Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy

Journal of Neuromuscular Diseases
Courtney S YoungMelissa J Spencer

Abstract

Duchenne muscular dystrophy is caused by mutations in DMD which disrupt the reading frame. Therapeutic strategies that restore DMD's reading frame, such as exon skipping and CRISPR/Cas9, need to be tested in the context of the human DMD sequence in vivo. We have developed a novel dystrophic mouse model by using CRISPR/Cas9 to delete exon 45 in the human DMD gene in hDMD mice, which places DMD out-of-frame. We have utilized this model to demonstrate that our clinically-relevant CRISPR/Cas9 platform, which targets deletion of human DMD exons 45-55, can be directly applied in vivo to restore dystrophin.

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Citations

Oct 17, 2017·Journal of Personalized Medicine·Quynh Nguyen, Toshifumi Yokota
May 3, 2018·Physiological Reviews·Yu ZhangEric N Olson
Dec 20, 2017·Nature Cell Biology·Michael R HicksApril D Pyle
Dec 14, 2018·Journal of Personalized Medicine·Yusuke EchigoyaToshifumi Yokota
Nov 1, 2018·Annual Review of Medicine·Yi-Li MinEric N Olson
May 8, 2019·Human Gene Therapy Methods·Aojie Cai, Xiangdong Kong
Aug 8, 2019·Physiology·Courtney S YoungMelissa J Spencer
Feb 1, 2020·Expert Opinion on Drug Discovery·Nalinda B WasalaDongsheng Duan
Jul 26, 2019·Current Opinion in Neurology·Megan A Waldrop, Kevin M Flanigan
Mar 28, 2020·Genes·Kenji Rowel Q LimToshifumi Yokota
Apr 4, 2020·The International Journal of Neuroscience·Arash SalmaninejadMajid Mojarrad
Feb 2, 2018·Postgraduate Medical Journal·Vassili Crispi, Antonios Matsakas
Sep 22, 2017·JCI Insight·Viktoriia KyrychenkoEric N Olson
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Feb 22, 2018·PloS One·Marcel VeltropMaaike van Putten
Jun 2, 2020·The Journal of Clinical Investigation·Francesco ChemelloEric N Olson
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Jan 7, 2021·Expert Opinion on Biological Therapy·Tejal AsleshToshifumi Yokota
Apr 7, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Eunyoung Choi, Taeyoung Koo
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Sep 13, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adrian Pickar-OliverCharles A Gersbach

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Methods Mentioned

BETA
antisense oligonucleotides
in vitro transcription
PCR
Genotyping

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