DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy

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Chen , Z , Zhang , F , Zhang , H , Cheng , L , Chen , K , Shen , J , Qi , J , Deng , L , He , C , Santos , H A & Cui , W 2021 , ' DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy ' , Advanced Science , vol. 8 , no. 9 , 2004793 . https://doi.org/10.1002/advs.202004793

Title: DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy
Author: Chen, Zhijie; Zhang, Feng; Zhang, Hongbo; Cheng, Liang; Chen, Kaizhe; Shen, Jieliang; Qi, Jin; Deng, Lianfu; He, Chuan; Santos, Helder A.; Cui, Wenguo
Other contributor: University of Helsinki, Nanomedicines and Biomedical Engineering
University of Helsinki, Helsinki One Health (HOH)





Date: 2021-05-05
Language: eng
Number of pages: 17
Belongs to series: Advanced Science
ISSN: 2198-3844
DOI: https://doi.org/10.1002/advs.202004793
URI: http://hdl.handle.net/10138/333017
Abstract: Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1 beta mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA-grafted HA ((DNA)HA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio-stability of the system. After loading SNAs, the constructed (DNA)HA-SNAs system (HA-SNAs) performs a reversible NIR-triggered on-demand release of SNAs by photo-thermal induced DNA dehybridization and followed by post-NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down-regulated catabolic proteases and up-regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.
Subject: anti&#8208
inflammation
DNA grafted hyaluronic acid
enhanced injectability
long&#8208
term bio&#8208
stability
osteoarthritis gene therapy
spherical nucleic acids
116 Chemical sciences
318 Medical biotechnology
221 Nano-technology
317 Pharmacy
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