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High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors

Ahmed, SG; Waddington, SN; Boza-Morán, MG; Yáñez-Muñoz, RJ; (2018) High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors. Journal of Controlled Release , 273 pp. 99-107. 10.1016/j.jconrel.2017.12.029. Green open access

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Abstract

Integration-deficient lentiviral vectors (IDLVs) are promising gene delivery tools that retain the high transduction efficiency of standard lentiviral vectors, yet fail to integrate as proviruses and are instead converted into episomal circles. These episomes are metabolically stable and support long-term expression of transgenes in non-dividing cells, exhibiting a decreased risk of insertional mutagenesis. We have embarked on an extensive study to compare the transduction efficiency of IDLVs pseudotyped with different envelopes (vesicular stomatitis, Rabies, Mokola and Ross River viral envelopes) and self-complementary adeno-associated viral vectors, serotype-9 (scAAV-9) in spinal cord tissues after intraspinal injection of mouse embryos (E16). Our results indicate that IDLVs can transduce motor neurons (MNs) at extremely high efficiency regardless of the envelope pseudotype while scAAV9 mediates gene delivery to ~40% of spinal cord motor neurons, with other non-neuronal cells also transduced. Long-term expression studies revealed stable gene expression at 7months post-injection. Taken together, the results of this study indicate that IDLVs may be efficient tools for in utero cord transduction in therapeutic strategies such as for treatment of inherited early childhood neurodegenerative diseases.

Type: Article
Title: High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jconrel.2017.12.029
Publisher version: http://doi.org/10.1016/j.jconrel.2017.12.029
Language: English
Additional information: Copyright © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Keywords: In utero gene delivery, Integration-deficient lentiviral vectors (IDLV), Pseudotyping, Spinal cord
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10043651
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