ArticleMolecular therapy. Methods & clinical development2016
Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Base editing rescues a hereditary motor neuron disease in mouse and patient-derived iPSC organoid models.Molecular therapy. Advances · 2026Article
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- Subpial transplantation of adipose-derived stem cells alleviates paraplegia in a rat model of aortic occlusion/reperfusion-induced spinal cord infarction.Regenerative therapy · 2024Article
- Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.Nature neuroscience · 2024Article
- A perspective: neuraxial therapeutics in pain management: now and future.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Protein and Gene Delivery Systems for Neurodegenerative Disorders: Where Do We Stand Today?Pharmaceutics · 2022Review
- Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Adeno-Associated Viral Vectors as Versatile Tools for Neurological Disorders: Focus on Delivery Routes and Therapeutic Perspectives.Biomedicines · 2022Review
- AAV gene therapy for Tay-Sachs disease.Nature medicine · 2022Article
- Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Glial-Neuronal Interactions in Pathogenesis and Treatment of Spinal Cord Injury.International journal of molecular sciences · 2021Review
- Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.International journal of molecular sciences · 2021Review
- Review
- Gene therapy for neurodegenerative disorders: advances, insights and prospects.Acta pharmaceutica Sinica. B · 2020Review
- Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats.Stem cells translational medicine · 2020Article
- Disease Modeling and Therapeutic Strategies in CMT2A: State of the Art.Molecular neurobiology · 2019Review
- Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation.Frontiers in neuroanatomy · 2019Review
- Gene therapy for neurological disorders: progress and prospects.Nature reviews. Drug discovery · 2018Review
- High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 5 countries.
Funding
Abstract
Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.