CRISPR perfect adaptation for robust control of cellular immune and apoptotic responses.

ABSTRACT: A central challenge in the quest for precise gene regulation within mammalian cells is the development of regulatory networks that can achieve perfect adaptation-where outputs consistently return to a set baseline post-stimulus. Here, we present such a system that leverages the CRISPR activation (CRISPRa) and anti-CRISPR proteins as two antithetic elements to establish perfect adaptation in mammalian cells and dynamically regulate gene expression. We demonstrate that this system can maintain stable expression levels of target genes in the face of external perturbations, thus providing a robust platform for biological applications. The versatility of our system is further showcased through its integration with endogenous regulatory mechanisms in T cells, such as the NF-κB-mediated immune re

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC11381330 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature