A5071836454- Muscle Physiology and Disorders
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiomyopathy and Myosin Studies
- Adipose Tissue and Metabolism
- Tissue Engineering and Regenerative Medicine
- CAR-T cell therapy research
- Exercise and Physiological Responses
- Muscle metabolism and nutrition
- Muscle activation and electromyography studies
- Advanced Sensor and Energy Harvesting Materials
- Mitochondrial Function and Pathology
- Herpesvirus Infections and Treatments
- Complex Network Analysis Techniques
- Neurogenetic and Muscular Disorders Research
- Viral gastroenteritis research and epidemiology
- Neonatal Respiratory Health Research
- Retinal Development and Disorders
- Genetic Neurodegenerative Diseases
- Topic Modeling
- Metabolism, Diabetes, and Cancer
- Cardiovascular Effects of Exercise
University of Missouri
2016-2025
Missouri College
2016-2025
First Affiliated Hospital of Xinjiang Medical University
2025
Xinjiang Medical University
2025
Anhui University of Technology
2024
Shenyang University of Technology
2022-2024
Ann Arbor Center for Independent Living
2023
National Computer Network Emergency Response Technical Team/Coordination Center of Chinar
2014-2023
University of Missouri Hospital
2006-2022
Shenyang Center for Disease Control and Prevention
2022
Editing can help build stronger muscles Much of the controversy surrounding gene-editing technology called CRISPR/Cas9 centers on ethics germline editing human embryos to correct disease-causing mutations. For certain disorders such as muscular dystrophy, it may be possible achieve therapeutic benefit by faulty gene in somatic cells. In proof-of-concept studies, Long et al. , Nelson and Tabebordbar used adeno-associated virus-9 deliver system young mice with a mutation coding for dystrophin,...
ABSTRACT Adeno-associated viral (AAV) vectors have demonstrated great utility for long-term gene expression in muscle tissue. However, the mechanisms by which recombinant AAV (rAAV) genomes persist tissue remain unclear. Using a shuttle vector, we that circularized rAAV intermediates impart episomal persistence to The majority of circular had consistent head-to-tail configuration consisting monomer slowly converted large multimers >12 kbp 80 days postinfection. Importantly, transgene was...
Sarcolemma-associated neuronal NOS (nNOS) plays a critical role in normal muscle physiology. In Duchenne muscular dystrophy (DMD), the loss of sarcolemmal nNOS leads to functional ischemia and damage; however, mechanism subcellular localization remains incompletely understood. According prevailing model, is recruited sarcolemma by syntrophin, DMD this altered. Intriguingly, presence syntrophin on membrane does not always restore nNOS. Thus, we wished determine whether dystrophin functions...
Adeno-associated virus (AAV)-mediated CRISPR-Cas9 editing holds promise to treat many diseases. The immune response bacterial-derived Cas9 has been speculated as a hurdle for AAV-CRISPR therapy. However, immunological consequences of AAV-mediated expression have thus far not thoroughly investigated in large mammals. We evaluate Cas9-specific responses canine models Duchenne muscular dystrophy (DMD) following intramuscular and intravenous Treatment results initially robust dystrophin...
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, membrane-stabilizing protein encoded DMD gene. Although mouse models provide insight into potential corrective therapy, data from genetically homologous large animals, such as dystrophin-deficient golden retriever (GRMD) model, may more readily translate to humans. To evaluate clinical translatability an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5)...
The restriction of viral receptors and coreceptors to the basolateral surface airway epithelial cells has been blamed for inefficient transfer vectors apical this tissue. We now report, however, that differentiated human epithelia internalize rAAV type-2 virus efficiently from their surfaces, despite absence known adeno-associated virus–2 (AAV-2) or at these sites. dramatically lower transduction efficiency infection appears result instead differences in endosomal processing nuclear...
Adeno-associated viral (AAV) vectors have demonstrated considerable promise for gene therapy of inherited diseases. However, with a packaging size <5 kb, applications been limited to relatively small disease genes. Based on the finding that AAV genomes undergo intermolecular circular concatamerization after transduction in muscle, we developed paradigm increase delivered transgenes this vector through trans-splicing between two independent coadministered same tissue. When encoding either...
Recombinant adeno-associated (rAAV) viral vectors hold great therapeutic potential for human diseases. However, a relatively small packaging capacity (less than 5 kb) has limited the application of rAAV certain diseases such as cystic fibrosis and Duchenne muscular dystrophy. Here we compared two mechanistically distinct approaches to overcome restraints with vectors. The trans-splicing approach reconstitutes gene expression from independent vectors, each encoding unique, nonoverlapping...
Duchenne muscular dystrophy (DMD) is the most common inherited lethal muscle degenerative disease. Currently there no cure. Highly abbreviated microdystrophin cDNAs were developed recently for adeno-associated virus (AAV)-mediated DMD gene therapy. Among these, a C-terminal-truncated DeltaR4-R23/DeltaC microgene (DeltaR4/DeltaC) has been considered as very promising therapeutic candidate gene. In this study, we packaged CMV.DeltaR4/DeltaC cassette in AAV-5 and evaluated transduction...
Limited packaging capacity hinders adeno-associated virus (AAV) gene therapy. A recent study seems to have provided a solution this problem. Allocca et al. reported that AAV-5 could package an 8.9 kb vector genome. Here we tested whether approach can be used deliver large genome for Duchenne muscular dystrophy (DMD) We first evaluated of 8.2 This carries two independent reporter cassettes, one alkaline phosphatase (AP) and another LacZ. Viral yield was log-fold lower than regular AAV-5....
The success of many gene therapy applications hinges on efficient whole body transduction. In the case muscular dystrophies, a therapeutic vector has to reach every muscle in body. Recent studies suggest that vectors based adeno-associated virus (AAV) are capable body-wide transduction rodents. However, translating this finding large animals remains challenge. Here we explored systemic delivery with AAV serotype-9 (AAV-9) neonatal dogs. Previous attempts directly deliver adult canine have...
The trans-splicing (ts) and overlapping (ov) vectors expand the packaging capacity of adeno-associated virus (AAV). But their application depends on inherent properties target gene. ts require an optimal gene-splitting site ov a highly recombinogenic domain. In order to overcome these limitations, we developed hybrid dual (hd) vector system. hd vectors, inserted alkaline phosphatase (AP) sequence in allow for transgene-independent reconstitution through homologous recombination AP sequences....
Dystrophin deficiency results in lethal Duchenne muscular dystrophy (DMD). Substituting missing dystrophin with abbreviated microdystrophin has dramatically alleviated disease mouse DMD models. Unfortunately, translation of therapy been unsuccessful dystrophic dogs, the only large mammalian model. Approximately 70% dystrophin-coding sequence is removed microdystrophin. Intriguingly, loss ≥50% frequently severe patients. To test whether small gene size constitutes a fundamental design error...
The ultimate goal of muscular dystrophy gene therapy is to treat all muscles in the body. Global delivery was demonstrated dystrophic mice more than a decade ago using adeno-associated virus (AAV). However, translation affected large mammals has been challenging. only reported attempt performed newborn Duchenne (DMD) dogs. Unfortunately, AAV injection resulted growth delay, muscle atrophy and contracture. Here we report safe bodywide juvenile DMD Three ∼2-m-old dogs received intravenous...
Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment old with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. normalized increase proton leak reduced ROS cardiomyocytes from mice, accompanied by protein oxidation shift towards more thiol redox state hearts. Improved diastolic function was concordant increased phosphorylation cMyBP-C Ser282 but independent titin isoform shift....
Abstract Sarcolipin (SLN) is an inhibitor of the sarco/endoplasmic reticulum (SR) Ca 2+ ATPase (SERCA) and abnormally elevated in muscle Duchenne muscular dystrophy (DMD) patients animal models. Here we show that reducing SLN levels ameliorates dystrophic pathology severe dystrophin/utrophin double mutant ( mdx:utr −/− ) mouse model DMD. Germline inactivation one allele gene normalizes expression, restores SERCA function, mitigates skeletal cardiac pathology, improves regeneration, extends...