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

Abstract

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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Acknowledgements

This work was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (R01NS39071). We acknowledge David K Flaherty, Ruju Chen, Columbus Children's Research Institute Viral Vector Core Laboratory, and Columbus Children's Research Institute Histology Core Laboratory for their technical assistance. We also thank R Jude Samulski for the generous gift of the pXR1 plasmid.

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Wang, C., Wang, CM., Clark, K. et al. Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain. Gene Ther 10, 1528–1534 (2003). https://doi.org/10.1038/sj.gt.3302011

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