Effective Genome Editing Using CRISPR-Cas9 Nanoflowers

被引:9
作者
Zhang, Chen [1 ]
Ren, He [1 ]
Liu, Gengqi [1 ]
Li, Jiexin [1 ]
Wang, Xiaojie [1 ]
Zhang, Yumiao [1 ]
机构
[1] Tianjin Univ, Sch Chem Engn & Technol, Key Lab Syst Bioengn, Minist Educ, Tianjin 300350, Peoples R China
基金
中国国家自然科学基金;
关键词
CRISPR-Cas9; nanoflowers; polymeric micelles; traceless release; anti-tumor therapy; CAS9; RIBONUCLEOPROTEIN; CELLULAR UPTAKE; DELIVERY; NANOPARTICLES; MECHANISMS; STRATEGIES; MICELLES; RELEASE; PROTEIN; SYSTEM;
D O I
10.1002/adhm.202102365
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
CRISPR-Cas9 as a powerful gene-editing tool has tremendous potential for the treatment of genetic diseases. Herein, a new mesoporous nanoflower (NF)-like delivery nanoplatform termed Cas9-NF is reported by crosslinking Cas9 and polymeric micelles that enables efficient intracellular delivery and controlled release of Cas9 in response to reductive microenvironment in tumor cells. The flower morphology is flexibly tunable by the protein concentration and different types of crosslinkers. Cas9 protein, embedded between polymeric micelles and protected by Cas9-NF, remains stable even under extreme pH conditions. Responsive cleavage of crosslinkers in tumor cells, leads to the traceless release of Cas9 for efficient gene knockout in nucleus. This crosslinked nanoparticle exhibits excellent capability of downregulating oncogene expression and inhibiting tumor growth in a murine tumor model. Taken together, these findings pave a new pathway toward the application of the protein-micelle crosslinked nanoflower for protein delivery, which warrants further investigations for gene regulation and cancer treatment.
引用
收藏
页数:12
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