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Cited by 90Virus-based gene therapy researchRNA Interference and Gene DeliveryNeurogenetic and Muscular Disorders Research

Astrocyte-selective AAV gene therapy through the endogenous GFAP promoter results in robust transduction in the rat spinal cord following injury

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Griffin, Jarred M., Fackelmeier, Barbara, Fong, Dahna M., Mouravlev, Alexander, Young, Deborah, O’Carroll, Simon J.·2019·Gene Therapy
DOI 10.1038/s41434-019-0075-6PMC PMC6760677
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Abstract

Adeno-associated viral (AAV) vectors are a promising system for transgene delivery into the central nervous system (CNS) based on their safety profile and long-term gene expression. Gene delivery to the CNS has largely been neuron centric but advances in AAV technology are facilitating the development of approaches to enable transduction of glial cells. Considering the role of astrocytes in the on-going secondary damage in spinal cord injury (SCI), an AAV vector that targets astrocytes could show benefit as a potential treatment. Transduction efficiency, transgene expression and cellular tropism were compared for the AAV serotypes AAV5, AAV9 and AAVRec2 whereby destabilised yellow fluorescent protein (dYFP) was controlled by the GFAP or the truncated GfaABC 1 D promoter. The vectors were tested in primary spinal cord astrocyte cell culture, spinal cord slice culture and an in vivo model of SCI contusion. AAV5 resulted in greater transduction efficiency, transgene expression and astrocyte tropism compared with AAV9 and AAVRec2. In a rodent model of SCI, robust transgene expression by AAV5-GFAP/GfaABC 1 D-dYFP was observed through 12 mm of spinal cord tissue and expression was largely restricted to astrocytes. Thus, AAV5-GFAP/GfaABC 1 D carries the potential as a potential gene therapy vector, particularly for transducing astrocytes in the damaged spinal cord.

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Cited by

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Authors
Griffin, J. M., Fackelmeier, B., Fong, D. M., Mouravlev, A., Young, D., & O’Carroll, S. J.
Affiliations
University of Auckland (NZ)
Corresponding author
O’Carroll, Simon J.
ORCID
Venue
Gene Therapy
Publisher
Springer Science and Business Media LLC
Published
2019-04-08
Volume
26
Issue
5
Pages
198-210
ISSN
  • 0969-7128 (ISSN-L)
  • 1476-5462
DOI
10.1038/s41434-019-0075-6
PMC
PMC6760677
OpenAlex
W2933621474
Cited by
90
References
4
Citations by year
2026: 11 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 18 · 2021: 14 · 2020: 14 · 2019: 2
FWCI
7.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Gene Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ResearchSpace (University of Auckland) (submittedVersion, cc-by)
Funders
CatWalk Spinal Cord Injury Research Trust
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
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
Keywords
adeno-associated virus vectors, GFAP promoter, spinal cord injury, AAV5, AAV9, transduction efficiency, contusion injury model, secondary damage
MeSH terms
Dependovirus, Animals, Astrocytes, Cells, Cultured, Glial Fibrillary Acidic Protein, Promoter Regions, Genetic, Spinal Cord Injuries, Genetic Therapy, Rats, Sprague-Dawley, Gene Transfer Techniques, Green Fluorescent Proteins, Rats

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