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 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.
CNRS FRE-GENETHON, Evry, France.
Sandra
S
Duque
Béatrice
B
Joussemet
Christel
C
Riviere
Thibaut
T
Marais
Laurence
L
Dubreil
Anne-Marie
AM
Douar
John
J
Fyfe
Philippe
P
Moullier
Marie-Anne
MA
Colle
Martine
M
Barkats
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D002415:Cats; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D007150:Immunohistochemistry; D007260:Infusion Pumps; D051379:Mice; D008810:Mice, Inbred C57BL; D016472:Motor Neuron Disease / Q000628:therapy; D011247:Pregnancy; D013116:Spinal Cord / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A