The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy

Xie, Qing; Bu, Weishu; Bhatia, Smita; Hare, Joan; Somasundaram, Thayumanasamy; Azzi, Arezki; Chapman, Michael S.

doi:10.1073/pnas.162250899

Cited by 612Virus-based gene therapy researchEnzyme Structure and FunctionParvovirus B19 Infection Studies

The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy

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Xie, Qing, Bu, Weishu, Bhatia, Smita, Hare, Joan, Somasundaram, Thayumanasamy, Azzi, Arezki, Chapman, Michael S.·2002·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.162250899PMC PMC124927

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Abstract

The structure of the adeno-associated virus (AAV-2) has been determined to 3-A resolution by x-ray crystallography. AAV is being developed as a vector for gene therapy to treat diseases including hemophilia, cancer, and cystic fibrosis. As in the distantly related autonomous parvoviruses, the capsid protein has a beta-barrel fold, but long loops between the beta-strands share little structural homology with other parvoviruses, leading to unique surface features. Most prominent are groups of threefold-related peaks, each an intimate association of loops from two neighboring subunits. Mutations affecting cell entry and receptor binding are clustered near the positively charged side of each peak, implicating the region in attachment to the cellular receptor, heparan sulfate proteoglycan. Amino acids involved in antibody binding are in the same general vicinity. The structure will guide rational engineering of vector capsids to tailor cellular targeting and to avoid immediate neutralization by an immune system sensitized by prior exposure to AAV.

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In contrast to MVM and B19, the N termini of Vp1 and Vp2 of AAV are located within the virion.
“In contrast, the N termini of Vp1 and Vp2 of AAV are located within the virion (27, 46, 48).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [48]
Ordered DNA has yet to be discovered in the crystal structures solved for AAV, suggesting that DNA-capsid interactions may be lacking or not as important for AAV.
“However, ordered DNA has yet to be discovered in the crystal structures solved for AAV, suggesting that DNA-capsid interactions may be lacking or not as important for AAV (42, 48).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [48]

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Wobus, C. E., Hügle-Dörr, B., Girod, A., Petersen, G., Hallek, M., & Kleinschmidt, J. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.19.9281-9293.2000 · Cited by 273 · see citing works
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Laughlin, C. A., Tratschin, J.-D., Coon, H., & Carter, B. J. (1983) · Gene · doi:10.1016/0378-1119(83)90217-2 · Cited by 266 · see citing works
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Bowles, D. E., McPhee, S. W., Li, C., Gray, S. J., Samulski, J. J., Camp, A. S., Li, J., Wang, B., Monahan, P. E., Rabinowitz, J. E., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2011.237 · Cited by 400 · see citing works
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Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys
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Quantification of adeno-associated virus particles and empty capsids by optical density measurement
Sommer, J. Ü. M., Smith, P. H., Parthasarathy, S., Isaacs, J., Vijay, S., Kieran, J., Powell, S. K., McClelland, A., & Wright, J. F. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(02)00019-9 · Cited by 230 · see citing works
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Basic Biology of Adeno-Associated Virus (AAV) Vectors Used in Gene Therapy
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Wright, J. (2014) · Biomedicines · doi:10.3390/biomedicines2010080 · Cited by 219 · see citing works
Immune responses to adeno-associated virus and its recombinant vectors.
Sun, J. Y., Anand-Jawa, V, Chatterjee, S., & Wong, K. K. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302039 · Cited by 215 · see citing works
AAV Capsid Structure and Cell Interactions
Agbandje-McKenna, M., & Kleinschmidt, J. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-61779-370-7_3 · Cited by 215 · see citing works
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Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid
Vandenberghe, L. H., Wang, L., Somanathan, S., Zhi, Y., Figueredo, J., Calcedo, R., Sanmiguel, J., Desai, R. A., Chen, C. S., Johnston, J., et al. (2006) · Nature Medicine · doi:10.1038/nm1445 · Cited by 208 · see citing works
Adeno-Associated Virus Type 2 VP2 Capsid Protein Is Nonessential and Can Tolerate Large Peptide Insertions at Its N Terminus
Warrington, K. H., Gorbatyuk, O. S., Harrison, J. K., Opie, S. R., Zolotukhin, S., & Muzyczka, N. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6595-6609.2004 · Cited by 205 · see citing works
Mutational analysis of narrow pores at the fivefold symmetry axes of adeno-associated virus type 2 capsids reveals a dual role in genome packaging and activation of phospholipase A2 activity
Bleker, S., Sonntag, F., & Kleinschmidt, J. A. (2005) · Journal of Virology · doi:10.1128/jvi.79.4.2528-2540.2005 · Cited by 200 · see citing works
A conformational change in the adeno-associated virus type 2 capsid leads to the exposure of hidden VP1 N termini
Kronenberg, S., Böttcher, B., von der Lieth, C. W., Bleker, S., & Kleinschmidt, J. A. (2005) · Journal of Virology · doi:10.1128/jvi.79.9.5296-5303.2005 · Cited by 198 · see citing works
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Lochrie, M. A., Tatsuno, G. P., Christie, B., McDonnell, J. W., Zhou, S., Surosky, R., Pierce, G. F., & Colosi, P. (2006) · Journal of Virology · doi:10.1128/jvi.80.2.821-834.2006 · Cited by 201 · see citing works
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Mietzsch, M., Pénzes, J. J., & Agbandje-McKenna, M. (2019) · Viruses · doi:10.3390/v11040362 · Cited by 197 · see citing works
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AAV hybrid serotypes: improved vectors for gene delivery
Choi, V., McCarty, D., & Samulski, R. (2005) · Current Gene Therapy · doi:10.2174/1566523054064968 · Cited by 191 · see citing works
Molecular evolution of adeno-associated virus for enhanced glial gene delivery
Koerber, J. T., Klimczak, R., Jang, J.-H., Dalkara, D., Flannery, J. G., & Schaffer, D. V. (2009) · Molecular Therapy · doi:10.1038/mt.2009.184 · Cited by 181 · see citing works
Viral Strategies for Targeting the Central and Peripheral Nervous Systems
Bedbrook, C. N., Deverman, B. E., & Gradinaru, V. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-062048 · Cited by 168 · see citing works
DNA Shuffling of Adeno-associated Virus Yields Functionally Diverse Viral Progeny
Koerber, J. T., Jang, J.-H., & Schaffer, D. V. (2008) · Molecular Therapy · doi:10.1038/mt.2008.167 · Cited by 181 · see citing works
Adeno-Associated Virus Type 2 Contains an Integrin α5β1 Binding Domain Essential for Viral Cell Entry
Asokan, A., Hamra, J. B., Govindasamy, L., Agbandje-McKenna, M., & Samulski, R. J. (2006) · Journal of Virology · doi:10.1128/jvi.00843-06 · Cited by 183 · see citing works
Separate basic region motifs within the adeno-associated virus capsid proteins are essential for infectivity and assembly
Grieger, J. C., Snowdy, S., & Samulski, R. J. (2006) · Journal of Virology · doi:10.1128/jvi.02723-05 · Cited by 172 · see citing works
PEG conjugation moderately protects adeno‐associated viral vectors against antibody neutralization
Lee, G. K., Maheshri, N., Kaspar, B., & Schaffer, D. V. (2005) · Biotechnology and Bioengineering · doi:10.1002/bit.20562 · Cited by 169 · see citing works
Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning
Nonnenmacher, M., Wang, W., Child, M. A., Ren, X.-Q., Huang, C., Ren, A. Z., Tocci, J., Chen, Q., Bittner, K., Tyson, K., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.12.006 · Cited by 168 · see citing works
Tailoring the AAV vector capsid for gene therapy
Vandenberghe, L. H., Wilson, J. M., & Gao, G. (2009) · Gene Therapy · doi:10.1038/gt.2008.170 · Cited by 155 · see citing works
Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity
Paulk, N. K., Pekrun, K., Zhu, E., Nygaard, S., Li, B., Xu, J., Chu, K., Leborgne, C., Dane, A. P., Haft, A., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.09.021 · Cited by 161 · see citing works
Identification of factors that contribute to recombinant AAV2 particle aggregation and methods to prevent its occurrence during vector purification and formulation
Wright, J. F., Le, T., Prado, J., Bahr-Davidson, J., Smith, P. H., Zhen, Z., Sommer, J. M., Pierce, G. F., & Qu, G. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.02.021 · Cited by 158 · see citing works
Combinatorial engineering of a gene therapy vector: directed evolution of adeno‐associated virus
Perabo, L., Endell, J., King, S., Lux, K., Goldnau, D., Hallek, M., & Büning, H. (2006) · The Journal of Gene Medicine · doi:10.1002/jgm.849 · Cited by 136 · see citing works
Biophysical and Ultrastructural Characterization of Adeno-Associated Virus Capsid Uncoating and Genome Release
Horowitz, E. D., Rahman, K. S., Bower, B. D., Dismuke, D. J., Falvo, M. R., Griffith, J. D., Harvey, S. C., & Asokan, A. (2013) · Journal of Virology · doi:10.1128/jvi.03017-12 · Cited by 139 · see citing works
Novel adeno-associated viral vectors for retinal gene therapy.
Vandenberghe, L. H., & Auricchio, A. (2012) · Gene Therapy · doi:10.1038/gt.2011.151 · Cited by 131 · see citing works
Capsid antibodies to different adeno-associated virus serotypes bind common regions
Gurda, B. L., DiMattia, M. A., Miller, E. B., Bennett, A., McKenna, R., Weichert, W. S., Nelson, C. D., Chen, W.-J., Muzyczka, N., Olson, N. H., et al. (2013) · Journal of Virology · doi:10.1128/jvi.00622-13 · Cited by 127 · see citing works
Genetic modifications of the adeno-associated virus type 2 capsid reduce the affinity and the neutralizing effects of human serum antibodies
Huttner, N. A., Girod, A., Perabo, L., Edbauer, D., Kleinschmidt, J. A., Büning, H., & Hallek, M. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302123 · Cited by 124 · see citing works
Adeno-Associated Virus (AAV) Versus Immune Response
Rabinowitz, J., Chan, Y. K., & Samulski, R. J. (2019) · Viruses · doi:10.3390/v11020102 · Cited by 122 · see citing works
Directed evolution of adeno-associated virus for enhanced gene delivery and gene targeting in human pluripotent stem cells
Asuri, P., Bartel, M. A., Vazin, T., Jang, J.-H., Wong, T. B., & Schaffer, D. V. (2012) · Molecular Therapy · doi:10.1038/mt.2011.255 · Cited by 119 · see citing works
Structural studies of adeno-associated virus serotype 8 capsid transitions associated with endosomal trafficking
Nam, H.-J., Gurda, B. L., McKenna, R., Potter, M., Byrne, B., Salganik, M., Muzyczka, N., & Agbandje-McKenna, M. (2011) · Journal of Virology · doi:10.1128/jvi.05305-11 · Cited by 108 · see citing works
Heparin binding induces conformational changes in Adeno-associated virus serotype 2
Levy, H. C., Bowman, V. D., Govindasamy, L., McKenna, R., Nash, K., Warrington, K., Chen, W., Muzyczka, N., Yan, X., Baker, T. S., et al. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2008.12.002 · Cited by 110 · see citing works
Methods for Gene Transfer to the Central Nervous System
Kantor, B., Bailey, R. M., Wimberly, K., Kalburgi, S. N., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00003-2 · Cited by 109 · see citing works
Developing an Anion Exchange Chromatography Assay for Determining Empty and Full Capsid Contents in AAV6.2
Wang, C., Mulagapati, S. H. R., Chen, Z., Du, J., Zhao, X., Xi, G., Chen, L., Linke, T., Gao, C., Schmelzer, A. E., et al. (2019) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.09.006 · Cited by 105 · see citing works
Chemical modification of the adeno-associated virus capsid to improve gene delivery
Mével, M., Bouzelha, M., Leray, A., Pacouret, S., Guilbaud, M., Penaud-Budloo, M., Alvarez-Dorta, D., Dubreil, L., Gouin, S. G., Combal, J. P., et al. (2020) · Chemical Science · doi:10.1039/c9sc04189c · Cited by 92 · see citing works
Structural insights into adeno-associated virus serotype 5
Govindasamy, L., DiMattia, M. A., Gurda, B. L., Halder, S., McKenna, R., Chiorini, J. A., Muzyczka, N., Zolotukhin, S., & Agbandje-McKenna, M. (2013) · Journal of Virology · doi:10.1128/jvi.00867-13 · Cited by 95 · see citing works
AAV9: a potential blood-brain barrier buster
Manfredsson, F. P., Rising, A. C., & Mandel, R. J. (2009) · Molecular Therapy · doi:10.1038/mt.2009.15 · Cited by 94 · see citing works
Vector Uncoating Limits Adeno-Associated Viral Vector-Mediated Transduction of Human Dendritic Cells and Vector Immunogenicity
Rossi, A., Dupaty, L., Aillot, L., Zhang, L., Gallien, C., Hallek, M., Odenthal, M., Adriouch, S., Salvetti, A., & Büning, H. (2019) · Scientific Reports · doi:10.1038/s41598-019-40071-1 · Cited by 85 · see citing works
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20
McCraw, D. M., O’Donnell, J. K., Taylor, K. A., Stagg, S. M., & Chapman, M. S. (2012) · Virology · doi:10.1016/j.virol.2012.05.004 · Cited by 84 · see citing works
Self-citation
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Grieger, J. C., Johnson, J. S., Gurda-Whitaker, B., Agbandje-McKenna, M., & Samulski, R. J. (2007) · Journal of Virology · doi:10.1128/jvi.00580-07 · Cited by 83 · see citing works
Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR
Meyer, N. L., Hu, G., Davulcu, O., Xie, Q., Noble, A. J., Yoshioka, C., Gingerich, D. S., Trzynka, A., David, L., Stagg, S. M., et al. (2019) · eLife · doi:10.7554/elife.44707 · Cited by 83 · see citing works
Self-citation
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Lee, E. J., Guenther, C. M., & Suh, J. (2018) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2018.09.004 · Cited by 83 · see citing works
Utility of PEGylated recombinant adeno-associated viruses for gene transfer
Le, H. T., Yu, Q.-C., Wilson, J. M., & Croyle, M. A. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.07.019 · Cited by 82 · see citing works
AAV-ID: A Rapid and Robust Assay for Batch-to-Batch Consistency Evaluation of AAV Preparations
Pacouret, S., Bouzelha, M., Shelke, R., Andres-Mateos, E., Xiao, R., Maurer, A., Mevel, M., Turunen, H., Barungi, T., Penaud-Budloo, M., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.04.001 · Cited by 69 · see citing works
Site-specific PEGylated adeno-associated viruses with increased serum stability and reduced immunogenicity
Yao, T., Zhou, X., Zhang, C., Yu, X., Tian, Z., Zhang, L., & Zhou, D. (2017) · Molecules · doi:10.3390/molecules22071155 · Cited by 68 · see citing works
Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties
Hsu, H.-L., Brown, A., Loveland, A. B., Lotun, A., Xu, M., Luo, L., Xu, G., Li, J., Ren, L., Su, Q., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17047-1 · Cited by 63 · see citing works
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Oligonucleotide conjugated multi-functional adeno-associated viruses
Katrekar, D., Moreno, A. M., Chen, G., Worlikar, A., & Mali, P. (2018) · Scientific Reports · doi:10.1038/s41598-018-21742-x · Cited by 57 · see citing works
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Colón-Thillet, R., Jerome, K. R., & Stone, D. (2021) · Virology Journal · doi:10.1186/s12985-021-01555-7 · Cited by 50 · see citing works
Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes
Maersch, S., Huber, A., Büning, H., Hallek, M., & Perabo, L. (2010) · Virology · doi:10.1016/j.virol.2009.10.021 · Cited by 50 · see citing works
Induction of rapid and highly efficient expression of the human ND4 complex I subunit in the mouse visual system by self-complementary adeno-associated virus
Koilkonda, R. D. (2010) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2010.135 · Cited by 48 · see citing works
Development of patient-specific AAV vectors after neutralizing antibody selection for enhanced muscle gene transfer
Li, C., Wu, S., Albright, B., Hirsch, M., Li, W., Tseng, Y.-S., Agbandje-McKenna, M., McPhee, S., Asokan, A., & Samulski, R. J. (2016) · Molecular Therapy · doi:10.1038/mt.2015.134 · Cited by 48 · see citing works
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Jose, A., Mietzsch, M., Smith, J. K., Kurian, J., Chipman, P., McKenna, R., Chiorini, J., & Agbandje-McKenna, M. (2019) · Journal of Virology · doi:10.1128/jvi.01394-18 · Cited by 44 · see citing works
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Li, C., Hirsch, M., DiPrimio, N., Asokan, A., Goudy, K., Tisch, R., & Samulski, R. J. (2009) · Journal of Virology · doi:10.1128/jvi.00278-09 · Cited by 42 · see citing works
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“To date, the high resolution structures of several AAV serotypes, AAV1-3, 6-9, clonal isolates AAV4 and AAV5, and rhesus isolates AAVrh8 and AAVrh32, have been determined by cryo-EM and/or X-ray crystallography (DiMattia et al., 2012; Drouin et al., 2016; Govindasamy et al., 2006; Govindasamy et al., 2013; Halder et a…”
Background
Atomic structure of a rationally engineered gene delivery vector, AAV2. 5
Burg, M., Rosebrough, C., Drouin, L. M., Bennett, A., Mietzsch, M., Chipman, P., McKenna, R., Sousa, D., Potter, M., Byrne, B., et al. (2018) · Journal of Structural Biology · doi:10.1016/j.jsb.2018.05.004 · Cited by 30 · see citing works
Library Selection and Directed Evolution Approaches to Engineering Targeted Viral Vectors
Jang, J., Lim, K., & Schaffer, D. V. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21541 · Cited by 26 · see citing works
Biodistribution of adeno-associated virus type 2 with mutations in the capsid that contribute to heparan sulfate proteoglycan binding
Gorbatyuk, O. S., Warrington, K. H., Gorbatyuk, M. S., Zolotukhin, I., Lewin, A. S., & Muzyczka, N. (2019) · Virus Research · doi:10.1016/j.virusres.2019.197771 · Cited by 18 · see citing works
Deleterious effect of peptide insertions in a permissive site of the AAV2 capsid
Douar, A. M., Poulard, K., & Danos, O. (2003) · Virology · doi:10.1016/s0042-6822(03)00186-7 · Cited by 17 · see citing works
Effects of Altering Heparan Sulfate Proteoglycan Binding and Capsid Hydrophilicity on Retinal Transduction by Adeno-associated Virus
Crosson, S. M., Bennett, A., Fajardo, D., Peterson, J. J., Zhang, H., Li, W., Leahy, M. T., Jennings, C. K., Boyd, R. F., Boye, S. L., et al. (2021) · Journal of Virology · doi:10.1128/jvi.02440-20 · Cited by 16 · see citing works
Characterization of Naturally-Occurring Humoral Immunity to AAV in Sheep
Tellez, J., Van Vliet, K., Tseng, Y.-S., Finn, J. D., Tschernia, N., Almeida-Porada, G., Arruda, V. R., Agbandje-McKenna, M., & Porada, C. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075142 · Cited by 18 · see citing works

Authors: Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., & Chapman, M. S.
Affiliations: Florida State University (US)
ORCID: Bhatia, Smita
Somasundaram, Thayumanasamy
Azzi, Arezki
Chapman, Michael S.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2002-07-22
Volume: 99
Issue: 16
Pages: 10405-10410
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.162250899
PMC: PMC124927
OpenAlex: W1965786463
Cited by: 612
References: 4
Citations by year: 2026: 12 · 2025: 26 · 2024: 25 · 2023: 30 · 2022: 20 · 2021: 27 · 2020: 28 · 2019: 29 · 2018: 18 · 2017: 21 · 2016: 11 · 2015: 26 · 2014: 24 · 2013: 26 · 2012: 31
FWCI: 17.50
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
Keywords: adeno-associated virus type 2, gene therapy vectors, beta-barrel fold, threefold symmetry, receptor binding, antibody binding sites, capsid engineering, viral entry
MeSH terms: Dependovirus, Amino Acid Sequence, Antigens, Viral, Genetic Vectors, HeLa Cells, Humans, Molecular Sequence Data, Receptors, Virus, Genetic Therapy, Crystallography, X-Ray

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The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy

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