A bioorthogonal antibody-based chemically-induced-dimerization switch for therapeutic application

Martinko, A. J.; Tran, H. L.; Simonds, E. F.; Cooke, A. L.; Huang, Z.; Raguveer, S.; Agullet, J. P.; Prasad, S.; Going, C.; Marshall, L.; Park, T.; Banerjee, S.; Macdonald, R.; Jian, M.; Ng, K.; Palakodaty, A.; Kaur, M.; Ponce, A.; Tabrizi, M.; Hill, Z. B.

doi:10.1101/2023.04.11.536272

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bioRxiv · 10.1101/2023.04.11.536272

A bioorthogonal antibody-based chemically-induced-dimerization switch for therapeutic application

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Abstract

We present the Indinavir Ligand Induced Transient Engagement switch (IDV LITE Switch), a fully synthetic Chemically Induced Dimerization (CID) system wherein two humanized antibody fragments are heterodimerized by the antiviral drug indinavir. The IDV LITE Switch represents the first CID system made from fully humanized protein components and dimerized by a clinically approved small molecule drug lacking a mammalian target, making it an ideal bioorthogonal molecular switch for application in small-molecule controlled therapeutics.

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Martinko, A. J., Tran, H. L., Simonds, E. F., Cooke, A. L., Huang, Z., Raguveer, S., Agullet, J. P., Prasad, S., Going, C., Marshall, L., Park, T., Banerjee, S., Macdonald, R., Jian, M., Ng, K., Palakodaty, A., Kaur, M., Ponce, A., Tabrizi, M., Hill, Z. B.. 2023-04-11. A bioorthogonal antibody-based chemically-induced-dimerization switch for therapeutic application. https://doi.org/10.1101/2023.04.11.536272

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