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

Area of Science:

• Biotechnology
• Molecular Biology
• Gene Editing

Background:

• Compact CRISPR systems offer improved delivery but reduced gene editing efficiency, limiting applications.
• Enhancing CRISPR efficiency is crucial for advancing biotechnology and therapeutic interventions.

Purpose of the Study:

• To develop a synthetic dual-antibody system to enhance CRISPR gene editing efficiency.
• To create a CRISPR-based gene expression platform for targeted gene regulation and cancer therapy.

Main Methods:

• Constructed a synthetic dual-antibody system to inhibit intracellular NF-κB and β-catenin.
• Developed a CRISPR-based gene expression platform with sensor modules for NF-κB and β-catenin, and an SDA module.
• Evaluated the system's efficiency in inhibiting CDK5 expression and its cytotoxicity in vitro.

Main Results:

• The dual-antibody system stably inhibited NF-κB and β-catenin intracellularly.
• The CRISPR-based platform enhanced transgenic expression and gene editing efficiency by suppressing innate immune responses.
• Demonstrated superior CDK5 expression inhibition and specific cytotoxicity towards tumor cells, including selective killing of bladder cancer cells via T cell-mediated cytotoxicity.

Conclusions:

• The developed system significantly enhances CRISPR gene editing efficiency and demonstrates anti-tumor effects.
• The CRISPR-based gene expression platform shows potential for transgene therapy and treating diseases requiring gene modulation.
• This approach offers a promising strategy for advancing gene therapy and cancer treatment modalities.