC-3 cells amounts to 137 nmol/l. Further characterization showed specificity to α6 integrins and a half-life in murine blood plasma of 6 hours. Two truncated versions of the aptamer retained their binding capacity, but lost their ability to inhibit the interaction between laminin-332 and PC-3 cells. Confocal laser scanning microscope studies revealed that the aptamer was internalized into PC-3-cells. Therefore, in addition to the adhesion-blocking function of this aptamer, IDA could also be applied for the delivery of siRNA, microRNA or toxins to cancer cells presenting the integrin α6β4.",
author = "Katharina Berg and Tobias Lange and Florian Mittelberger and Udo Schumacher and Ulrich Hahn",
year = "2016",
month = mar,
day = "15",
doi = "10.1038/mtna.2016.10",
language = "English",
volume = "5",
pages = "e294",
journal = "MOL THER-NUCL ACIDS",
issn = "2162-2531",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer

AU - Berg, Katharina

AU - Lange, Tobias

AU - Mittelberger, Florian

AU - Schumacher, Udo

AU - Hahn, Ulrich

PY - 2016/3/15

Y1 - 2016/3/15

N2 - The heterodimeric laminin receptor α6β4 integrin plays a central role in the promotion of tumor cell growth, invasion, and organotropic metastasis. As an overproduction of the integrin is often linked to a poor prognosis, the inhibition of integrin α6β4 binding to laminin is of high therapeutical interest. Here, we report on the combination of a cell-systematic evolution of ligands by exponential enrichment and a bead-based selection resulting in the first aptamer inhibiting the interaction between α6β4 integrin and laminin-332. This Integrin α6β4-specific DNA Aptamer (IDA) inhibits the adhesion of prostate cancer cells (PC-3) to laminin-332 with an IC50 value of 149 nmol/l. The Kd value concerning the aptamer's interaction with PC-3 cells amounts to 137 nmol/l. Further characterization showed specificity to α6 integrins and a half-life in murine blood plasma of 6 hours. Two truncated versions of the aptamer retained their binding capacity, but lost their ability to inhibit the interaction between laminin-332 and PC-3 cells. Confocal laser scanning microscope studies revealed that the aptamer was internalized into PC-3-cells. Therefore, in addition to the adhesion-blocking function of this aptamer, IDA could also be applied for the delivery of siRNA, microRNA or toxins to cancer cells presenting the integrin α6β4.

AB - The heterodimeric laminin receptor α6β4 integrin plays a central role in the promotion of tumor cell growth, invasion, and organotropic metastasis. As an overproduction of the integrin is often linked to a poor prognosis, the inhibition of integrin α6β4 binding to laminin is of high therapeutical interest. Here, we report on the combination of a cell-systematic evolution of ligands by exponential enrichment and a bead-based selection resulting in the first aptamer inhibiting the interaction between α6β4 integrin and laminin-332. This Integrin α6β4-specific DNA Aptamer (IDA) inhibits the adhesion of prostate cancer cells (PC-3) to laminin-332 with an IC50 value of 149 nmol/l. The Kd value concerning the aptamer's interaction with PC-3 cells amounts to 137 nmol/l. Further characterization showed specificity to α6 integrins and a half-life in murine blood plasma of 6 hours. Two truncated versions of the aptamer retained their binding capacity, but lost their ability to inhibit the interaction between laminin-332 and PC-3 cells. Confocal laser scanning microscope studies revealed that the aptamer was internalized into PC-3-cells. Therefore, in addition to the adhesion-blocking function of this aptamer, IDA could also be applied for the delivery of siRNA, microRNA or toxins to cancer cells presenting the integrin α6β4.

U2 - 10.1038/mtna.2016.10

DO - 10.1038/mtna.2016.10

M3 - SCORING: Journal article

C2 - 26978578

VL - 5

SP - e294

JO - MOL THER-NUCL ACIDS

JF - MOL THER-NUCL ACIDS

SN - 2162-2531

ER -