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A DNA Origami-Based Gene Editing System for Efficient Gene Therapy in Vivo |
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| Authors: | Wantao Tang Ting Tong Hong Wang Xuehe Lu Changping Yang Yushuai Wu Yuang Wang Prof Jianbing Liu Prof Baoquan Ding |
| Institution: | 1. School of Materials Science and Engineering, Zhengzhou University, Zhengzhou, 450001 China
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, 100190 China;2. CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, 100190 China;3. CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, 100190 China University of Chinese Academy of Sciences, Beijing, 100049 China;4. School of Materials Science and Engineering, Zhengzhou University, Zhengzhou, 450001 China |
| Abstract: | DNA nanostructures have played an important role in the development of novel drug delivery systems. Herein, we report a DNA origami-based CRISPR/Cas9 gene editing system for efficient gene therapy in vivo. In our design, a PAM-rich region precisely organized on the surface of DNA origami can easily recruit and load sgRNA/Cas9 complex by PAM-guided assembly and pre-designed DNA/RNA hybridization. After loading the sgRNA/Cas9 complex, the DNA origami can be further rolled up by the locking strands with a disulfide bond. With the incorporation of DNA aptamer and influenza hemagglutinin (HA) peptide, the cargo-loaded DNA origami can realize the targeted delivery and effective endosomal escape. After reduction by GSH, the opened DNA origami can release the sgRNA/Cas9 complex by RNase H cleavage to achieve a pronounced gene editing of a tumor-associated gene for gene therapy in vivo. This rationally developed DNA origami-based gene editing system presents a new avenue for the development of gene therapy. |
| Keywords: | DNA Origami Drug Delivery Gene Editing Gene Therapy Self-Assembly |