Modular design of synthetic receptors for programmed gene regulation in cell therapies

Iowis Zhu, Raymond Liu, Julie M. Garcia, Axel Hyrenius-Wittsten, Dan I. Piraner, Josef Alavi, Divya V. Israni, Bin Liu, Ahmad S. Khalil, Kole T. Roybal

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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 that we call synthetic intramembrane proteolysis receptors (SNIPRs) that have tunable sensing and transcriptional response abilities. We demonstrate the therapeutic potential 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.

Originalspråkengelska
Sidor (från-till)1431-1443.e16
TidskriftCell
Volym185
Nummer8
DOI
StatusPublished - 2022 apr.

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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