A5010920802- Muscle Physiology and Disorders
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Extracellular vesicles in disease
- Tissue Engineering and Regenerative Medicine
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- RNA regulation and disease
- Biomedical Ethics and Regulation
- Epigenetics and DNA Methylation
- Genetic Neurodegenerative Diseases
- Viral Infections and Immunology Research
- Cancer, Hypoxia, and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- Silk-based biomaterials and applications
Nationwide Children's Hospital
2019-2024
The Ohio State University
2016-2023
The Ohio State University Wexner Medical Center
2020-2021
Neurological Surgery
2016
Therapeutic exon skipping as a treatment for Duchenne muscular dystrophy (DMD) has largely concentrated on the delivery of antisense oligomers to treat out-of-frame deletions. Here we report preclinical development an adeno-associated virus (AAV)-encapsidated viral vector containing four copies noncoding U7 small nuclear RNA (U7snRNA), each targeted either splice donor or acceptor sites DMD 2. We have previously shown that this (scAAV9.U7.ACCA) Dup2 mouse model results in expression...
Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping these patients has the potential to be highly therapeutic through restoration full-length dystrophin expression. We conducted 48-week open label study casimersen and golodirsen 3 subjects with an 45 or 53 duplication. Two (aged 18 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, cardiac function appeared stable 2 whom they could evaluated. Dystrophin expression...
In a phase 1/2, open-label dose escalation trial, we delivered rAAVrh74.MCK.GALGT2 (also B4GALNT2) bilaterally to the legs of two boys with Duchenne muscular dystrophy using intravascular limb infusion. Subject 1 (age 8.9 years at dosing) received 2.5 × 1013 vector genome (vg)/kg per leg (5 vg/kg total) and subject 2 6.9 5 (1 1014 total). No serious adverse events were observed. Muscle biopsy evaluated 3 or 4 months post treatment versus baseline showed evidence GALGT2 gene expression...
Duchenne muscular dystrophy is an X-linked disorder typically caused by out-of-frame mutations in the
Exon skipping therapies for Duchenne muscular dystrophy that restore an open reading frame can be induced by the use of noncoding U7 small nuclear RNA (U7snRNA) modified antisense exon-targeting sequence delivered adeno-associated virus (AAV) vector. We have developed AAV vector (AAV9.U7-ACCA) containing four U7snRNAs targeting splice donor and acceptor sites dystrophin exon 2, resulting in highly efficient exclusion DMD 2. assessed specificity variation AAV9.U7-ACCA delivery Dmd 2...
Duchenne muscular dystrophy (DMD) is a progressive X-linked disease caused by mutations in the DMD gene that prevent expression of functional dystrophin protein. Exon duplications represent 6%-11% mutations, and exon 2 (Dup2) are most common (∼11%) duplication mutations. An exon-skipping strategy for Dup2 presents large therapeutic window. Skipping one copy results full-length expression, whereas skipping both copies (Del2) activates an internal ribosomal entry site (IRES) 5, inducing highly...
Abstract Aims Dystrophin, the protein product of DMD gene, plays a critical role in muscle integrity by stabilising sarcolemma during contraction and relaxation. The gene is vulnerable to variety mutations that may cause complete loss, depletion or truncation protein, leading Duchenne Becker muscular dystrophies. Precise reproducible dystrophin quantification essential characterising evaluating outcome efforts induce through therapies. Immunofluorescence microscopy offers high sensitivity...
Duchenne muscular dystrophy (DMD) is a devastating muscle-wasting disease that arises due to the loss of dystrophin expression, leading progressive motor and cardiorespiratory function. Four exon-skipping approaches using antisense phosphorodiamidate morpholino oligomers (PMOs) have been approved by FDA restore DMD open reading frame, resulting in expression functional but internally deleted protein, patients with single-exon duplications, exon skipping has potential full-length expression....
Investigations into both the pathophysiology and therapeutic targets in muscular dystrophies have been hampered by limited proliferative capacity of human myoblasts. Several mouse models created but they either do not truly represent physiopathology disease or are representative broad spectrum mutations found humans. The immortalization primary myoblasts is an alternative to this limitation; however, it still dependent on muscle biopsies, which invasive easily available. In contrast, skin...
Glioblastoma (GBM) represents the most common and aggressive histologic subtype among malignant astrocytoma is associated with poor outcomes because of heterogeneous tumor cell population including mature non-stem like immature stem-like cells within tumor. Thus, it critical to find new target-specific therapeutic modalities. Protein arginine methyltransferase enzyme 5 (PRMT5) regulates many cellular processes through its methylation activity overexpression in GBM more disease. Previously,...