ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
A Comprehensive Map of CNS Transduction by Eight Recombinant Adeno-associated Virus Serotypes Upon Cerebrospinal Fluid Administration in Pigs.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- A single dose of a vectorized mAb targeting TDP-43 potently inhibits the neuropathology in a model of ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Anti-amyloid treatment is broadly effective in neuronopathic mucopolysaccharidoses and synergizes with gene therapy in MPS-IIIA.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- 2-Photon imaging of fluorescent proteins in living swine.Scientific reports · 2023Article
- Pre-clinical delivery of gene therapy products to the cerebrospinal fluid: challenges and considerations for clinical translation.Frontiers in molecular neuroscience · 2023Review
- Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal.Molecular therapy. Methods & clinical development · 2021Article
- Intra-cisterna magna delivery of an AAV vector with the GLUT1 promoter in a pig recapitulates the physiological expression of SLC2A1.Gene therapy · 2021Article
- Enhancing the Therapeutic Potential of Sulfamidase for the Treatment of Mucopolysaccharidosis IIIA.Molecular therapy. Methods & clinical development · 2019Article
- Review
- Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches.Italian journal of pediatrics · 2018Review
- Behavioral Assessment of Vision in Pigs.Journal of the American Association for Laboratory Animal Science : JAALAS · 2018Article
- Development of Intrathecal AAV9 Gene Therapy for Giant Axonal Neuropathy.Molecular therapy. Methods & clinical development · 2018Article
- Gene therapy for Mucopolysaccharidoses.Molecular genetics and metabolism · 2018Review
- Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets.PloS one · 2016Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Cerebrospinal fluid administration of recombinant adeno-associated viral (rAAV) vectors has been demonstrated to be effective in delivering therapeutic genes to the central nervous system (CNS) in different disease animal models. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency, and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39, and rh.43 delivered into the cisterna magna of wild-type pigs. rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested. Moreover, rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful preclinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases.
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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.