A5023653908- Virus-based gene therapy research
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Biochemical and Molecular Research
- Bone Tissue Engineering Materials
- Genomics and Rare Diseases
- Biomedical Research and Pathophysiology
- CAR-T cell therapy research
- Viral gastroenteritis research and epidemiology
- Autophagy in Disease and Therapy
- Porphyrin Metabolism and Disorders
- Genetic Neurodegenerative Diseases
- Graphene research and applications
- Sirtuins and Resveratrol in Medicine
- Kidney Stones and Urolithiasis Treatments
- Graphene and Nanomaterials Applications
American Society of Gene Therapy and Cell Therapy
2024
Novo Nordisk (Denmark)
2023
Aarhus University
2023
National Human Genome Research Institute
2015-2022
Stony Brook University
2015-2017
National Institutes of Health
2015-2016
Isolated methylmalonic acidemia/aciduria (MMA) is a devastating metabolic disorder with poor outcomes despite current medical treatments. Like other mitochondrial enzymopathies, enzyme replacement therapy (ERT) not available, and although promising, AAV gene can be limited by pre-existing immunity has been associated genotoxicity in mice. To develop new class of for MMA, we generated pseudoU-modified codon-optimized mRNA encoding human methylmalonyl-CoA mutase (hMUT), the most frequently...
Organic acidemias such as methylmalonic acidemia (MMA) are a group of inborn errors metabolism that typically arise from defects in the catabolism amino and fatty acids. Accretion acyl-CoA species is postulated to underlie disease pathophysiology, but mechanism(s) remain unknown. Here, we surveyed hepatic explants patients with MMA unaffected donors, parallel samples various mouse models methylmalonyl-CoA mutase deficiency. We found widespread posttranslational modification,...
Adeno-associated viral (AAV) gene therapy has shown great promise as an alternative treatment for metabolic disorders managed using liver transplantation, but remains limited by transgene loss and genotoxicity. Our study aims to test AAV vector with a promoterless integrating cassette, designed provide sustained hepatic expression reduced toxicity in comparison canonical therapy.
The assembly of carbon nanomaterials into three-dimensional (3D) porous scaffolds is critical to harness their unique physiochemical properties for tissue engineering and regenerative medicine applications. In this study, we report the fabrication, characterization, in vitro cytocompatibility true 3D (>1 mm all three dimensions), macroscopic (3-8 height 4-6 diameter), chemically cross-linked graphene prepared via radical initiated thermal cross-linking single- multiwalled oxide nanoribbons...
Methylmalonic acidemia (MMA) is a metabolic disorder most commonly caused by mutations in the methylmalonyl-CoA mutase (MMUT) gene. Although adeno-associated viral (AAV) gene therapy has been effective at correcting disease phenotype MMA mouse models, clinical translation may be impaired loss of episomal transgene expression and magnified need to treat patients early life. To achieve permanent correction, we developed dual AAV strategy express codon-optimized MMUT from Alb tested various...
CRISPR-Cas-mediated site-specific integration of transgenes by homology-directed repair (HDR) is challenging, especially in primary cells, where inferior editing efficiency may impede the development gene- and cellular therapies. Various strategies for enrichment cells with transgene integrations have been developed, but most either generate unwanted genomic scars or rely on permanent expression a reporter gene used selection. However, stable perturb cell homeostasis function. Here we...
Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder, in which the body unable to oxidize valine and isoleucine as well odd chain fatty acids. Approximately 60 percent of MMA cases are caused by mutations methylmalonyl-CoA mutase (MUT), enzyme that catalyzes isomerization succinyl-CoA. Current treatments for MUT class include dietary protein restriction cofactor supplementation; however patients continue exhibit severe morbidity high rates mortality. A murine model was...
Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder most frequently resulting from mutations in the mitochondrial localized enzyme, methylmalonyl-CoA mutase (MUT). A mouse model replicating severe form of MMA which there complete loss Mut expression (Mut-/-) displays neonatal lethality but has been successfully used to demonstrate proof-of-principle for gene therapy using AAV vectors. To hepato-, renal and cerebral manifestations MMA, we have generated several lines...