A CRISPR-Cas9-Based Near-Infrared Upconversion-Activated DNA Methylation Editing System

• DOI: 10.1021/acsami.0c21223
• Publication Date: 2021-02-03T04:02:58Z
• Authors: Jiadong Chi; Jingzhu Zhao; Songfeng Wei; Yigong Li; Jingtai Zhi; Huijuan Wang; Xiukun Hou; Linfei Hu; Xiangqian Zheng; Ming Gao
• Keywords: 0301 basic medicine; Cell Survival; Infrared Rays; Surface Properties; Plant Biology; DNMT; Mice, Nude; Apoptosis; CIBN; Biochemistry; interspaced palindromic repeats-Cas.; Mice; 03 medical and health sciences; CRISPR-Associated Protein 9; Genetics; DNA methylation editing; 2PHR; Animals; Humans; Particle Size; Molecular Biology; Cells, Cultured; Cancer; Adaptor Proteins, Signal Transducing; Gene Editing; Mice, Inbred BALB C; DNA methylation; NIR; Neoplasms, Experimental; DNA Methylation; CRISPR-Cas 9-Based Near-Infrared Up.; CNAMS; 3A; HEK293 Cells; Genetic Techniques; Female; CRISPR-Cas Systems; fusion proteins; TET

DNA methylation is a kind of crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the status specific genes remains challenging. Here, clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated editing system (CNAMS) was designed for optogenetic methylation. The fusion proteins photosensitive CRY2PHR, catalytic domain DNMT3A or TET1, CIBN catalytically inactive Cas9 (dCas9) were engineered. CNAMS could control in response to blue light, thus allowing spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, spectral sensitivity extended from light (NIR) providing possibility remote editing. These results demonstrated meaningful step forward toward realizing methylation, suggesting wide utility our functional studies on regulation potential therapeutic strategies related diseases.