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Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence.
Abstract
Different regions of an 8.2-kb cloned DNA segment containing the target for adeno-associated virus (AAV) integration in human chromosome 19q13-3-qter (AAVS1 locus) were subcloned in an Epstein-Barr virus-based shuttle vector and propagated as episomes in a derivative of the 293 human embryonic kidney cell line. Preferential recombination with an infecting AAV genome was assessed by measuring the frequency of recombinants among the shuttle vectors recovered in Escherichia coli. The signals which direct recombination with the AAV genome were localized to a 510-nt region at the 5' end of the 8.2-kb AAVS1 DNA. Hence, the results indicate that site-specific integration of AAV is directed by a specific DNA sequence on human chromosome 19. An unusual degree of DNA heterogeneity in the recovered vector was also associated with the 510 nt at the 5' end of AAVS1 DNA, suggesting that the AAV chromosomal integration locus may be involved in genomic instability.
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“After transduction, AAV DNA remains mostly episomal besides integrating into hotspots in mitochondrial DNA and a specific location on chromosome 19 termed AAVS1 [14,15,16].”
From Viral Delivery Systems for CRISPR (2019) · cites this paper as [15]
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- [8]Weitzman, M. D., Kyöstö, S. R. M., Kotin, R. M. & Owens, R. A. (1994) Proc. Natl. Acad. Sci. USA 91, 4808–4812.
- [18]Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M. & Danielsen, M. (1987) Proc. Natl. Acad. Sci. USA 84, 7413–7417.
- [30]Yates, J. L., Warren, N., Reisman, D. & Sugden, B. (1984) Proc. Natl. Acad. Sci. USA 81, 3806–3810.
- [29]Ponticelli, S. A. & Smith, G. R. (1992) Proc. Natl. Acad. Sci. USA 89, 227–231.
- [32]Su, W., Middleton, T., Sugden, B. & Echols, H. (1991) Proc. Natl. Acad. Sci. USA 88, 10870–10874.
Cited by
Sorted by citations
Gene therapy using adeno-associated virus vectors
Daya, S., & Berns, K. I. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-08 · Cited by 926
Self-citationViral Delivery Systems for CRISPR
Xu, C. L., Ruan, M. Z. C., Mahajan, V. B., & Tsang, S. H. (2019) · Viruses · doi:10.3390/v11010028 · Cited by 277
In vivo model of adeno-associated virus vector persistence and rescue
Afione, S. A., Conrad, C. K., Kearns, W. G., Chunduru, S., Adams, R., Reynolds, T. C., Guggino, W. B., Cutting, G. R., Carter, B. J., & Flotte, T. R. (1996) · Journal of Virology · doi:10.1128/jvi.70.5.3235-3241.1996 · Cited by 223
Adeno-Associated Virus Integration: Virus versus Vector
Smith, R. H. (2008) · Gene Therapy · doi:10.1038/gt.2008.55 · Cited by 178
Adeno-associated Virus: A Key to the Human Genome?
Henckaerts, E., & Linden, R. M. (2010) · Future Virology · doi:10.2217/fvl.10.48 · Cited by 71
Chanda, D., Hensel, J., Higgs, J., Grover, R., Kaza, N., & Ponnazhagan, S. (2017) · Genes · doi:10.3390/genes8090232 · Cited by 19
McAlister, V. J., & Owens, R. A. (2010) · Virology Journal · doi:10.1186/1743-422x-7-218 · Cited by 5
Metadata
- Authors
- Giraud, C., Winocour, E., & Berns, K. I.
- Affiliations
- Department of Microbiology, Hearst Microbiology Research Center, Cornell University Medical College, New York, NY 10021.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-10-11
- Volume
- 91
- Issue
- 21
- Pages
- 10039-10043
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 117
- References
- 0
- Language
- en
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