A5075244777- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Retinal Development and Disorders
- Viral gastroenteritis research and epidemiology
- Blood groups and transfusion
- Retinal Diseases and Treatments
- Fungal and yeast genetics research
- Platelet Disorders and Treatments
- Biofuel production and bioconversion
- Retinal and Macular Surgery
- Immune Cell Function and Interaction
- Ocular Disorders and Treatments
- S100 Proteins and Annexins
- Retinal and Optic Conditions
- Mesenchymal stem cell research
- T-cell and B-cell Immunology
- Hemophilia Treatment and Research
- Microbial Metabolic Engineering and Bioproduction
- Hemoglobinopathies and Related Disorders
- Toxin Mechanisms and Immunotoxins
- Complement system in diseases
Oxford BioMedica (United Kingdom)
2017-2024
Stanford University
2019-2023
Stanford Medicine
2021
Children's Hospital of Philadelphia
2010-2020
Spark Therapeutics (United States)
2015-2019
University of Pennsylvania
2007-2017
Philadelphia University
2013
Epigen Biosciences (United States)
2003-2006
Queen's University
2003
Ontario Veterinary College
2003
Chimeric antigen receptor-modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric receptor clinical activity acute lymphoblastic (ALL). Two children relapsed and refractory pre-B-cell ALL received infusions transduced anti-CD19 antibody a T-cell signaling molecule (CTL019 cells), at dose 1.4×10(6) 1.2×10(7) CTL019 per kilogram body weight. In both patients, expanded level that was more...
Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form the disease, LCA2, caused by mutations in retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated safety subretinal delivery recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients LCA2 had an acceptable local and systemic adverse-event profile after...
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.
The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration adeno-associated viral (AAV) vectors encoding RPE65 patients LCA2 due to mutations gene, safe and, some cases, results efficacy. We evaluated long-term (global effects on retinal/visual function) resulting from...
Demonstration of safe and stable reversal blindness after a single unilateral subretinal injection recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2) prompted us to determine whether it was possible obtain additional benefit through second administration AAV vector contralateral eye. Readministration eye carried out in three adults with Leber congenital amaurosis due mutations 1.7 3.3 years they had received their initial AAV2-hRPE65v2. Results (through 6...
PurposeTo report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector–based gene therapy for RPE65 mutation–associated inherited retinal dystrophy (IRD), including results a phase 1 follow-on study at year 4 and 3 2.DesignOpen-label clinical trial open-label, randomized, controlled trial.ParticipantsForty subjects who received 1.5×1011 vector genomes (vg) VN per eye in least during trials, 11 29 (20 original intervention [OI] 9 control/intervention...
Capsid decoys enhance the efficacy of AAV vector transduction after systemic delivery in presence neutralizing antibodies.
This study evaluated the safety and tolerability of ocular RS1 adeno-associated virus (AAV8-RS1) gene augmentation therapy to retina participants with X-linked retinoschisis (XLRS). XLRS is a monogenic trait affecting only males, caused by mutations in gene. Retinoschisin protein secreted principally outer retina, its absence results retinal cavities, synaptic dysfunction, reduced visual acuity, susceptibility detachment. phase I/IIa single-center, prospective, open-label,...
Preclinical efficacy and safety data in mice provide support for ex vivo β-globin gene correction to treat patients with sickle cell disease.
We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models RPE65 form Leber congenital amaurosis (LCA). Protein expression was by addition a modified Kozak sequence at translational start site hRPE65. Modifications AAV production delivery included use long stuffer to prevent reverse packaging from inverted-terminal repeats, co-injection with surfactant. The latter allows consistent predictable given dose vector. observed improved...
Abstract Gene transfer using adeno-associated virus (AAV) vectors has great potential for treating human disease. Recently, questions have arisen about the safety of AAV vectors, specifically, whether integration vector DNA in transduced cell genomes promotes tumor formation. This study addresses these with high-dose liver-directed AAV-mediated gene adult mouse as a model (80 AAV-injected mice and 52 controls). After 18 months follow-up, did not show significantly higher rate hepatocellular...
We show here that UV absorbance of denatured adeno-associated virus (AAV) vector provides a simple, rapid, and direct method for quantifying genomes capsid proteins in solution. determined the molar extinction coefficients protein to be 3.72 × 106 M−1 cm−1 at 260 nm 6.61 280 nm. For recombinant AAV vectors, can calculated by including predicted DNA. Since amount empty capsids purified preparations lowers A260/A280 ratio predictable manner, genome (vg) particle (cp) titers from ratio. To...
BackgroundA preventive vaccine for HIV is a crucial public health need; adeno-associated virus (AAV)-mediated antibody gene delivery could be an alternative to immunisation induce sustained expression of neutralising antibodies prevent HIV. We assessed safety and tolerability rAAV1-PG9DP, recombinant AAV1 vector encoding the PG9, broadly against HIV.MethodsThis first-in-human, proof-of-concept, double-blind, phase 1, randomised, placebo-controlled, dose-escalation trial was done at one...
Host immune responses that limit durable therapeutic gene expression and cause clinically significant inflammation remain a major barrier to broadly successful development of adeno-associated virus (AAV)-based human therapies. In this article, mechanisms humoral cellular the viral vector are discussed. A perspective is provided removal pathogen-associated molecular patterns in AAV genomes prevent generation innate danger signals following administration key strategy overcome immunological barriers.
Aggregation of recombinant AAV2 results in reduced yield during purification and may have deleterious effects on vector transduction efficiency, biodistribution immunogenicity following vivo administration. Studies to elucidate the mechanism aggregation methods prevent its occurrence are reported. In excipient screening studies, sugars sorbitol, sucrose, mannitol, trehalose, or glycerol at concentrations up 5% (w/v), surfactants Tween 80 Pluronic F68, did not aggregation. was prevented by...