Faculty of Natural Sciences

TY - JOUR

T1 - A Wireframe DNA Cube

T2 - Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E

AU - Märcher, Anders

AU - Nijenhuis, Minke A.D.

AU - Gothelf, Kurt V.

PY - 2021/9

Y1 - 2021/9

N2 - In recent years, several antibody drug conjugates (ADC) have been accepted by the FDA as therapeutics against cancer. It is well-known that control of drug-to-antibody ratio (DAR) is vital for the success of an ADC, which inspires the advancement of better and simpler methods for tight control of DAR. We present the development of an antibody DNA wireframe cube conjugate for precise control of DAR. The DNA wireframe cube consists of four single strands, which when folded present eight single stranded domains. One domain is bound to a monofunctionalized antibody DNA conjugate, and the seven others are attached to DNA functionalized with the potent tubulin inhibitor MMAE, thereby preparing an ADC with a DAR of precisely seven. The formation of the ADC is investigated by gel electrophoresis and atomic force microscopy. Lastly, the developed MMAE loaded ADC was used for targeted drug delivery in vitro.

AB - In recent years, several antibody drug conjugates (ADC) have been accepted by the FDA as therapeutics against cancer. It is well-known that control of drug-to-antibody ratio (DAR) is vital for the success of an ADC, which inspires the advancement of better and simpler methods for tight control of DAR. We present the development of an antibody DNA wireframe cube conjugate for precise control of DAR. The DNA wireframe cube consists of four single strands, which when folded present eight single stranded domains. One domain is bound to a monofunctionalized antibody DNA conjugate, and the seven others are attached to DNA functionalized with the potent tubulin inhibitor MMAE, thereby preparing an ADC with a DAR of precisely seven. The formation of the ADC is investigated by gel electrophoresis and atomic force microscopy. Lastly, the developed MMAE loaded ADC was used for targeted drug delivery in vitro.

KW - antibody drug conjugate

KW - atomic force microscopy

KW - controlled DAR

KW - DNA nanotechnology

KW - protein conjugation

UR - http://www.scopus.com/inward/record.url?scp=85113978260&partnerID=8YFLogxK

U2 - 10.1002/anie.202107221

DO - 10.1002/anie.202107221

M3 - Journal article

C2 - 34309988

AN - SCOPUS:85113978260

VL - 60

SP - 21691

EP - 21696

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

SN - 1433-7851

IS - 40

ER -