Cas9
清脆的
核糖核蛋白
基因组编辑
化学
DNA
细胞生物学
体内
基因
计算生物学
生物
核糖核酸
生物化学
遗传学
作者
Nachuan Song,Yi Chu,Shuai Li,Yuhang Dong,Xiaoting Fan,Jianpu Tang,Yanfei Guo,Guangshuai Teng,Chi Yao,Dayong Yang
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-09-01
卷期号:9 (35)
被引量:5
标识
DOI:10.1126/sciadv.adi3602
摘要
CRISPR-Cas9 has been explored as a therapeutic agent for down-regulating target genes; the controlled delivery of Cas9 ribonucleoprotein (RNP) is essential for therapeutic efficacy and remains a challenge. Here, we report cascade dynamic assembly/disassembly of DNA nanoframework (NF) that enables the controlled delivery of Cas9 RNP. NF was prepared with acrylamide-modified DNA that initiated cascade hybridization chain reaction (HCR). Through an HCR, single-guide RNA was incorporated to NF; simultaneously, the internal space of NF was expanded, facilitating the loading of Cas9 protein. NF was designed with hydrophilic acylamino and hydrophobic isopropyl, allowing dynamic swelling and aggregation. The responsive release of Cas9 RNP was realized by introducing disulfide bond-containing N,N-bis(acryloyl)cystamine that was specifically in response to glutathione of cancer cells, triggering the complete disassembly of NF. In vitro and in vivo investigations demonstrated the high gene editing efficiency in cancer cells, the hypotoxicity in normal cells, and notable antitumor efficacy in a breast cancer mouse model.
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