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Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo
Abstract
Adeno-associated virus (AAV) is a promising gene vector based on a single-stranded (ss) DNA virus. Its transgene expression requires the conversion of ssDNA to double-stranded (ds) genome, a slow process responsible for the delayed transduction and occasional inefficiency. By mutating the inverted terminal repeat, we have made novel AAV vectors that predominantly package the self-complementary dsDNA genome. The dsAAV consistently demonstrated superior and accelerated transduction in vitro and in vivo. Dramatic increases in transgene expression were observed in most of the cell lines examined, including B16 melanoma and 3LL lung cancer that are difficult to be transduced by the conventional ssAAV vectors. Similar increases were also observed in vivo in a variety of tissues including muscle and liver. The dsAAV transduced a vast majority of the hepatocytes for more than 6 months, while the ssAAV transduced only a small fraction. In addition to circumventing the requirement for DNA synthesis, the dsAAV exhibited higher in vivo DNA stability and more effective circularization than the ssAAV, suggesting potential molecular mechanisms for the faster, stronger and prolonged transgene expression.
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“AAV vectors contain single-stranded DNA (ssDNA), which must be made transcriptionally active via the conversion into a double-stranded template (dsDNA) [18].”
From Viral Delivery Systems for CRISPR (2019) · cites this paper as [18]
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Adeno-associated virus vector as a platform for gene therapy delivery
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Metadata
- Authors
- Wang, Z., Ma, H.-I., Li, J., Sun, L., Zhang, J., & Xiao, X.
- Venue
- Gene Therapy
- Published
- 2003-11-17
- Volume
- 10
- Issue
- 26
- Pages
- 2105-2111
- ISSN
- 0969-7128
- 1476-5462
- Cited by
- 367
- References
- 6
- Language
- en
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- Wang, Z., Ma, H.-I., Li, J., Sun, L., Zhang, J., & Xiao, X. (2003). Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo. Gene Therapy. https://doi.org/10.1038/sj.gt.3302133