한빛사 논문
Seongchan Kim 1, You Kyeong Jeong 2, Chang Sik Cho 3, SeokHoon Lee 4, Chang Ho Sohn 5, Jeong Hun Kim 3 6, Youngdo Jeong 1, Dong Hyun Jo 7, Sangsu Bae 2 4, Hyojin Lee 1 8
1Biomaterials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), 02792, Seoul, Republic of Korea.
2Medical Research Center of Genomic Medicine Institute, Seoul National University College of Medicine, 03080, Seoul, Republic of Korea.
3Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, 03080, Seoul, Republic of Korea.
4Department of Biomedical Sciences, Seoul National University College of Medicine, 03080, Seoul, Republic of Korea.
5Center for Nanomedicine, Institute for Basic Science, Graduate Program in Nanobiomedical Engineering, Advanced Science Institute, Yonsei University, 03722, Seoul, Republic of Korea.
6Department of Ophthalmology and Department of Biomedical Sciences, Seoul National University College of Medicine, 03080, Seoul, Republic of Korea.
7Department of Anatomy and Cell Biology, Seoul National University College of Medicine, 03080, Seoul, Republic of Korea.
8Division of Bio-Medical Science & Technology, KIST School - Korea University of Science and Technology (UST), 02792, Seoul, Republic of Korea.
S.K. and Y.K.J. contributed equally to this work.
CORRESPONDING AUTHORS: Dong Hyun Jo, Sangsu Bae, Hyojin Lee
Abstract
Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.
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