CRISPR-based gene expression platform for precise regulation of bladder cancer.
Bladder cancer
CRISPR system
Gene regulation tool
Gene therapy
Transgene
Journal
Cellular & molecular biology letters
ISSN: 1689-1392
Titre abrégé: Cell Mol Biol Lett
Pays: England
ID NLM: 9607427
Informations de publication
Date de publication:
09 May 2024
09 May 2024
Historique:
received:
28
01
2024
accepted:
27
03
2024
medline:
10
5
2024
pubmed:
10
5
2024
entrez:
9
5
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38724931
doi: 10.1186/s11658-024-00569-7
pii: 10.1186/s11658-024-00569-7
doi:
Substances chimiques
beta Catenin
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
66Informations de copyright
© 2024. The Author(s).
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