A5010600720- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Hemophilia Treatment and Research
- Diabetes and associated disorders
- Lysosomal Storage Disorders Research
- Diabetes Management and Research
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- Animal Genetics and Reproduction
- SARS-CoV-2 and COVID-19 Research
- Trypanosoma species research and implications
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Child Nutrition and Feeding Issues
- Genetics and Neurodevelopmental Disorders
- Biomedical and Engineering Education
- Glycogen Storage Diseases and Myoclonus
- Herpesvirus Infections and Treatments
- Biosimilars and Bioanalytical Methods
- Research on Leishmaniasis Studies
- Biochemical and Molecular Research
Atara Biotherapeutics (United States)
2024
Spark Therapeutics (United States)
2015-2021
University of Pennsylvania
2017
Children's Hospital of Philadelphia
2010-2015
Howard Hughes Medical Institute
2013-2015
Universitat Autònoma de Barcelona
2006-2012
Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
2009-2012
Gene Therapy Laboratory
2011
The prevention of bleeding with adequately sustained levels clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in treatment hemophilia.
Capsid decoys enhance the efficacy of AAV vector transduction after systemic delivery in presence neutralizing antibodies.
The goal of gene therapy for patients with hemophilia A is to safely impart long-term stable factor VIII expression that predictably ameliorates bleeding the use lowest possible vector dose.In this phase 1-2 trial, we infused an investigational adeno-associated viral (AAV) (SPK-8011) hepatocyte in 18 men A. Four dose cohorts were enrolled; lowest-dose cohort received a 5 × 1011 genomes (vg) per kilogram body weight, and highest-dose 2 1012 vg kilogram. Some participants glucocorticoids...
Adeno-associated virus (AAV) vectors are a leading platform for gene-based therapies both monogenic and complex acquired disorders. The success of AAV gene transfer highlights the need to answer outstanding clinical questions safety, durability, nature human immune response vectors. Here, we present longitudinal follow-up data subjects who participated in first trial systemically delivered vector. Adult males (n = 7) with severe hemophilia B received an AAV2 vector at doses ranging from 8 ×...
Mucopolysaccharidosis type IIIA (MPSIIIA) is an inherited lysosomal storage disease caused by deficiency of sulfamidase, resulting in accumulation the glycosaminoglycan (GAG) heparan sulfate. It characterized severe progressive neurodegeneration, together with somatic alterations, which lead to death during adolescence. Here, we tested ability adeno-associated virus (AAV) vector-mediated genetic modification either skeletal muscle or liver revert already established phenotype 2-month-old...
Abstract Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD currently treated with replacement therapy (ERT) intravenous infusions recombinant human GAA (rhGAA). Although introduction ERT represents breakthrough in management PD, approach suffers from several shortcomings. Here, we developed mouse model to compare efficacy hepatic gene transfer adeno-associated virus (AAV) vectors expressing secretable long-term...
Type 1 diabetic patients develop severe secondary complications because insulin treatment does not guarantee normoglycemia. Thus, efficient regulation of glucose homeostasis is a major challenge in diabetes therapy. Skeletal muscle the most important tissue for disposal after meal. However, lack during impairs uptake. To increase removal from blood, skeletal transgenic mice was engineered both to produce basal levels and express liver enzyme glucokinase. After streptozotozin (STZ)...
In type 1 diabetes, loss of tolerance to β-cell antigens results in T-cell-dependent autoimmune destruction β cells. The abrogation autoreactive T-cell responses is a prerequisite achieve long-lasting correction the disease. liver has unique immunomodulatory properties and hepatic gene transfer induction suppression diseases, part by regulatory (Treg) activation. Hence, could be manipulated treat or prevent diabetes onset through expression key genes. IGF-I may an candidate because it...
Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human have shown translational promise for liver-directed gene therapies. However, many variables that influence hepatocyte transduction and transgene expression such remain poorly defined. Here, we aimed test whether three experimental conditions AAV immunodeficient, fumaryl-acetoactetate-hydrolase-deficient (Fah−/−) chimeric mice repopulated...
We developed a strategy to treat hepatitis C virus (HCV) infection by replacing five endogenous microRNA (miRNA) sequences of natural miRNA cluster (miR-17–92) with that are complementary the HCV genome. This (HCV-miR-Cluster 5) is delivered cells using adeno-associated (AAV) vectors and miRNAs expressed in liver, site replication assembly. AAV-HCV-miR-Cluster 5 inhibited bona fide vitro up 95% within 2 days, spread uninfected was prevented continuous expression anti-HCV miRNAs. Furthermore,...
Extensive clinical data from liver-mediated gene therapy trials have shown that dose-dependent immune responses against the vector capsid may impair or even preclude transgene expression if not managed successfully with prompt suppression. The goal of this preclinical study was to generate an adeno-associated viral (AAV) capable expressing therapeutic levels B-domain deleted factor VIII (FVIII) at lowest possible dose minimize potential Risk a capsid-mediated response in setting. Here, we...