Efficient in vivo gene editing using ribonucleoproteins in skin stem   cells of recessive dystrophic epidermolysis bullosa mouse model

doi:10.1073/pnas.1614775114

CORC > 北京大学 > 生命科学学院

	Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model
	Wu, Wenbo ; Lu, Zhiwei ; Li, Fei ; Wang, Wenjie ; Qian, Nannan ; Duan, Jinzhi ; Zhang, Yu ; Wang, Fengchao ; Chen, Ting
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2017
关键词	in vivo gene editing Cas9/sgRNA ribonucleoproteins skin stem cell electroporation RDEB BASEMENT-MEMBRANE ZONE VII COLLAGEN ANCHORING FIBRILS MUSCULAR-DYSTROPHY INJECTION THERAPY MUSCLE FIBROBLASTS EXPRESSION CORRECTS
DOI	10.1073/pnas.1614775114
英文摘要	The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that non-replicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatalmice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mousemodel, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues.; SCI(E); ARTICLE; 7; 1660-1665; 114
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/475155]
专题	生命科学学院
推荐引用方式 GB/T 7714	Wu, Wenbo,Lu, Zhiwei,Li, Fei,et al. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017.
APA	Wu, Wenbo.,Lu, Zhiwei.,Li, Fei.,Wang, Wenjie.,Qian, Nannan.,...&Chen, Ting.(2017).Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.
MLA	Wu, Wenbo,et al."Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017).