Gene delivery targeted to oligodendrocytes using a lentiviral vector: Gene delivery to oligodendrocytes
Abstract
BACKGROUND: Most leukodystrophies result from mutations in genes expressed in oligodendrocytes that may cause autonomous loss of function of cell structural proteins. Therefore, effective gene delivery to oligodendrocytes is necessary to develop future treatments. MATERIALS: To achieve this, we cloned a lentiviral vector in which the enhanced green fluorescent protein (EGFP) expression was driven by the oligodendrocyte specific 2,3-cyclic nucleotide 3-phosphodiesterase promoter. The vector was inserted into C57BL/6 neonatal mouse brain by combined intraventricular and parenchymal injections. RESULTS: Assessment of EGFP expression revealed a widespread distribution, specifically in cells of the oligodendrocyte linage, starting from postnatal day 6 (P6) in the subventricular zone and spreading through migrating oligodendrocyte precursors. By P30, it was detectable throughout the brain and persisted for at least 3 months, showing an increase both in the number of expressing cells and in intensity over time. EGFP expression was restricted to oligodendrocyte linage cells. On average, 20.3 ± 2.56% of all oligodendrocytes in different central nervous system areas were EGFP-positive, with regional variations. CONCLUSIONS: Lentiviral gene delivery using an oligodendrocyte-specific promoter may achieve widespread and long-lasting expression selectively in oligodendrocytes, offering a possibility for gene therapy in certain leukodystrophies, although the relatively low rates of oligodendrocyte transduction are a limitation that remains to be overcome.
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The 2,3-cyclic nucleotide 3-phosphodiesterase promoter has been reported to convey oligodendroglial-specific GFP reporter gene expression following lentiviral delivery to the neonatal mouse brain.
“Recently, the 2,3-cyclic nucleotide 3-phosphodiesterase promoter, first described in transgenic mice (Gravel et al., 1998), has been reported to convey oligodendroglial-specific GFP reporter gene expression following lentiviral delivery to the neonatal mouse brain (Kagiava et al., 2014).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Kagiava et al., 2014
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- Authors
- Kagiava, A., Sargiannidou, I., Bashiardes, S., Richter, J., Schiza, N., Christodoulou, C., Gritti, A., & Kleopa, K. A.
- Affiliations
- Cyprus Institute of Neurology and Genetics (CY)
- The San Raffaele Telethon Institute for Gene Therapy (IT)
- Corresponding author
- Kleopa, Kleopas A.
- ORCID
- Venue
- The Journal of Gene Medicine
- Publisher
- Wiley
- Published
- 2014-11
- Volume
- 16
- Issue
- 11-12
- Pages
- 364-373
- ISSN
- 1099-498X (ISSN-L)
- OpenAlex
- W2169776341
- Cited by
- 12
- References
- 57
- Citations by year
- 2025: 1 · 2021: 3 · 2019: 3 · 2017: 1 · 2016: 3 · 2015: 1
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Gene Medicine (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- European Leukodystrophy Association (ELA) Research Foundation (ELA 2011- 025I2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- oligodendrocytes, lentiviral vectors, gene delivery, leukodystrophy, gene therapy, oligodendrocyte precursor cells, subventricular zone, transduction efficiency, neonatal mouse brain
- MeSH terms
- Animals, Brain, Female, Genetic Vectors, Male, Mice, Inbred C57BL, Oligodendroglia, Sciatic Nerve, Genetic Therapy, Gene Expression, Lentivirus, PC12 Cells, Coculture Techniques, Green Fluorescent Proteins, Rats
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