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, Jahrgang 5, 15.03.2016, S. e294.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -