A Rationally Designed Semiconducting Polymer Brush for NIR-II Imaging-Guided Light-Triggered Remote Control of CRISPR/Cas9 Genome Editing
A Rationally Designed Semiconducting Polymer Brush for NIR-II Imaging-Guided Light-Triggered Remote Control of CRISPR/Cas9 Genome Editing
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合理设计的半导体聚合物刷，用于 NIR-II 成像引导光触发远程控制 CRISPR/Cas9 基因组编辑
DOI：
10.1002/adma.201901187
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发表时间：
2019-05-01
影响因子：
29.4
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Li, Ling;Yang, Zhen;Chen, Xiaoyuan
聚类规则间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9 （Cas9）基因组编辑系统在生物医学领域显示出巨大的应用潜力。尽管物理方法、病毒和一些非病毒载体已被用于CRISPR/Cas9传递，并诱导出一些有希望的基因组编辑效果，但精确的基因组编辑仍然具有挑战性，尚未报道。本文报道了基于合理设计的半导体聚合物刷（SPPF）的第二种近红外窗口（NIR-II）成像引导nir光触发CRISPR/Cas9基因组编辑策略的远程控制。SPPF不仅可以作为CRISPR/Cas9载体的载体，还可以在激光照射下通过光热转化控制内溶酶体的逃逸和有效载荷的释放。在激光照射下，SPPF和CRISPR/Cas9卡带的纳米复合物在体外和体内诱导有效的位点特异性精确基因组编辑，毒性最小。此外，基于SPPF的NIR-II成像还可用于监测基因组编辑系统的体内分布，实时引导激光照射。因此，本研究为NIR-II成像引导的nir光触发的CRISPR/Cas9系统的精确基因组编辑提供了一个典型范例。这一策略可能在不久的将来为基于CRISPR/Cas9基因组编辑的精确基因治疗开辟一条道路。
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome-editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near-infrared window (NIR-II) imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 genome-editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site-specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR-II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome-editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR-II imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome-editing-based precise gene therapy in the near future.