Precise Synergistic Photoregulation of Dual-Target Gene Expression by Engineering Caged Two-in-One DNA-RNA...

Area of Science:

• Biotechnology
• Molecular Biology
• Nanotechnology

Background:

• Precise spatiotemporal control of gene expression is crucial for understanding gene function and biological processes.
• Developing advanced tools for targeted gene regulation is essential for therapeutic applications.

Purpose of the Study:

• To design and develop an engineering caged two-in-one DNA-RNA nanoframework for synergistic photoregulation of dual-target tumor gene expression.
• To investigate the potential of this nanoframework for combinatorial RNA interference (RNAi)-based cancer therapy.

Main Methods:

• Fabrication of a DNA-RNA nanoframework incorporating near-infrared (NIR) responsive divalent siRNAs.
• Utilizing in-situ generated reactive oxygen species (ROS) triggered by NIR light to release siRNAs.
• Evaluating the spatiotemporal control of gene silencing in living tumor cells and in vivo antitumor effects.

Main Results:

• The caged nanoframework demonstrated light-triggered release of dual-target siRNAs, enabling temporary inhibition of RNAi activity without NIR irradiation.
• NIR light irradiation precisely regulated dual-target gene expression (CENPF and FOXM1) and associated signaling pathways (PI3K, MAPK), leading to synergistic anti-tumor effects.
• The system achieved simultaneous photoregulation of dual-target RNAi in living tumor cells and demonstrated in vivo NIR-responsive antitumor effects.

Conclusions:

• The engineered caged two-in-one DNA-RNA nanoframework offers a promising tool for spatiotemporal control of gene expression.
• This platform provides a novel strategy for exploring gene regulatory networks and developing divalent siRNA-based precise therapies for cancer.