title: Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system.
abstract: Several diseases of the nervous system are characterized by neurodegeneration and death in childhood. Conventional medicine is ineffective, but fetal or neonatal gene therapy may provide an alternative route to treatment. We evaluated the ability of single-stranded and self-complementary adeno-associated virus pseudotype 2/9 (AAV2/9) to transduce the nervous system and target gene expression to specific neural cell types following intravenous injection into fetal and neonatal mice, using control uninjected age-matched mice. Fetal and neonatal administration produced global delivery to the central (brain, spinal cord, and all layers of the retina) and peripheral (myenteric plexus and innervating nerves) nervous system but with different expression profiles within the brain; fetal and neonatal administration resulted in expression in neurons and protoplasmic astrocytes, respectively. Neither single-stranded nor self-complementary AAV2/9 triggered a microglia-mediated immune response following either administration. In summary, intravenous AAV2/9 targets gene expression to specific neural cell types dependent on developmental stage. This represents a powerful tool for studying nervous system development and disease. Furthermore, it may provide a therapeutic strategy for treatment of early lethal genetic diseases, such as Gaucher disease, and for disabling neuropathies, such as preterm brain injury.
authors: Gene Transfer Technology Group, Institute for Women's Health, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK.
authors: Ahad A
authors: AA
authors: Rahim
authors: Andrew M S
authors: AM
authors: Wong
authors: Klemens
authors: K
authors: Hoefer
authors: Suzanne M K
authors: SM
authors: Buckley
authors: Citra N
authors: CN
authors: Mattar
authors: Seng H
authors: SH
authors: Cheng
authors: Jerry K Y
authors: JK
authors: Chan
authors: Jonathan D
authors: JD
authors: Cooper
authors: Simon N
authors: SN
authors: Waddington
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002490:Central Nervous System / Q000166:cytology*; D000229:Dependovirus / Q000145:classification*; D005123:Eye; D005333:Fetus; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017933:Peripheral Nervous System / Q000166:cytology; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes
chemical_list: D049452:Green Fluorescent Proteins