The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy Vector
Open accessAbstract
Adeno-associated viruses (AAVs) are being developed as gene therapy vectors, and their efficacy could be improved by a detailed understanding of their viral capsid structures. AAV serotype 8 (AAV8) shows a significantly greater liver transduction efficiency than those of other serotypes, which has resulted in efforts to develop this virus as a gene therapy vector for hemophilia A and familial hypercholesterolemia. Pseudotyping studies show that the differential tissue tropism and transduction efficiencies exhibited by the AAVs result from differences in their capsid viral protein (VP) amino acids. Towards identifying the structural features underpinning these disparities, we report the crystal structure of the AAV8 viral capsid determined to 2.6-Å resolution. The overall topology of its common overlapping VP is similar to that previously reported for the crystal structures of AAV2 and AAV4, with an eight-stranded β-barrel and long loops between the β-strands. The most significant structural differences between AAV8 and AAV2 (the best-characterized serotype) are located on the capsid surface at protrusions surrounding the two-, three-, and fivefold axes at residues reported to control transduction efficiency and antibody recognition for AAV2. In addition, a comparison of the AAV8 and AAV2 capsid surface amino acids showed a reduced distribution of basic charge for AAV8 at the mapped AAV2 heparin sulfate receptor binding region, consistent with an observed non-heparin-binding phenotype for AAV8. Thus, this AAV8 structure provides an additional platform for mutagenesis efforts to characterize AAV capsid regions responsible for differential cellular tropism, transduction, and antigenicity for these promising gene therapy vectors.
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Cites
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“%) and AAV3 (85”
BackgroundInfluentialFunctional implications of the structure of the murine parvovirus, minute virus of mice
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Self-citationStructurally mapping the diverse phenotype of adeno-associated virus serotype 4
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“Density within the fivefold channel is consistent with the postulation that this capsid region is the site for externalization of the unique N-terminal region of VP1 for its phospholipase A2 activity and for the VP1 and VP2 nuclear localization signal sequences (19, 47).”
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Cited by
Adeno-Associated Virus (AAV) as a Vector for Gene Therapy
Naso, M. F., Tomkowicz, B., Perry, W. L., & Strohl, W. R. (2017) · BioDrugs · doi:10.1007/s40259-017-0234-5 · Cited by 1,362
The AAV Vector Toolkit: Poised at the Clinical Crossroads
Asokan, A., Schaffer, D. V., & Jude Samulski, R. (2012) · Molecular Therapy · doi:10.1038/mt.2011.287 · Cited by 465
Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector
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Self-citationStructural insight into the unique properties of adeno-associated virus serotype 9
DiMattia, M. A., Nam, H.-J., Van Vliet, K., Mitchell, M., Bennett, A., Gurda, B. L., McKenna, R., Olson, N. H., Sinkovits, R. S., Potter, M., et al. (2012) · Journal of Virology · doi:10.1128/jvi.07232-11 · Cited by 219
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Metadata
- Authors
- Nam, H.-J., Lane, M. D., Padron, E., Gurda, B., McKenna, R., Kohlbrenner, E., Aslanidi, G., Byrne, B., Muzyczka, N., Zolotukhin, S., & Agbandje-McKenna, M.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2007-11-15
- Volume
- 81
- Issue
- 22
- Pages
- 12260-12271
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2153140538
- Cited by
- 255
- References
- 10
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Nam, H.-J., Lane, M. D., Padron, E., Gurda, B., McKenna, R., Kohlbrenner, E., Aslanidi, G., Byrne, B., Muzyczka, N., Zolotukhin, S., & Agbandje-McKenna, M. (2007). Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy Vector. Journal of Virology. https://doi.org/10.1128/jvi.01304-07
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