Kim, Seongchan Jeong, You Kyeong Cho, Chang Sik Lee, SeokHoon Sohn, Chang Ho Kim, Jeong Hun Jeong, Youngdo Jo, Dong Hyun Bae, Sangsu Lee, Hyojin 2024-01-19T10:04:59Z 2024-01-19T10:04:59Z 2022-12-01 2023-02 2192-2640 https://pubs.kist.re.kr/handle/201004/114070 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. English Wiley-Blackwell Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct Article 10.1002/adhm.202201825 1 Advanced Healthcare Materials, v.12, no.4 Advanced Healthcare Materials 12 4 N scie scopus 000880711900001 Engineering, Biomedical Nanoscience & Nanotechnology Materials Science, Biomaterials Engineering Science & Technology - Other Topics Materials Science Article; Early Access CAS9 RIBONUCLEOPROTEIN GENOMIC DNA CRISPR/CAS9 TARGET STRATEGIES DESIGN CELLS TOOL gene editing porous nanoparticles ribonucleoproteins delivery targeted tumor therapy base editing