A5115444798- Virus-based gene therapy research
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- Hemophilia Treatment and Research
- Lysosomal Storage Disorders Research
- Trypanosoma species research and implications
- Viral Infections and Immunology Research
- Child Nutrition and Feeding Issues
- Biosimilars and Bioanalytical Methods
- Glycogen Storage Diseases and Myoclonus
- Cytomegalovirus and herpesvirus research
- Cystic Fibrosis Research Advances
- Celiac Disease Research and Management
- RNA Interference and Gene Delivery
- Biosensors and Analytical Detection
- Cell Image Analysis Techniques
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Autoimmune and Inflammatory Disorders Research
BioMarin (United States)
2016-2024
University of North Carolina at Chapel Hill
2007
The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place New Orleans, LA, USA April 1–5, with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event – full immersion week bioanalysis, biomarkers, immunogenicity gene therapy. As usual, it specifically designed to facilitate sharing, reviewing, discussing agreeing...
Gene therapy may offer a new treatment option, particularly for patients with severe hemophilia, based on recent research. However, individuals pre-existing immunity to adeno-associated viruses (AAVs) be less likely benefit from AAV vector-based therapies. To study AAV5 in humans, we validated two complementary, sensitive, and scalable vitro assays detect total antibodies transduction inhibition (TI). Using these assays, found that 53% of samples 100 healthy male were negative both 18%...
Adeno-associated virus (AAV)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type AAV is unclear. In addition, other poorly defined plasma factors could inhibit vector transduction where not detected. To better define relationship between various forms immunity and transfer, we studied valoctocogene roxaparvovec (BMN 270) in cynomolgus monkeys with varying pre-dose levels neutralizing anti-AAV non-antibody inhibitors....
Evaluation of immune responses to adeno-associated virus (AAV)-mediated gene therapies prior and following dose administration plays a key role in determining therapeutic safety efficacy. This report describes up 3 years immunogenicity data valoctocogene roxaparvovec (BMN 270), an AAV5-mediated therapy encoding human B domain-deleted FVIII (hFVIII-SQ) phase 1/2 clinical study adult males with severe hemophilia A. Patients pre-existing humoral immunity AAV5 or history inhibitors were excluded...
Recombinant adeno-associated virus (AAV) vectors are the leading delivery vehicle used for
The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held 27 September to 1 October 2021. Even with a last-minute move from in-person virtual, an overwhelmingly high number nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), multiple regulatory agencies still eagerly convened actively discuss most current topics interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned week...
Abstract Adeno-Associated Virus (AAV)-based gene therapy vectors are in development for many inherited human disorders. In nonclinical studies, cellular immune responses mediated by cytotoxic T cells may target vector-transduced cells, which could impact safety and efficacy. Here, we describe the bioanalytical validation of an interferon-gamma (IFN-γ)-based Enzyme-Linked Immunospot (ELISpot) assay measuring cell against viral antigens cynomolgus monkeys. Since ELISpots performed with...
Adeno-associated virus (AAV)-based gene therapies have recently shown promise as a novel treatment for hereditary diseases. Due to the viral origin of vector capsid, however, cellular immune response may be elicited that could eliminate transduced target cells. To monitor responses in clinical trials, we optimized and bioanalytically validated sensitive, robust, reliable interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay. For method performance validation, human peripheral blood...
Adeno-associated virus gene therapy has been the subject of intensive investigation for monogenic disease addition more than 25 years, yet few therapies have approved by regulatory agencies. Most not progressed beyond phase 1/2 due to toxicity, lack efficacy, or both. The liver is a natural target adeno-associated since most serotypes high degree tropism hepatocytes cell surface receptors and unique sinusoidal geometry facilitating volumes blood contact with hepatocyte surfaces. Recessive...
Elosulfase alfa is an enzyme replacement therapy for the treatment of Morquio A syndrome (mucopolysaccharidosis IVA), a lysosomal storage disorder caused by deficiency N-acetylgalactose-amine-6-sulfatase. We previously reported immunogenicity data from our 24-week placebo-controlled Phase III study, MOR-004. Here, we report long-term profile elosulfase MOR-005, extension trial to assess potential correlations between antidrug antibodies and efficacy safety outcomes throughout 120 weeks...
Abstract A major issue regarding T cell responses in autoimmunity is how the repertoire compares between periphery and target organ. In type 1 diabetes, status of at-risk or diabetic individuals can be monitored by measuring β cell-specific cells isolated from PBL, but whether these accurately reflect residing pancreatic islets unclear. The TCR disease-relevant, tetramer-sorted CD8+ was examined at single-cell level lymph nodes (PLN), individual NOD mice. CDR3α CDR3β sequences demonstrated...
Elosulfase alfa is an enzyme replacement therapy for Morquio A syndrome (mucopolysaccharidosis IVA), a multisystemic progressive lysosomal storage disorder. This report includes the primary treatment outcomes and immunogenicity profile of elosulfase in patients with from 2 sequential studies, MOR-002 (ClinicalTrials.govNCT00884949) MOR-100 (NCT01242111), representing >5 years clinical study data. was open-label, single-arm phase 1/2 that evaluated pharmacokinetics, safety, immunogenicity,...
Many enzyme replacement therapies (ERTs) for lysosomal storage disorders use the cell-surface cation-independent mannose-6 phosphate receptor (CI-M6PR) to deliver ERTs lysosome. However, neutralizing antibodies (NAb) may interfere with this process. We previously reported that most individuals Morquio A who received elosulfase alfa in phase 3 MOR-004 trial tested positive NAbs capable of interfering binding CI-M6PR ectodomain an ELISA-based assay. no correlation was detected between NAb...
Replication-incompetent adeno-associated virus (AAV)-based vectors are nonpathogenic viral particles used to deliver therapeutic genes treat multiple monogenic disorders. AAVs can elicit immune responses; thus, one challenge in AAV-based gene therapy is the presence of neutralizing antibodies against vector capsids that may prevent transduction target cells or adverse findings. We present safety findings from two 12-week studies nonhuman primates (NHPs) with pre-existing treatment-emergent...
Introduction Seroprevalence studies indicate many prospective gene therapy (GT) patients have been previously exposed to adeno-associated viruses (AAV) and harbor pre-existing AAV antibodies which may impact the administration efficacy of GT. The objective this study was further characterize antibody responses serotype 5 (AAV5) in severe hemophilia A (n=540) who are GT naïve.
Introduction The investigation of adeno associated virus (AAV) vectored gene therapies has increased exponentially over the past decade for treatment monogenic disorders. However, presence pre-existing anti-AAV neutralizing antibodies (AAV NAb) may limit efficacy therapy. Moreover, a first administration an AAV vector induces high titers emergent NAb, which compromise repeat dose with same vector. Depletion NAb by immunoadsorption plasmapheresis (IAP) is strategy that could allow successful...
Introduction AAV-mediated gene therapy vectors represent a complex drug design with multiple components that may impact immunogenicity. Clinical trials monitor immunogenicity directed toward both the vector delivery system and expressed transgene product. Valoctocogene roxaparvovec is an AAV5-mediated under investigation for treatment of hemophilia A encodes codon-optimized B-domain deleted human FVIII protein (hFVIII-SQ) control liver-selective promoter. This report describes clinical...