Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices

被引:1
作者
Liu, Yuxiang [1 ]
Wang, Ruixuan [1 ]
Chen, Qimingxing [1 ]
Chang, Yan [1 ]
Chen, Qi [1 ]
Fukumoto, Kodai [2 ,3 ]
Wang, Bingxun [1 ]
Yu, Jianchen [1 ]
Luo, Changfeng [1 ]
Ma, Jiayuan [1 ]
Chen, Xiaoxia [1 ,4 ]
Murayama, Yuko [3 ]
Umeda, Kenichi [5 ]
Kodera, Noriyuki [5 ]
Harada, Yoshie [2 ]
Sekine, Shun-ichi [3 ]
Li, Jianfeng [1 ,6 ]
Tadakuma, Hisashi [1 ,6 ]
机构
[1] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
[2] Osaka Univ, Inst Prot Res, Osaka 5650871, Japan
[3] RIKEN Ctr Biosyst Dynam Res, Yokohama 2300045, Japan
[4] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Zhejiang Prov Key Lab Pancreat Dis Hangzhou, Hangzhou 310009, Zhejiang, Peoples R China
[5] Kanazawa Univ, Nano Life Sci Inst WPI NanoLSI, Kakuma Machi, Kanazawa 9201192, Japan
[6] ShanghaiTech Univ, Gene Editing Ctr, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
基金
日本科学技术振兴机构; 中国国家自然科学基金; 日本学术振兴会;
关键词
DNA origami; LNP; Cryo-EM; gene expression; NANOSTRUCTURES;
D O I
10.1021/acs.nanolett.4c02104
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.
引用
收藏
页码:8410 / 8417
页数:8
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