A5048527653- Muscle Physiology and Disorders
- Virus-based gene therapy research
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- Inflammatory Myopathies and Dermatomyositis
- Tissue Engineering and Regenerative Medicine
- Lysosomal Storage Disorders Research
- Muscle metabolism and nutrition
- Calcium signaling and nucleotide metabolism
- Viral Infections and Immunology Research
Nationwide Children's Hospital
2019-2024
rAAVrh74.MCK.GALGT2 is a surrogate gene therapy that inhibits muscular dystrophy in multiple animal models. Here, we report on dose-response study of functional muscle GALGT2 expression as well toxicity and biodistribution studies after systemic intravenous (i.v.) delivery rAAVrh74.MCK.GALGT2. A dose 4.3 × 1014vg/kg (measured with linear DNA standard) resulted GALGT2-induced glycosylation the majority skeletal myofibers throughout body almost all cardiomyocytes, while several lower doses...
GNE myopathy (GNEM) is a severe muscle disease caused by mutations in the UDP-GlcNAc-2-epimerase/ManNAc-6-kinase (GNE) gene, which encodes bifunctional enzyme required for sialic acid (Sia) biosynthesis.To develop assays to demonstrate potency of AAV gene therapy vectors making Sia and define dose replacement endogenous mouse Gne expression with human skeletal muscles.A MyoD-inducible Gne-deficient cell line, Lec3MyoDI, GNE-deficient were made tested various increase binding Sia-specific...
We have examined the effects of intravenous (IV) delivery rAAVrh74.MHCK7. GALGT2 in golden retriever muscular dystrophy (GRMD) model Duchenne Muscular Dystrophy (DMD). After baseline testing, GRMD dogs were treated at 3 months age and reassessed 6 months. This 3–6 month range is a period rapid disease progression, thus offering relatively short window to establish treatment efficacy. Measures analyzed included muscle AAV transduction, transgene expression, -induced glycosylation, pathology,...
Lysosomal acid lipase deficiency (LAL-D) presents as one of two rare autosomal recessive diseases: Wolman disease (WD), a severe disorder presenting in infancy characterized by absent or very low LAL activity, and cholesteryl ester storage (CESD), less severe, later onset form. Recent clinical studies have shown efficacy enzyme replacement therapy for both forms LAL-D; however, no gene approach has yet been developed use. Here, we show that rscAAVrh74.miniCMV.LIPA can significantly improve...