Details

Autor(en) / Beteiligte

• Li, Ling
• Song, Linjiang
• Liu, Xiaowei
• Yang, Xi
• Li, Xia
• He, Tao
• Wang, Ning
• Yang, Suleixin
• Yu, Chuan
• Yin, Tao
• Wen, Yanzhu
• He, Zhiyao
• Wei, Xiawei
• Su, Weijun
• Wu, Qinjie
• Yao, Shaohua
• Gong, Changyang
• Wei, Yuquan

Titel

Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice

Ist Teil von

• ACS nano, 2017-01, Vol.11 (1), p.95-111

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• CRISPR-Cas9 has emerged as a versatile genome-editing platform. However, due to the large size of the commonly used CRISPR-Cas9 system, its effective delivery has been a challenge and limits its utility for basic research and therapeutic applications. Herein, a multifunctional nucleus-targeting “core-shell” artificial virus (RRPHC) was constructed for the delivery of CRISPR-Cas9 system. The artificial virus could efficiently load with the CRISPR-Cas9 system, accelerate the endosomal escape, and promote the penetration into the nucleus without additional nuclear-localization signal, thus enabling targeted gene disruption. Notably, the artificial virus is more efficient than SuperFect, Lipofectamine 2000, and Lipofectamine 3000. When loaded with a CRISPR-Cas9 plasmid, it induced higher targeted gene disruption efficacy than that of Lipofectamine 3000. Furthermore, the artificial virus effectively targets the ovarian cancer via dual-receptor-mediated endocytosis and had minimum side effects. When loaded with the Cas9-hMTH1 system targeting MTH1 gene, RRPHC showed effective disruption of MTH1 in vivo. This strategy could be adapted for delivering CRISPR-Cas9 plasmid or other functional nucleic acids in vivo.