Enhanced Cytosolic Delivery and Release of CRISPR/Cas9 by Black Phosphorus Nanosheets for Genome Editing
Enhanced Cytosolic Delivery and Release of CRISPR/Cas9 by Black Phosphorus Nanosheets for Genome Editing
复制标题
通过黑磷纳米片增强 CRISPR/Cas9 的胞质传递和释放，用于基因组编辑。
DOI：
10.1002/anie.201806941
复制
发表时间：
2018-08-06
影响因子：
16.6
通讯作者：
Yu, Xue-Feng
中科院分区：
文献类型：
--
作者：
Zhou, Wenhua;Cui, Haodong;Yu, Xue-Feng
成功地建立了一种可生物降解的二维（2D）递送平台，该平台基于将在C末端具有三个核定位信号（NLS）的Cas9核糖核蛋白（Cas9 N3）负载于黑磷纳米片（BP）。Cas9 N3-BP通过膜渗透和内吞途径有效地进入细胞，随后是BP生物降解相关的内体逃逸和负载的Cas9 N3复合物的胞质释放。因此，与其他基于纳米颗粒的递送平台相比，Cas9 N3-BP以相对低的剂量在体外和体内提供有效的基因组编辑和基因沉默。这种可生物降解的2D递送平台为CRISPR/Cas9核糖核蛋白和其他生物活性大分子的生物医学应用提供了一种通用的胞质递送方法。
A biodegradable two-dimensional (2D) delivery platform based on loading black phosphorus nanosheets (BPs) with Cas9 ribonucleoprotein engineered with three nuclear localization signals (NLSs) at C terminus (Cas9N3) is successfully established. The Cas9N3-BPs enter cells effectively via membrane penetration and endocytosis pathways, followed by a BPs biodegradation-associated endosomal escape and cytosolic releases of the loaded Cas9N3 complexes. The Cas9N3-BPs thus provide efficient genome editing and gene silencing invitro and invivo at a relatively low dose as compared with other nanoparticle-based delivery platforms. This biodegradable 2D delivery platform offers a versatile cytosolic delivery approach for CRISPR/Cas9 ribonucleoprotein and other bioactive macromolecules for biomedical applications.