CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice
Yu Zhang,Chengzu Long,Hui Li,John R. McAnally,Kedryn K. Baskin,John M. Shelton,Rhonda Bassel-Duby,Eric N. Olson +7 more
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TLDR
These findings are the first to show the efficiency of Cpf1-mediated correction of genetic mutations in human cells and an animal disease model and represent a significant step toward therapeutic translation of gene editing for correction of DMD.Abstract:
Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin gene (DMD), is characterized by fatal degeneration of striated muscles. Dilated cardiomyopathy is one of the most common lethal features of the disease. We deployed Cpf1, a unique class 2 CRISPR (clustered regularly interspaced short palindromic repeats) effector, to correct DMD mutations in patient-derived induced pluripotent stem cells (iPSCs) and mdx mice, an animal model of DMD. Cpf1-mediated genomic editing of human iPSCs, either by skipping of an out-of-frame DMD exon or by correcting a nonsense mutation, restored dystrophin expression after differentiation to cardiomyocytes and enhanced contractile function. Similarly, pathophysiological hallmarks of muscular dystrophy were corrected in mdx mice following Cpf1-mediated germline editing. These findings are the first to show the efficiency of Cpf1-mediated correction of genetic mutations in human cells and an animal disease model and represent a significant step toward therapeutic translation of gene editing for correction of DMD.read more
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EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs
Yan Wang,Xie Yinping,Lili Li,Yuan He,Di Zheng,Pengcheng Yu,Ling Yu,Lixu Tang,Yibin Wang,Zhihua Wang +9 more
TL;DR: A global screening for EZH2-binding lncRNAs in tissues including brain, lung, heart, liver, kidney, intestine, spleen, testis, muscle and blood by combining RNA immuno-precipitation and RNA sequencing suggests critical roles of lnc RNAs during cell differentiation and maturation.
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Duchenne muscular dystrophy: an updated review of common available therapies
Arash Salmaninejad,Saeed Farajzadeh Valilou,Hadi Bayat,Nader Ebadi,Abdolreza Daraei,Meysam Yousefi,Abolfazl Nesaei,Majid Mojarrad +7 more
TL;DR: This review provides an update on the recent gene therapies for DMD that aim to compensate for dystrophin deficiency and the related clinical trials.
Journal ArticleDOI
Efficient precise in vivo base editing in adult dystrophic mice.
Li Xu,Chen Zhang,Haiwen Li,Peipei Wang,Yandi Gao,Nahush A. Mokadam,Jianjie Ma,W. David Arnold,Renzhi Han +8 more
TL;DR: The promise of permanent base editing using iABE-NGA for the treatment of monogenic diseases is highlighted and the high efficiency to precisely edit a Duchenne muscular dystrophy (DMD) mutation in adult mice is demonstrated.
Journal ArticleDOI
KLHL41 stabilizes skeletal muscle sarcomeres by nonproteolytic ubiquitination
Andres Ramirez-Martinez,Bercin Kutluk Cenik,Svetlana Bezprozvannaya,Beibei Chen,Rhonda Bassel-Duby,Ning Liu,Eric N. Olson +6 more
TL;DR: It is shown that KLHL41 is poly-ubiquitinated and acts, at least in part, by preventing aggregation and degradation of Nebulin, an essential component of the sarcomere, suggesting a unique role for ubiquitination in protein stabilization.
Journal ArticleDOI
Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells.
Miaojin Zhou,Zhiqing Hu,Liyan Qiu,Tao Zhou,Mai Feng,Qian Hu,Baitao Zeng,Zhuo Li,Qianru Sun,Yong Wu,Xionghao Liu,Lingqian Wu,Desheng Liang +12 more
TL;DR: In this article, a unique crRNA was designed that does not have similar sequences (≤3 mismatches) anywhere in the human reference genome, and in situ gene conversion of the SMN2 gene to an SMN1-like gene in SMA-iPSCs was achieved using CRISPR/Cpf1 and single-stranded oligodeoxynucleotide with a high efficiency of 4/36.
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