A5021085969- Muscle Physiology and Disorders
- Virus-based gene therapy research
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- RNA modifications and cancer
- Neurofibromatosis and Schwannoma Cases
- Neuroblastoma Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Advanced Sensor and Energy Harvesting Materials
- RNA regulation and disease
- Telomeres, Telomerase, and Senescence
- RNA and protein synthesis mechanisms
- Silk-based biomaterials and applications
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced biosensing and bioanalysis techniques
- Pluripotent Stem Cells Research
- Muscle activation and electromyography studies
- Cardiac Fibrosis and Remodeling
- Cardiomyopathy and Myosin Studies
- Adipose Tissue and Metabolism
- Innovative Microfluidic and Catalytic Techniques Innovation
- Exercise and Physiological Responses
Royal Holloway University of London
2015-2024
Teesside University
2022-2024
Hôpital Necker-Enfants Malades
2012
KU Leuven
2012
Université Paris Cité
2012
Centre National de la Recherche Scientifique
2012
Inserm
2012
Hammersmith Hospital
2009
Imperial College London
2009
Weatherford College
2009
Mutations that disrupt the open reading frame and prevent full translation of DMD, gene encodes dystrophin, underlie fatal X-linked disease Duchenne muscular dystrophy. Oligonucleotides targeted to splicing elements (splice switching oligonucleotides) in DMD pre-mRNA can lead exon skipping, restoration frame, production functional dystrophin vitro vivo, which could benefit patients with this disorder.We did a single-blind, placebo-controlled, dose-escalation study recruited nationally,...
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result absence of functional protein. In majority cases these are out-of-frame deletions disrupt reading frame. Several attempts have been made to restore mRNA frame modulation pre-mRNA splicing with antisense oligonucleotides (AOs), demonstrating success cultured cells, muscle explants, and animal models. We preparing for a phase I/IIa clinical trial aimed at assessing safety effect locally administered AOs...
Recombinant adeno-associated virus (rAAV) vectors have been shown to permit very efficient widespread transgene expression in skeletal muscle after systemic delivery, making these increasingly attractive as for Duchenne muscular dystrophy (DMD) gene therapy. DMD is a severe muscle-wasting disorder caused by mutations leading complete loss of dystrophin protein. One the major issues associated with delivery gene, therapeutic approach DMD, its large open reading frame (ORF; 11.1 kb). A series...
Defects in mRNA 3′end formation have been described to alter transcription termination, transport of the from nucleus cytoplasm, stability and translation efficiency. Therefore, inhibition polyadenylation may lead gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model determine whether or not targeting key 3′ end elements involved processing using antisense oligonucleotide drugs can be used strategy for silencing within potentially therapeutic context. FSHD is...
Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle-wasting disease caused by mutations in the DMD gene. In 51% of cases, reading frame disrupted because deletion several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as gene-editing tool to correct an out-of-frame Dmd exon knockout mice. Herein, Cas9 S. pyogenes generate mice with frameshift mutation Then, expressed CjCas9, its single-guide RNA, and EGFP gene tibialis anterior muscle using...
Duchenne muscular dystrophy (DMD) is caused by out-of-frame mutations of the human DMD gene. Antisense oligonucleotides (AOs) have previously been used to skip additional exons that border deletions such reading frame restored and internally truncated, but functional, dystrophin expressed. We designed phosphorodiamidate morpholino oligomer (PMO) AOs various PMOs were their target sites overlapping areas open RNA structure, as defined hybridization-array analysis, likely exonic splicing...
The ability to specifically engineer the genome of living cells at precise locations using rare-cutting designer endonucleases has broad implications for biotechnology and medicine, particularly functional genomics, transgenics gene therapy. However, potential impact chromosomal context epigenetics on endonuclease-mediated editing is poorly understood. To address this question, we conducted a comprehensive analysis efficacy 37 derived from quintessential I-CreI meganuclease that were...
Duchenne muscular dystrophy (DMD) is a severe inherited, muscle-wasting disorder caused by mutations in the DMD gene. Gene therapy development for has concentrated on vector-based minigene transfer, cell-based gene using genetically modified adult muscle stem cells or healthy wild-type donor cells, and antisense oligonucleotide-induced exon-skipping to restore reading frame of mutated This study an investigation into targeting-mediated correction deletions human patient myoblasts...
Myostatin is a negative regulator of muscle mass, and several strategies are being developed to knockdown its expression improve muscle-wasting conditions. Strategies using antimyostatin-blocking antibodies, inhibitory-binding partners, signal transduction blockers, RNA interference system (RNAi)-based have yielded promising results increased mass in experimental animals. These approaches have, however, number disadvantages such as transient effects or adverse immune complications. We report...
Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for expression skeletal muscles. To overcome limited packaging capacity of AAV (<5 kb), truncated recombinant microdystrophin with deletions most rod and carboxyl-terminal (CT) domains developed. We previously shown efficiency mRNA sequence-optimized (ΔR4-23/ΔCT, called MD1)...
Abstract During the last decade, multiple clinical trials for Duchenne muscular dystrophy (DMD) have focused on induction of dystrophin expression using different strategies. Many these reported a clear increase in protein following treatment. However, low levels induced raised questions its functionality. In our present study, an unbiased, high-throughput digital image analysis platform, we assessed markers regeneration and associated via immunofluorescent whole muscle sections 25 DMD boys...
Periostin, a multifunctional 90 kDa protein, plays pivotal role in the pathogenesis of fibrosis across various tissues, including skeletal muscle. It operates within transforming growth factor beta 1 (Tgf-β1) signalling pathway and is upregulated fibrotic tissue. Alternative splicing Periostin’s C-terminal region leads to six protein-coding isoforms. This study aimed elucidate contribution isoforms containing amino acids encoded by exon 17 (e17+ Periostin) muscle investigate therapeutic...
ABSTRACT Alpha-dystroglycan is a glycoprotein expressed on the surface of skeletal muscle fibres and other cell types. In muscle, α-dystroglycan provides link between myofibre cytoskeleton through its indirect binding to dystrophin, basal lamina laminin-2, protein extracellular matrix. The disruption this linkage matrix common feature Duchenne muscular dystrophies, though pathogenic mechanisms leading wasting remain unknown. By treating primary mouse cultures with monoclonal antibody which...
The knockdown of myostatin, a negative regulator skeletal muscle mass may have important implications in disease conditions accompanied by loss like cancer, HIV/AIDS, sarcopenia, atrophy, and Duchenne muscular dystrophy (DMD). In DMD patients, where major has occurred due to lack dystrophin, the therapeutic restoration dystrophin expression alone older patients not be sufficient restore functionality muscles. We recently demonstrated that phosphorodiamidate morpholino oligomers (PMOs) can...
Abstract Background Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset muscle disease affecting one per 80 000 of the general population characterized by profound dysphagia and ptosis, limb weakness at later stages. Affected muscles are increased fibrosis atrophy. Myostatin negative regulator mass, inhibition myostatin has been demonstrated to ameliorate symptoms in dystrophic muscles. Methods In this study, we performed systemic delivery monoclonal antibody immunologically block A17...
Antisense-mediated exon skipping is a promising approach for the treatment of Duchenne muscular dystrophy (DMD), rare life-threatening genetic disease due to dystrophin deficiency. Such an can restore disrupted reading frame pre-mRNA, generating truncated form protein. Alternatively, antisense therapy be used induce destructive myostatin knocking down expression enhance muscle strength and reduce fibrosis. We have reported previously that intramuscular or intraperitoneal administration...
Abstract Current therapeutic options for treating colorectal cancer have little clinical efficacy and acquired resistance during treatment is common, even following patient stratification. Understanding the mechanisms that promote therapy may lead to development of novel complement existing treatments improve outcome. Here, we identify RAC1B as an important mediator tumourigenesis a potential target enhancing EGFR inhibitor treatment. We find high expression in human associated with...
Duchenne muscular dystrophy (DMD) is a severe, progressive genetic disorder primarily affecting boys, characterized by muscle degeneration due to mutations in the DMD gene encoding dystrophin, crucial protein for fiber integrity. The disease leads significant weakness and eventually loss of ambulation. AAV-microdystrophin therapy shows promise preclinical clinical settings. However, fibrosis, consequence chronic inflammation extracellular matrix (ECM) remodeling, exacerbates progression may...
Duchenne muscular dystrophy (DMD) is a devastating X-linked recessive genetic myopathy. DMD physiopathology still not fully understood and prenatal onset suspected but difficult to address. The bone morphogenetic protein 4 (BMP4) critical signaling molecule involved in mesoderm commitment. Human induced pluripotent stem cells (hiPSCs) from healthy individuals human embryonic (hESCs) treated with BMP4 allowed us model the early steps of myogenesis normal contexts. Unexpectedly, 72h following...
Research Article14 December 2017Open Access Source DataTransparent process Reversible immortalisation enables genetic correction of human muscle progenitors and engineering next-generation artificial chromosomes for Duchenne muscular dystrophy Sara Benedetti Department Cell Developmental Biology, University College London, UK Great Ormond Street Institute Child Health, Search more papers by this author Narumi Uno Biomedical Science, Regenerative Medicine Biofunction, Tottori University,...