Affiliation:
1. School of Materials Science and Engineering Zhengzhou University Zhengzhou 450001 China
2. CAS Key Laboratory of Nanosystem and Hierarchical Fabrication National Center for Nanoscience and Technology Beijing 100190 China
3. University of Chinese Academy of Sciences Beijing 100049 China
Abstract
AbstractDNA 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.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Youth Innovation Promotion Association of the Chinese Academy of Sciences
Subject
General Chemistry,Catalysis
Cited by
12 articles.
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