Efficient gene delivery and selective transduction of astrocytes in the mammalian brain using viral vectors
Open accessAbstract
Astrocytes are now considered as key players in brain information processing because of their newly discovered roles in synapse formation and plasticity, energy metabolism and blood flow regulation. However, our understanding of astrocyte function is still fragmented compared to other brain cell types. A better appreciation of the biology of astrocytes requires the development of tools to generate animal models in which astrocyte-specific proteins and pathways can be manipulated. In addition, it is becoming increasingly evident that astrocytes are also important players in many neurological disorders. Targeted modulation of protein expression in astrocytes would be critical for the development of new therapeutic strategies. Gene transfer is valuable to target a subpopulation of cells and explore their function in experimental models. In particular, viral-mediated gene transfer provides a rapid, highly flexible and cost-effective, in vivo paradigm to study the impact of genes of interest during central nervous system development or in adult animals. We will review the different strategies that led to the recent development of efficient viral vectors that can be successfully used to selectively transduce astrocytes in the mammalian brain.
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AAV5 is astrocyte specific and its injection into the striatum and substantia nigra has previously demonstrated astrocyte-specific expression with no expression in neurons or microglia.
“AAV5 is astrocyte specific and its injection into the striatum and substantia nigra has previously demonstrated astrocyte-specific expression with no expression in neurons or microglia (Drinkut et al., 2012;Merienne et al., 2013).”
From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Merienne et al., 2013
The ‘Targeting astrocytes with transcription regulatory elements’ section reports astrocyte-specific expression, with no residual expression in neurons or microglia, after high-titer AAV5-gfa2-eGFP injection into the striatum or substantia nigra. But the broader statement that AAV5 itself is astrocyte-specific omits the gfa2 promoter and conflicts with the ‘Altering the entry of viral vectors’ section, which says AAV5 can also infect neurons and other cells. (LLM, conf=0.88)
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HSV Recombinant Vectors for Gene Therapy~!2009-12-17~!2010-13-31~!2010-06-17~!
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- Authors
- Merienne, N., Douce, J. L., Faivre, E., Déglon, N., & Bonvento, G.
- Affiliations
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Bonvento, Gilles
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 106-106
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3701857
- OpenAlex
- W2059670143
- Cited by
- 58
- References
- 163
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 10 · 2019: 2 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 1
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Agence Nationale de la Recherche
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A, 140945)
- Centre National de la Recherche Scientifique
- 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 › Neurology › Barrier Structure and Function Studies
- Keywords
- astrocytes, viral vectors, gene delivery, in vivo gene delivery, central nervous system development, neurological disorders, astrocyte function, animal models
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