Synthetic protein circuits for programmable control of mammalian cell death.
Cell
; 187(11): 2785-2800.e16, 2024 May 23.
Article
em En
| MEDLINE
| ID: mdl-38657604
ABSTRACT
Natural cell death pathways such as apoptosis and pyroptosis play dual roles they eliminate harmful cells and modulate the immune system by dampening or stimulating inflammation. Synthetic protein circuits capable of triggering specific death programs in target cells could similarly remove harmful cells while appropriately modulating immune responses. However, cells actively influence their death modes in response to natural signals, making it challenging to control death modes. Here, we introduce naturally inspired "synpoptosis" circuits that proteolytically regulate engineered executioner proteins and mammalian cell death. These circuits direct cell death modes, respond to combinations of protease inputs, and selectively eliminate target cells. Furthermore, synpoptosis circuits can be transmitted intercellularly, offering a foundation for engineering synthetic killer cells that induce desired death programs in target cells without self-destruction. Together, these results lay the groundwork for programmable control of mammalian cell death.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Morte Celular
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article