Near-infrared upconversion-activated CRISPR-Cas9 system: A remote-controlled gene editing platform.
Yongchun PanJingjing YangXiaowei LuanXinli LiuXueqing LiJian YangTing HuangLu SunYuzhen WangYouhui LinYujun SongPublished in: Science advances (2019)
As an RNA-guided nuclease, CRISPR-Cas9 offers facile and promising solutions to mediate genome modification with respect to versatility and high precision. However, spatiotemporal manipulation of CRISPR-Cas9 delivery remains a daunting challenge for robust effectuation of gene editing both in vitro and in vivo. Here, we designed a near-infrared (NIR) light-responsive nanocarrier of CRISPR-Cas9 for cancer therapeutics based on upconversion nanoparticles (UCNPs). The UCNPs served as "nanotransducers" that can convert NIR light (980 nm) into local ultraviolet light for the cleavage of photosensitive molecules, thereby resulting in on-demand release of CRISPR-Cas9. In addition, by preparing a single guide RNA targeting a tumor gene (polo-like kinase-1), our strategies have successfully inhibited the proliferation of tumor cell via NIR light-activated gene editing both in vitro and in vivo. Overall, this exogenously controlled method presents enormous potential for targeted gene editing in deep tissues and treatment of a myriad of diseases.
Keyphrases
- crispr cas
- genome editing
- photodynamic therapy
- cancer therapy
- fluorescence imaging
- drug delivery
- drug release
- fluorescent probe
- gene expression
- genome wide
- small molecule
- signaling pathway
- cell therapy
- single cell
- squamous cell carcinoma
- copy number
- dna binding
- papillary thyroid
- stem cells
- dna methylation
- high throughput
- mesenchymal stem cells
- lymph node metastasis
- quantum dots
- young adults
- squamous cell
- highly efficient
- climate change
- combination therapy
- protein kinase
- transcription factor
- genome wide identification