Guest Editors
Elizabeth A. Ottinger
NIH/NCATS
Dr. Ottinger received her PhD in Chemistry from the University of Minnesota and completed her postdoctoral training at the Joslin Diabetes Center of Harvard Medical School. Before joining NCATS in 2010, she was in the Vaccine Development Department at Merck Research Laboratories. At NCATS, she was Deputy Director for Programs & and Head of Project Management in the Therapeutic Development Branch (TDB), and her team managed a portfolio of IND-enabling projects focusing on rare and neglected diseases. In 2022, Dr. Ottinger became the Acting Director of TDB in the Division of Preclinical Innovation. Over the past 13 years, she has led multiple collaborative projects involving public-private partnerships to advance small molecules and biotherapeutics through pre-clinical and early clinical development, contributing to six INDs and one drug approval. Her research interests are developing tools and platforms to increase the efficiency of therapeutic development processes.
Rodica Stan
NIH/NCATS
Dr. Stan received her PhD in Biochemistry/Molecular Biology from Rutgers University and completed her postdoctoral training at Memorial Sloan Kettering Cancer Center. Before joining NCATS, she worked in translational research at City of Hope National Medical Center in cell and gene therapy in oncology and HIV/AIDS and small molecules and vaccines for other diseases. Since 2022, she has been a Senior Scientific Project Manager in the Therapeutic Development Branch within NCATS’ Division of Preclinical Innovation. She manages projects focused on gene therapy, such as the AAV-based Platform Vector Gene Therapy (PaVe-GT), small-molecule drug development and clinical testing for rare or neglected diseases. Her goal is to bring potential therapies more quickly to patients affected by rare diseases by implementing forward-thinking translational research strategies and clinical research operations.
Charles P. Venditti
NIH/NHGRI
Dr. Venditti completed his MD, PhD at Penn State University in 1996. After his pediatrics residency at Massachusetts General Hospital and a clinical and biochemical genetics fellowship at Children's Hospital of Philadelphia, he joined the NHGRI intramural research program and is currently a Senior Investigator, Chief of the Metabolic Medicine Branch, and Head of the Organic Acid Research Section at NHGRI. As attending physician at the Mark O. Hatfield Clinical Center at NIH, Dr. Venditti has initiated a translational research program to study the natural history and clinical phenotype(s) of the hereditary methylmalonic acidemias (MMA), cobalamin metabolic disorders, and propionic acidemia. His laboratory investigations focus on the development of experimental systems to study the genetics, genomics, and biochemistry of organic acid metabolism in model organisms, disease pathophysiology, and genomic therapies, including AAV gene therapy, as treatments for this group of metabolic disorders.
Carsten G. Bonnemann
NIH/NINDS
Dr. Bönnemann received his MD from Freiburg University and the habilitation from Göttingen University, Germany. After completing his pediatric training in Germany, residency in pediatric neurology at Massachusetts General Hospital, and postdoctoral work at Children's Hospital Boston working on the molecular genetics of muscular dystrophy, he joined the Children's Hospital of Philadelphia in 2002 as Co-Director of the Neuromuscular Program and Director of the Neurogenetics Clinic. In 2010, he joined NINDS as Senior Investigator and Chief of the Neuromuscular and Neurogenetic Disorders of Childhood Section. Dr. Bönnemann's laboratory and clinical research focus on the clinical characterization and the genetic/genomic and molecular mechanisms of early onset neuromuscular and neurogenetic disease (congenital muscular dystrophies and myopathies, and congenital disorders of nerve and neuromuscular junction) to develop strategies for molecular-based and gene-directed treatments, from preclinical investigations to clinical trials. The team has defined the natural history and outcome measures in giant axonal neuropathy and initiated the first intrathecal AAV9-mediated gene transfer trial in humans for this condition.
Collection Overview
A significant treatment gap exists, given that around 10,000 rare diseases impact 25 to 30 million individuals in the United States, with less than 10% of these conditions having approved therapeutic solutions. The majority of rare diseases (~80%) are caused by single-gene defects, making them potential targets for adeno-associated virus (AAV)-based gene therapies.
This Methods Collection combines a range of techniques established in the preclinical development of AAV gene therapies in both wild-type and animal disease models. These techniques include retro-orbital delivery to neonate and adult mice, facial temporal vein and intraperitoneal injection in neonate mice, and adult tail vein injection. Some of these methods are potentially adaptable to other gene therapies and may expedite the development of treatments for rare diseases.
Articles
Consistent Delivery of Adeno-Associated Virus via Lateral Tail-Vein Injection in Adult Mice
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Cited by 1
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2024
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Fady Guirguis1,2, Véronique Bolduc1, Matthew J. Slarve3, Haiyan Zhou4,5, Francesco Muntoni2,4, Carsten G. Bönnemann1
1Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 2The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, 3Department of Molecular Microbiology and Immunology, University of Southern California, 4NIHR Great Ormond Street Hospital Biomedical Research Centre, 5Genetics and Genomic Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London
Abstracts
Cardiovascular gene transfer in mice using systemic delivery of targeted AAV vectors
Oliver Mueller*1
1University Hospital Schleswig-Holstein, Campus Kiel
An optimized protocol to successfully and consistently deliver adeno-associated virus via tail vein injection in adult mice
Fady Guirguis1,
Veronique Bolduc1,
Haiyan Zhou2,
Francesco Muntoni3,
Carsten Bonnemann*1
1Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA,
2NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK............................. Genetics and Genomic Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK,
3The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK ................................................. NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
Systemic delivery of gene therapy vectors via the facial temporal vein in murine neonates
Jachinta Rooney1
1NINDS
Low Intensity Aerobic Exercise to Improve Systemic AAV9 Efficacy
Jennifer Tinklenberg1,
Sean Mulcahy1,
Venessa Agyapong1,
W Todd Cade2,
Christina Pacak*1
1Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA,
2Duke University School of Medicine, Physical Therapy Division, Durham, NC
Systemic delivery of AAV gene therapy into neonatal mice using intraperitoneal injections
Yin Dong*1
1University of Oxford
Route Matters : Neonatal ICV Outperforms Systemic Delivery for Widespread and Durable CNS Targeting in Mice
Ophelie Vacca*1
1Université Paris-Saclay, UVSQ, IMPROVE, 78180, MONTIGNY Le BRETONNEUX, France