A Photolabile Semiconducting Polymer Nanotransducer for Near-Infrared Regulation of CRISPR/Cas9 Gene Editing
A Photolabile Semiconducting Polymer Nanotransducer for Near-Infrared Regulation of CRISPR/Cas9 Gene Editing
复制标题
用于CRISPR/Cas9基因编辑近红外调控的光敏半导体聚合物纳米换能器
DOI：
10.1002/anie.201909264
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发表时间：
2019-10-30
影响因子：
16.6
通讯作者：
Pu, Kanyi
中科院分区：
文献类型：
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作者：
Lyu, Yan;He, Shasha;Pu, Kanyi
CRISPR/Cas9基因编辑的非侵入性调控有助于理解基因功能和开发基因治疗;然而，它仍然具有挑战性。在本文中，合成了一种光不稳定的半导体聚合物纳米转换器（pSPN），作为基因载体将CRISPR/Cas9质粒递送到细胞中，也作为光调节剂远程激活基因编辑。pSPN包含通过O-1（2）-可裂解的连接基用聚乙烯亚胺刷接枝的O-1（2）-生成主链。NIR光照射自发地触发基因载体从pSPN的切割，导致CRISPR/Cas9质粒的释放，随后启动基因编辑。该系统提供了15和1.8倍的增强修复的基因表达相对于未照射的控制在活细胞和小鼠，分别。由于这种方法不需要对生物分子组分进行任何特定的修饰，pSPN代表了第一个用于体内调控CRISPR/Cas9基因编辑的通用纳米转换器。
Noninvasive regulation of CRISPR/Cas9 gene editing is conducive to understanding of gene function and development of gene therapy; however, it remains challenging. Herein, a photolabile semiconducting polymer nanotransducer (pSPN) is synthesized to act as the gene vector to deliver CRISPR/Cas9 plasmids into cells and also as the photoregulator to remotely activate gene editing. pSPN comprises a O-1(2)-generating backbone grafted with polyethylenimine brushes through O-1(2)-cleavable linkers. NIR photoirradiation spontaneously triggers the cleavage of gene vectors from pSPN, resulting in the release of CRISPR/Cas9 plasmids and subsequently initiating gene editing. This system affords 15- and 1.8-fold enhancement in repaired gene expression relative to the nonirradiated controls in living cells and mice, respectively. As this approach does not require any specific modifications on biomolecular components, pSPN represents the first generic nanotransducer for in vivo regulation of CRISPR/Cas9 gene editing.