2021
DOI: 10.1016/j.omtm.2020.12.001
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Targeted epigenetic repression by CRISPR/dSaCas9 suppresses pathogenic DUX4-fl expression in FSHD

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Cited by 40 publications
(35 citation statements)
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“…69 This misexpression ultimately leads to an immune deregulation cascade, 68 and can be repressed by targeted epigenetic editing. 70 Notably, the DUX4 DNA hypomethylation in FSHD directionally corresponds with the DUX4 co-methylation network we observed in hippocampus, where the maternal obesity with no intervention group was hypomethylated when compared to the control and obesity intervention groups.…”
Section: Discussionsupporting
confidence: 59%
“…69 This misexpression ultimately leads to an immune deregulation cascade, 68 and can be repressed by targeted epigenetic editing. 70 Notably, the DUX4 DNA hypomethylation in FSHD directionally corresponds with the DUX4 co-methylation network we observed in hippocampus, where the maternal obesity with no intervention group was hypomethylated when compared to the control and obesity intervention groups.…”
Section: Discussionsupporting
confidence: 59%
“…One obvious advantage over murine transgenic models is that human-to-mouse muscle xenografts are comprised almost exclusively of human tissue and thus provide the best source of mature human muscle, outside of the clinic, to study the specificity and efficacy of drugs designed to treat FSHD. In particular, xenograft models of FSHD are the only setting in which therapeutic approaches targeting the FSHD locus and DUX4 epigenetic or transcriptional regulation [ 157 , 159 , 160 , 161 , 162 , 163 , 164 , 165 ] can be tested in vivo.…”
Section: Animal Models Of Fshdmentioning
confidence: 99%
“…Clinical management involving physiotherapies, vision and hearing aids, orthopedic interventions, pain and fatigue management or surgical scapular fixation has shown some clinical benefit and improved the quality of life for FSHD patients ( 49 , 50 ). Since aberrant expression of the DUX4 gene has been extensively reported as the main causative factor of FSHD ( 9–14 , 20 ), pre-clinical strategies silencing DUX4 expression have shown promise for FSHD treatment ( 20 , 22 , 24 , 29 , 41 , 51–53 ). Among antisense approaches, those targeting the pLAM region of DUX4 3′UTR, including ours, have provided the best down-regulatory effect ( 20 , 24 , 29 , 30 ).…”
Section: Discussionmentioning
confidence: 99%
“…This is because most studies have been conducted in cell cultures. Several groups made further efforts, investigating the therapeutic benefit in FSHD animal models ( 29 , 30 , 41 , 52 ), but all studies so far have employed a local intramuscular administration. Optimizing a systemic therapy is clinically important because any treatment for FSHD will need to suppress DUX4 expression in a large number of skeletal muscles.…”
Section: Discussionmentioning
confidence: 99%
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