CRISPR/RNA Aptamer System Activated by an AND Logic Gate for Biomarker-Driven Theranostics

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Engineered RNA devices are crucial for detecting biomarkers and enabling responsive therapies.
• Current theranostic platforms require advancement for integrated diagnosis and treatment.
• Targeting specific microRNAs (miRNAs) shows promise in cancer therapy.

Purpose of the Study:

• To develop an integrated nano CRISPR Cas13a/RNA aptamer theranostic platform (InCasApt).
• To achieve simultaneous biomarker detection and biomarker-driven therapy.
• To investigate the efficacy of InCasApt in targeting carcinogenic miRNAs in tumor cells.

Main Methods:

• Coloading Cas13a/crRNA complex, hairpin reporter, Ce6 photosensitizer, and aptamer precursor onto dendritic mesoporous silicon nanoparticles (DMSN).
• Utilizing an AND logic gate mechanism activated by elevated miRNA-155 and miRNA-21 expression in tumor cells.
• Employing fluorescence for disease evaluation and reactive oxygen species (ROS) generation for photodynamic therapy.

Main Results:

• InCasApt demonstrated inertness in normal cells and activation in tumor cells with high miRNA-155 and miRNA-21 levels.
• The platform successfully generated fluorescence for disease detection and ROS for photodynamic therapy.
• InCasApt upregulated the antioncogene BRG1 and suppressed tumor migration by inhibiting target miRNAs.

Conclusions:

• InCasApt serves as a versatile miRNA-targeting strategy for integrated cancer diagnosis and therapy.
• The platform effectively bridges the gap between disease detection and therapeutic intervention.
• This engineered RNA device offers a novel approach for theranostic applications in oncology.