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A Wireframe DNA Cube: Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E

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DOI

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.

Original languageEnglish
JournalAngewandte Chemie - International Edition
Volume60
Issue40
Pages (from-to)21691-21696
Number of pages6
ISSN1433-7851
DOIs
Publication statusPublished - Sep 2021

    Research areas

  • antibody drug conjugate, atomic force microscopy, controlled DAR, DNA nanotechnology, protein conjugation

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