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Synthetic Artificial Apoptosis-Inducing Receptor for On-Demand Deactivation of Engineered Cells

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DOI

The design of a fully synthetic, chemical “apoptosis-inducing receptor” (AIR) molecule is reported that is anchored into the lipid bilayer of cells, is activated by the incoming biological input, and responds with the release of a secondary messenger—a highly potent toxin for cell killing. The AIR molecule has four elements, namely, an exofacial trigger group, a bilayer anchor, a toxin as a secondary messenger, and a self-immolative scaffold as a mechanism for signal transduction. Receptor installation into cells is established via a robust protocol with minimal cell handling. The synthetic receptor remains dormant in the engineered cells, but is effectively triggered externally by the addition of an activating biomolecule (enzyme) or in a mixed cell population through interaction with the surrounding cells. In 3D cell culture (spheroids), receptor activation is accessible for at least 5 days, which compares favorably with other state of the art receptor designs.

Original languageEnglish
Article number2004432
JournalAdvanced Science
Volume8
Issue13
ISSN2198-3844
DOIs
Publication statusPublished - Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

    Research areas

  • artificial receptors, glucuronide, prodrugs, self-immolative linkers, signal transduction

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