1. NIR Light-Controlled DNA Nanodevice for Amplified mRNA Imaging and Precise Gene Therapy
- Author
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Miaomiao Xiang, Yuelin Jiang, jiajia zhou, Guochen Bao, Xianzhu Luo, Le Zhang, Dayong Jin, Yuezhong Xian, and Cuiling Zhang
- Abstract
Accurately delivering antisense oligonucleotides (ASOs) to tumor cells for gene therapy poses a significant challenge. To address this issue, we develop a NIR light-activable DNA nanodevice to target survivin mRNA and simultaneously release ASOs in tumor cells, which allows high-precision spatiotemporal imaging with high sensitivity and efficient gene therapy. The concept is based on upconversion nanoparticles, which can convert NIR light into UV emissions to activate an entropy-driven DNA walking system that further determines mRNA in tumor cells. The intramolecular toehold-mediated entropy-driven catalytic reaction generates a large amount of Bcl-2 ASOs, which allows accurate delivery of ASOs for gene therapy due to the specific targeting of mRNA in tumor cells. Both in vitro and in vivo results show that the NIR light induced-DNA nanodevice can detect mRNA with high sensitivity by DNA walking amplification system and high precision in gene delivery. Moreover, the released ASOs from DNA walking system deregulate the expression of Bcl-2 anti-apoptosis protein and induce tumor cell apoptosis, thereby suppressing tumor growth without a transfection reagent. The NIR-light-controlled DNA nanodevice holds great potential for precise gene therapy in clinical applications.
- Published
- 2023