Scott Q. Harper
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View article: Sustained efficacy of CRISPR-Cas13b gene therapy for FSHD is challenged by immune response to Cas13b
Sustained efficacy of CRISPR-Cas13b gene therapy for FSHD is challenged by immune response to Cas13b Open
Facioscapulohumeral muscular dystrophy (FSHD) is a potentially devastating muscle disease caused by de-repression of the toxic DUX4 gene in skeletal muscle. FSHD patients may benefit from DUX4 inhibition therapies, and although several exp…
View article: Identification of disease-specific extracellular vesicle-associated plasma protein biomarkers for Duchenne Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy
Identification of disease-specific extracellular vesicle-associated plasma protein biomarkers for Duchenne Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy Open
Objective Reliable, circulating biomarkers for Duchenne, Becker and facioscapulohumeral muscular dystrophies (DBMD and FSHD) remain unvalidated. Here, we investigated the plasma extracellular vesicle (EV) proteome to identify disease-speci…
View article: Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy
Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy Open
Effective gene therapy for gain-of-function or dominant-negative disease mutations may require eliminating expression of the mutant copy together with wild-type replacement. We evaluated such a knockdown-replace strategy in a mouse model o…
View article: Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis
Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis Open
Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attri…
View article: Post‐Translational Modifications of the <scp>DUX4</scp> Protein Impact Toxic Function in FSHD Cell Models
Post‐Translational Modifications of the <span>DUX4</span> Protein Impact Toxic Function in FSHD Cell Models Open
Objective Facioscapulohumeral muscular dystrophy (FSHD) is caused by abnormal de‐repression of the myotoxic transcription factor DUX4. Although the transcriptional targets of DUX4 are known, the regulation of DUX4 protein and the molecular…
View article: Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis
Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis Open
The monocytic/macrophage system is essential for skeletal muscle homeostasis, but its dysregulation contributes to the pathogenesis of muscle degenerative disorders. Despite our increasing knowledge of the role of macrophages in degenerati…
View article: Posttranslational modifications of the DUX4 protein impact toxic function
Posttranslational modifications of the DUX4 protein impact toxic function Open
Objective Facioscapulohumeral muscular dystrophy (FSHD) is caused by abnormal de-repression of the transcription factor DUX4, which is toxic to muscle in vitro and in vivo . While the transcriptional targets of DUX4 are known, the regulati…
View article: A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice
A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice Open
Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited demyelinating peripheral neuropathy, is caused by PMP22 gene duplication. Overexpression of WT PMP22 in Schwann cells destabilizes the myelin sheath, leading to demyeli…
View article: Is Upregulation of Sarcolipin Beneficial or Detrimental to Muscle Function?
Is Upregulation of Sarcolipin Beneficial or Detrimental to Muscle Function? Open
Sarcolipin (SLN) is a regulator of sarco/endo plasmic reticulum Ca 2+ -ATPase (SERCA) pump and has been shown to be involved in muscle nonshivering thermogenesis (NST) and energy metabolism. Interestingly, SLN expression is significantly u…
View article: Gene Therapy: Charting a Future Course—Summary of a National Institutes of Health Workshop, April 12, 2013
Gene Therapy: Charting a Future Course—Summary of a National Institutes of Health Workshop, April 12, 2013 Open
Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes o…
View article: Allele-specific RNA interference prevents neuropathy in Charcot-Marie-Tooth disease type 2D mouse models
Allele-specific RNA interference prevents neuropathy in Charcot-Marie-Tooth disease type 2D mouse models Open
Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases - where treatment may require redu…
View article: RNAscope in situ hybridization-based method for detecting <i>DUX4</i> RNA expression in vitro
RNAscope in situ hybridization-based method for detecting <i>DUX4</i> RNA expression in vitro Open
Facioscapulohumeral muscular dystrophy (FSHD) is among the most common forms of muscular dystrophy. FSHD is caused by aberrant expression of the toxic DUX4 gene in muscle. Detecting endogenous DUX4 in patient tissue using conventional meth…
View article: AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD
AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD Open
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant or digenic disorder linked to derepression of the toxic DUX4 gene in muscle. There is currently no pharmacological treatment. The emergence of DUX4 enabled development …
View article: Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD)
Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD) Open
FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent hereditary myopathies and is generally characterized by progressive muscle atrophy affecting the face, scapular fixators; upper arms and distal lower legs. The FSHD…
View article: Mouse Dux is myotoxic and shares partial functional homology with its human paralog DUX4
Mouse Dux is myotoxic and shares partial functional homology with its human paralog DUX4 Open
D4Z4 repeats are present in at least 11 different mammalian species, including humans and mice. Each repeat contains an open reading frame encoding a double homeodomain (DUX) family transcription factor. Aberrant expression of the D4Z4 ORF…
View article: 625. RNAi Therapy for Dominant Limb Girdle Muscular Dystrophy Type 1A
625. RNAi Therapy for Dominant Limb Girdle Muscular Dystrophy Type 1A Open
Limb Girdle Muscular Dystrophy (LGMD) refers to a group of disorders characterized by progressive wasting and weakness of pelvic and shoulder girdle muscles. Patients commonly require wheelchair assistance, and individuals with some forms …
View article: 386. Toxicology for DUX4-Targeted MicroRNAs
386. Toxicology for DUX4-Targeted MicroRNAs Open
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder affecting 1 in 7500. Symptoms typically arise in young adulthood and most patients show clinical features before age 30. FSHD is characterized by progressive w…
View article: Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation
Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation Open
Hundreds of double homeobox (DUX) genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscu…