Enhanced Cytosolic Delivery and Release of CRISPR/Cas9 by Black Phosphorus Nanosheets for Genome Editing

被引：188

作者：

Zhou, Wenhua ^{[1
]}

Cui, Haodong ^{[1
]}

Ying, Liming ^{[2
]}

Yu, Xue-Feng ^{[1
]}

机构：

[1] Chinese Acad Sci, Shenzhen Inst Adv Technol, Ctr Biomed Mat & Interfaces, Shenzhen 518055, Peoples R China

[2] Imperial Coll London, Natl Heart & Lung Inst, Mol Med, London SW7 2AZ, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 32期

基金：

中国国家自然科学基金;

关键词：

black phosphorus; CRISPR/Cas9; gene silencing; genome editing; two-dimensional materials; CRISPR-CAS9; NUCLEASES; GRAPHENE; THERAPY; CELLS; NANOMATERIALS; SPECIFICITY; SYSTEM;

D O I：

10.1002/anie.201806941

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：10268 / 10272

页数：5

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