Oligodendrocyte-specific gene expression in mouse brain: Use of a myelin-forming cell type-specific promoter in an adeno-associated virus

Chen, Hong; McCarty, Douglas M.; Bruce, A. Gregory; Suzuki, Kazuyuki; Suzuki, Kinuko

doi:10.1002/(sici)1097-4547(19990215)55:4<504::aid-jnr10>3.0.co;2-0

Cited by 61 publications

(31 citation statements)

References 29 publications

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“…12 Alternatively, rAAV2 transduction of astrocytes might require a multiplicity of infection that could only be reached at the site of vector administration or the use of glial-specific promoters. 36 Our finding of rAAV2-transduced astrocytes near the needle track (a site of astrocyte activation and high multiplicity of infection) does not differentiate between these possibilities. In the rAAV1-injected mice, a different pattern of transduction was observed.…”

Section: Resultsmentioning

confidence: 88%

Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain

Wang²,

et al. 2003

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Recombinant adeno-associated virus serotype 2 (rAAV2) vectors have shown promise as therapeutic agents for neurologic disorders. However, intracerebral administration of this vector leads to preferential transduction of neurons and a restricted region of transgene expression. The recently developed rAAV vectors based upon nonserotype 2 viruses have the potential to overcome these limitations. Therefore, we directly compared a rAAV type 1 to a type 2 vector in the murine brain. The vectors were engineered to carry identical genomes (AAV2 terminal repeat elements flanking an enhanced green fluorescent protein expression cassette) and were administered by stereotaxic-guided intracerebral injection. We found that the rAAV1 vector (rAAV1-GFP) had a 13-to 35-fold greater transduction efficiency than that of the rAAV2 vector (rAAV2-GFP). Also, rAAV1-transduced cells were observed at a greater distance from the injection site than rAAV2-transduced cells. Neurons were the predominant cell type transduced by both vector types. However, in contrast to rAAV2-GFP, rAAV1-GFP was capable of transducing glial and ependymal cells. Thus, rAAV1-based vectors have biologic properties within the brain distinct from that of rAAV2. These differences might be capitalized upon to develop novel gene transfer strategies for neurologic disorders.

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Section: Resultsmentioning

confidence: 88%

Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain

Wang²,

et al. 2003

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“…However, this assay is biased toward cells in which the CMV promoter is active, and may favor neurons over other cell types such as oligodendrocytes. 12,13 We have also used the scAAV vectors to investigate the limits of rAAV transduction in the liver. Previous studies have shown that hepatocytes are not efficiently transduced by rAAV, the limiting factor apparently being the conversion of the single-stranded vector DNA to duplex by the liver cells.…”

Section: Tr Mutant For Self-complementary Aav Dm Mccarty Et Almentioning

confidence: 99%

Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo

et al. 2003

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An important limitation of recombinant adeno-associated virus (rAAV) vector efficiency is the requirement of hostcell-mediated synthesis of double-stranded DNA from the single-stranded genome. We have bypassed this step in a specialized self-complementary rAAV (scAAV) vector, by utilizing the tendency of AAV to package DNA dimers when the replicating genome is half the length of the wild type (wt). To produce these vectors efficiently, we have deleted the terminal resolution site (trs) from one rAAV TR, preventing the initiation of replication at the mutated end. These constructs generate single-stranded, inverted repeat genomes, with a wt TR at each end, and a mutated TR in the middle. After uncoating, the viral DNA folds through intramolecular base pairing within the mutant TR, which then proceeds through the genome to form a double-stranded molecule. We have used the scAAV to investigate barriers to rAAV transduction in the mouse liver, muscle and brain. In each tissue, scAAV was characterized by faster onset of gene expression and higher transduction efficiency. This study confirms earlier predictions that complementary-strand DNA synthesis is the primary barrier to rAAV-2 transduction. The scAAV is unaffected by this barrier, and provides an extremely efficient vector for gene transfer into many types of cells in vivo.

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“…21 Importantly, there are many different AAV serotypes available that could be used to transduce other cell types of the nervous system (Fig. 1A) including astrocytes (preferably transduced by serotypes 5 and 8 22,23 ), microglia (preferably transduced by serotype 5 24 ) and oligodendrocytes (preferably transduced by serotype 2 24,25 ), and even selective subpopulations of neurons of the brain. 22 These viruses are not pathogenic, they do not induce an immune or inflammatory response, they are maintained as episomal DNA and the expression of the transgene can last for months and even years.…”

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confidence: 99%

A new method to measure autophagy flux in the nervous system

2014

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Oligodendrocyte-specific gene expression in mouse brain: Use of a myelin-forming cell type-specific promoter in an adeno-associated virus

Cited by 61 publications

References 29 publications

Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain

Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain

Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo

A new method to measure autophagy flux in the nervous system

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