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A Wireframe DNA Cube: Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E
Author(s) -
Märcher Anders,
Nijenhuis Minke A. D.,
Gothelf Kurt V.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202107221
Subject(s) - conjugate , antibody drug conjugate , dna , drug delivery , antibody , cube (algebra) , chemistry , combinatorial chemistry , nanotechnology , microbiology and biotechnology , materials science , monoclonal antibody , mathematics , medicine , biochemistry , biology , immunology , mathematical analysis , combinatorics
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.