Recombinant adeno-associated virus vector: use for transgene expression and anterograde tract tracing in the CNS
Open accessAbstract
We used a recombinant adeno-associated virus vector (AAV) to deliver a foreign gene, green fluorescent protein (GFP), into mature neurons in adult rat CNS in vivo. Microinjections of AAV as small as 50 nl transduced hundreds of neurons at the injection site. There was virtually no retrograde transport as fewer than one neuron per brain was found distant from the injection site that exhibited GFP immunoreactivity. The gene product, GFP, filled the entire neuronal cytoplasmic compartment; GFP immunoreactivity was robust in cell bodies, axons, and nerve terminals. There was no tissue damage at the injection sites or pathogenicity indicated by changes in astrocytic or microglial markers. There was no inflammatory response as judged by leukocytic invasion. Gene expression in transduced cells was robust and apparently permanent: there was no evidence of phenotypic reversion up to 12 weeks following infection. AAV is an excellent vector for introducing foreign genes into mature CNS neurons. Not only might it be an ideal vehicle for gene therapy, but also the GFP-containing AAV presents a new strategy for tracing long axonal pathways in the CNS, which is difficult with current tracers (PHAL, biotinylated dextrans).
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Compared to conventional tracers which often have mixed anterograde and retrograde transport, retrograde labelling with AAV (except for certain serotypes) is generally negligible.
“Second, compared to conventional tracers which often have mixed anterograde and retrograde transport, retrograde labelling with AAV (except for certain serotypes) is generally negligible.”
From A mesoscale connectome of the mouse brain (2014) · cites this paper as [19]
AAV mediates robust fluorescent labelling of the soma and processes of infected neurons, which can be coupled with direct imaging methods for high-throughput production without additional histochemical staining steps.
“First, AAV mediates robust fluorescent labelling of the soma and processes of infected neurons, which can be coupled with direct imaging methods for high-throughput production without additional histochemical staining steps.”
From A mesoscale connectome of the mouse brain (2014) · cites this paper as [19]
AAV allows flexible molecular strategies to introduce various transgenes and to label specific neuronal populations by combining cell-type-selective Cre driver mice with AAV vectors harbouring a Cre-dependent expression cassette.
“Finally, perhaps the greatest advantage of using AAV over conventional tracers is the flexible molecular strategies that can be used to introduce various transgenes and to label specific neuronal populations by combining cell-type-selective Cre driver mice with AAV vectors harbouring a Cre-dependent expression cassette.”
From A mesoscale connectome of the mouse brain (2014) · cites this paper as [19]
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- Authors
- Chamberlin, N. L., Du, B., de Lacalle, S., & Saper, C. B.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Chamberlin, Nancy L.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 793
- Issue
- 1-2
- Pages
- 169-175
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4961038
- OpenAlex
- W2073539399
- Cited by
- 221
- References
- 14
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 8 · 2016: 10 · 2015: 12 · 2014: 8 · 2013: 16 · 2012: 9
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Florida
- National Institutes of Health (5r01ns022835-11)
- U.S. Public Health Service
- National Institute on Aging (AG21856, R01AG019597, R29AG012401)
- National Institute of Neurological Disorders and Stroke (NS 33987, R01NS033987, NS-22835)
- 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
- recombinant adeno-associated virus vectors, green fluorescent protein, axonal transport, retrograde transport, CNS gene therapy, microinjection
- MeSH terms
- Dependovirus, Animals, Axonal Transport, Brain, Cell Line, Genetic Vectors, Humans, Luminescent Proteins, Male, Neural Pathways, Recombination, Genetic, Gene Expression, Rats, Sprague-Dawley, Genes, Reporter, Transgenes, Green Fluorescent Proteins, Rats
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