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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Systemic delivery of scAAV9 in fetal macaques facilitates neuronal transduction of the central and peripheral nervous systems
Gene Therapy, Volume 20, No. 1, Year 2013
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Description
Correction of perinatally lethal neurogenetic diseases requires efficient transduction of several cell types within the relatively inaccessible CNS. Intravenous AAV9 delivery in mouse has achieved development stage-specific transduction of neuronal cell types, with superior neuron-targeting efficiency demonstrated in prenatal compared with postnatal recipients. Because of the clinical relevance of the non-human primate (NHP) model, we investigated the ability of AAV9 to transduce the NHP CNS following intrauterine gene therapy (IUGT). We injected two macaque fetuses at 0.9 G with 1 × 10 13 vg scAAV9-CMV-eGFP through the intrahepatic continuation of the umbilical vein. Robust green fluorescent protein (GFP) expression was observed for up to 14 weeks in the majority of neurons (including nestin-positive cells), motor neurons and oligodendrocytes throughout the CNS, with a significantly lower rate of transduction in astrocytes. Photoreceptors and neuronal cell bodies in the plexiform and ganglionic retinal layers were also transduced. In the peripheral nervous system (PNS), widespread transduction of neurons was observed. Tissues harvested at 14 weeks showed substantially lower vector copy number and GFP levels, although the percentage of GFP-expressing cells remained stable. Thus, AAV9-IUGT in late gestation efficiently transduces both the CNS and PNS with neuronal predilection, of translational relevance to hereditary disorders characterized by perinatal onset of neuropathology. © 2013 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Mattar, Citra Nz
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Waddington, Simon N.
United Kingdom, London
University College London
Biswas, Arijit
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Johana, Nuryanti Binti
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Fisk, N. M.
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Australia, Brisbane
Uq Centre for Clinical Research
Tan, Lay Geok
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Rahim, Ahad A.
United Kingdom, London
University College London
Buckley, Suzanne M.K.
United Kingdom, London
University College London
Lu, Jia
Singapore, Singapore City
Dso National Laboratories
Choolani, Mahesh A.
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Chan, Jerry Kok Yen
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Singapore, Singapore City
Kk Women's and Children's Hospital
Singapore, Singapore City
Duke-nus Medical School
Statistics
Citations: 42
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1038/gt.2011.216
ISSN:
14765462
Research Areas
Genetics And Genomics
Health System And Policy
Maternal And Child Health