Intravenous Administration of Self-complementary AAV9 Enables Transgene Delivery to Adult Motor Neurons

Therapeutic gene delivery to the whole spinal cord is a major challenge for the treatment of motor neuron (MN) diseases. Systemic administration of viral gene vectors would provide an optimal means for the long-term delivery of therapeutic molecules from blood to the spinal cord but this approach is...

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Bibliographic Details
Published in:Molecular therapy 2009-07, Vol.17 (7), p.1187-1196
Main Authors: Duque, Sandra, Joussemet, Béatrice, Riviere, Christel, Marais, Thibaut, Dubreil, Laurence, Douar, Anne-Marie, Fyfe, John, Moullier, Philippe, Colle, Marie-Anne, Barkats, Martine
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Amyotrophic lateral sclerosis
Animals
Animals, Newborn
Brain
Cats
Enzyme-Linked Immunosorbent Assay
Female
Gene therapy
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Genomes
Immunohistochemistry
Infusion Pumps
Life Sciences
Mice
Mice, Inbred C57BL
Motor Neuron Disease - therapy
Neurons
Original
Pregnancy
Spinal cord
Spinal Cord - metabolism
Transduction, Genetic - methods
Vascular Endothelial Growth Factor A - metabolism
Vectors (Biology)
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Summary:Therapeutic gene delivery to the whole spinal cord is a major challenge for the treatment of motor neuron (MN) diseases. Systemic administration of viral gene vectors would provide an optimal means for the long-term delivery of therapeutic molecules from blood to the spinal cord but this approach is hindered by the presence of the blood–brain barrier (BBB). Here, we describe the first successful study of MN transduction in adult animals following intravenous (i.v.) delivery of self-complementary (sc) AAV9 vectors (up to 28% in mice). Intravenous MN transduction was achieved in adults without pharmacological disruption of the BBB and transgene expression lasted at least 5 months. Importantly, this finding was successfully translated to large animals, with the demonstration of an efficient systemic scAAV9 gene delivery to the neonate and adult cat spinal cord. This new and noninvasive procedure raises the hope of whole spinal cord correction of MN diseases and may lead to the development of new gene therapy protocols in patients.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2009.71