A DNA Origami‐Based Gene Editing System for Efficient Gene Therapy in Vivo

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...

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Bibliographic Details
Published inAngewandte Chemie Vol. 135; no. 51
Main Authors Tang, Wantao, Tong, Ting, Wang, Hong, Lu, Xuehe, Yang, Changping, Wu, Yushuai, Wang, Yuang, Liu, Jianbing, Ding, Baoquan
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 18.12.2023
Subjects
Aptamers
Chemistry
CRISPR
Deoxyribonucleic acid
DNA
DNA Origami
Drug Delivery
Drug delivery systems
Editing
Gene Editing
Gene Therapy
Genetic engineering
Genetic modification
Hemagglutinins
Hybridization
Ribonuclease H
Self-Assembly
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Summary: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. DNA nanostructures have been widely developed as the smart drug delivery systems. Herein, a DNA origami with precisely organized PAM‐rich region on its surface has been constructed to efficiently recruit and load sgRNA/Cas9 complex by PAM‐guided assembly and pre‐designed DNA/RNA hybridization for targeted gene editing of tumor‐associated gene. This DNA origami‐based gene editing system has achieved a pronounced gene therapy in vivo.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202315093