Design and modular assembly of synthetic intramembrane proteolysis receptors for custom gene regulation in therapeutic cells
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Published version
Date
2021-05-21
Authors
Zhu, Iowis
Liu, Raymond
Hyrenius-Wittsten, Axel
Piraner, Dan I.
Alavi, Josef
Israni, Divya V.
Khalil, Ahmad S.
Roybal, Kole T.
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Published version
OA Version
Citation
I. Zhu, R. Liu, A. Hyrenius-Wittsten, D. Piraner, J. Alavi, D. Israni, A. Khalil, K. Roybal. 2021. "Design and modular assembly of synthetic intramembrane proteolysis receptors for custom gene regulation in therapeutic cells." https://doi.org/10.1101/2021.05.21.445218
Abstract
[Synthetic biology has established powerful tools to precisely control cell function. Engineering these systems to meet clinical requirements has enormous medical implications. Here, we adopted a clinically driven design process to build receptors for the autonomous control of therapeutic cells. We examined the function of key domains involved in regulated intramembrane proteolysis and showed that systematic modular engineering can generate a class of receptors we call SyNthetic Intramembrane Proteolysis Receptors (SNIPRs) that have tunable sensing and transcriptional response abilities. We demonstrate the potential transformative utility of the receptor platform by engineering human primary T cells for multi-antigen recognition and production of dosed, bioactive payloads relevant to the treatment of disease. Our design framework enables the development of fully humanized and customizable transcriptional receptors for the programming of therapeutic cells suitable for clinical translation.]
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Copyright the Author(s). This preprint is made available under a CC-BY-NC-ND 4.0 International license.