Engineering Cellular Signal Sensors based on CRISPR-sgRNA Reconstruction Approaches

Zhan, Hengji; Xiao, Lulu; Li, Aolin; Yao, Lin; Cai, Zhiming; Liu, Yuchen

doi:10.7150/ijbs.42299

Cited by 1 publication

(1 citation statement)

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“…Synthetic RNA-based switch is an increasingly common application in synthetic biology to engineer cell function, which involves incorporating aptamer domains that can sense small molecules into the regulation of gene expression of interest [ 5 ]. Aptamers show a number of advantages over traditional protein-based transcription controllers [ 6 ]. Although proper function of RNA switches depends on a large extent on optimal connections between aptamers and catalytic cores, regulatory modifications of expressed genes by these switches occupy little space of the genome.…”

Section: Introductionmentioning

confidence: 99%

CRISPR-based gene expression platform for precise regulation of bladder cancer

Zhan,

Li,

Liu

et al. 2024

Cell Mol Biol Lett

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The development of compact CRISPR systems has facilitated delivery but has concurrently reduced gene editing efficiency, thereby limiting the further utilization of CRISPR systems. Enhancing the efficiency of CRISPR systems poses a challenging task and holds significant implications for the advancement of biotechnology. In our work, we report a synthetic dual-antibody system that can stably exist in the intracellular environment, specifically inhibiting the functions of NF-κB and β-catenin. This not only elevates the transgenic expression of the CRISPR system by suppressing the innate immune response within cells to enhance the gene editing efficiency but also demonstrates a notable tumor inhibitory effect. Based on the specific output expression regulation of CRISPR-CasΦ, we constructed a CRISPR-based gene expression platform, which includes sensor modules for detecting intracellular β-catenin and NF-κB, as well as an SDA module to enhance overall efficiency. In vitro experiments revealed that the CRISPR-based gene expression platform exhibited superior CDK5 expression inhibition efficiency and specific cytotoxicity towards tumor cells. In vitro experiments, we found that CRISPR-based gene expression platforms can selectively kill bladder cancer cells through T cell-mediated cytotoxicity. Our design holds significant assistant potential of transgene therapy and may offer the capability to treat other diseases requiring transgene therapy.

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Section: Introductionmentioning

confidence: 99%