Atomic structure of a rationally engineered gene delivery vector, AAV2. 5
Open accessAbstract
AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 Å using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2.5 residues exchanged from AAV2 to AAV1, Q263A, T265 (insertion), N706A, V709A, and T717N, were readily interpretable. Significantly, the surface loops containing these residues adopt the AAV1 conformation indicating the importance of amino acid residues in dictating VP structure.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Capsid engineering for capsids with resistance to antibodies can be performed through rational design.
“Capsid engineering for capsids with resistance to antibodies can be performed through rational design (82 -88).”
From A versatile toolkit for overcoming AAV immunity (2022) · cites this paper as [84]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
The PyMOL Molecular Graphics System
DeLano, W. L. (2002) · Medical Entomology and Zoology · Cited by 18,147 · see citing works
SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information
Biasini, M., Bienert, S., Waterhouse, A. M., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Cassarino, T. G., Bertoni, M., Bordoli, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku340 · Cited by 4,621 · see citing works
In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy
Nelson, C. E., Hakim, C. H., Ousterout, D. G., Thakore, P. I., Moreb, E. A., Rivera, R. M. C., Madhavan, S., Pan, X., Ran, F. A., Yan, W. X., et al. (2016) · Science · doi:10.1126/science.aad5143 · Cited by 1,144 · see citing works
Dystrophin Immunity in Duchenne's Muscular Dystrophy
Mendell, J. R., Campbell, K., Rodino-Klapac, L., Sahenk, Z., Shilling, C., Lewis, S., Bowles, D., Gray, S., Li, C., Galloway, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000228 · Cited by 655 · see citing works
UCSF Chimera, MODELLER, and IMP: An integrated modeling system
Yang, Z. R., Lasker, K., Schneidman‐Duhovny, D., Webb, B., Huang, C. C., Pettersen, E. F., Goddard, T. D., Meng, E. C., Šali, A., & Ferrin, T. E. (2011) · Journal of Structural Biology · doi:10.1016/j.jsb.2011.09.006 · Cited by 637 · see citing works
The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy
Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., & Chapman, M. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162250899 · Cited by 612 · see citing works
Li, H., Fujimoto, N., Sasakawa, N., Shirai, S., Ohkame, T., Sakuma, T., Tanaka, M., Amano, N., Watanabe, A., Sakurai, H., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.10.013 · Cited by 523 · see citing works
Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector
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
Self-citationGray, S. J., Nagabhushan Kalburgi, S., McCown, T. J., & Jude Samulski, R. (2013) · Gene Therapy · doi:10.1038/gt.2012.101 · Cited by 377 · see citing works
Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy Vector
Nam, H.-J., Lane, M. D., Padron, E., Gurda, B. L., McKENNA, R. V., Kohlbrenner, E., Aslanidi, G., Byrne, B. J., Muzyczka, N., Zolotukhin, S., et al. (2007) · Journal of Virology · doi:10.1128/jvi.01304-07 · Cited by 256 · see citing works
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 · see citing works
Self-citationAAV 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
Self-citationStructurally mapping the diverse phenotype of adeno-associated virus serotype 4
Govindasamy, L., Padron, E., McKenna, R., Muzyczka, N., Kaludov, N., Chiorini, J. A., & Agbandje-McKenna, M. (2006) · Journal of Virology · doi:10.1128/jvi.01536-06 · Cited by 205 · see citing works
Self-citationLochrie, 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
Ousterout, D. G., Pérez‐Piñera, P., Thakore, P. I., Kabadi, A. M., Brown, M. T., Qin, X., Fedrigo, O. D., Mouly, V., Tremblay, J. P., & Gersbach, C. A. (2013) · Molecular Therapy · doi:10.1038/mt.2013.111 · Cited by 181 · see citing works
Structural Characterization of the Dual Glycan Binding Adeno-Associated Virus Serotype 6
Ng, R., Lakshmanan Govindasamy, A., Gurda, B. L., McKENNA, R. V., Kozyreva, O. G., Samulski, R. J., Parent, K. N., Baker, T. S., & Agbandje‐McKenna, M. (2010) · Journal of Virology · doi:10.1128/jvi.01235-10 · Cited by 143 · see citing works
Self-citationAdeno-Associated Virus Structural Biology as a Tool in Vector Development
Drouin, L. M., & Agbandje-McKenna, M. (2013) · Future Virology · doi:10.2217/fvl.13.112 · Cited by 114 · see citing works
Self-citationLerch, T. F., Xie, Q., & Chapman, M. S. (2010) · Virology · doi:10.1016/j.virol.2010.03.027 · Cited by 107 · see citing works
Li, C., Diprimio, N., Bowles, D. E., Hirsch, M. L., Monahan, P. E., Asokan, A., Rabinowitz, J., Agbandje-McKenna, M., & Samulski, R. J. (2012) · Journal of Virology · doi:10.1128/jvi.00675-12 · Cited by 96 · see citing works
Self-citationStructural 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
Self-citationGenome engineering: a new approach to gene therapy for neuromuscular disorders
Nelson, C. E., Robinson-Hamm, J. N., & Gersbach, C. A. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.126 · Cited by 71 · see citing works
Structure of neurotropic adeno-associated virus AAVrh.8
Halder, S., Vliet, K. V., Smith, J. K., Duong, T. T. P., McKENNA, R. V., Wilson, J. M., & Agbandje‐McKenna, M. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.08.017 · Cited by 62 · see citing works
Self-citationParvoviruses: Structure and Infection
Halder, S., Ng, R., & Agbandje‐McKenna, M. (2012) · Future Virology · doi:10.2217/fvl.12.12 · Cited by 53 · see citing works
Self-citationStructural Insights into Human Bocaparvoviruses
Mietzsch, M., Kailasan, S., Garrison, J., Ilyas, M., Chipman, P. R., Kantola, K., Janssen, M. E. W., Spear, J. M., Sousa, D. R., McKENNA, R. V., et al. (2017) · Journal of Virology · doi:10.1128/jvi.00261-17 · Cited by 52 · see citing works
Self-citationThe AAV-mediated and RNA-guided CRISPR/Cas9 system for gene therapy of DMD and BMD
Wang, J.-Z., Wu, P., Shi, Z.-M., Xu, Y.-L., & Liu, Z.-J. (2017) · Brain and Development · doi:10.1016/j.braindev.2017.03.024 · Cited by 41 · see citing works
The structure of AAVrh32.33, a novel gene delivery vector
Mikals, K., Nam, H.-J., Vliet, K. V., Vandenberghe, L. H., Mays, L. E., McKENNA, R. V., Wilson, J. M., & Agbandje‐McKenna, M. (2014) · Journal of Structural Biology · doi:10.1016/j.jsb.2014.03.020 · Cited by 40 · see citing works
Self-citationSpear, J. M., Noble, A. J., Xie, Q., Sousa, D. R., Chapman, M. S., & Stagg, S. M. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.09.006 · Cited by 33 · see citing works
Self-citationAtomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy
Ilyas, M., Mietzsch, M., Kailasan, S., Väisänen, E., Luo, M., Chipman, P. R., Smith, J. K., Kurian, J. J., Sousa, D. R., McKENNA, R. V., et al. (2018) · Viruses · doi:10.3390/v10010022 · Cited by 25 · see citing works
Self-citationThe advances and challenges of Gene Therapy for Duchenne Muscular Dystrophy
Tremblay, J. P. (2017) · Journal of Genetic Medicine and Gene Therapy · doi:10.29328/journal.jgmgt.1001003 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Afonine PV, Headd JJ, Terwilliger TC, Adams PD 2013. Computational Crystallography Newsletter, pp. 43– 44, Vol. 4.
Cited by
Sorted by citations
Twenty-Five Years of Structural Parvovirology
Mietzsch, M., Pénzes, J. J., & Agbandje-McKenna, M. (2019) · Viruses · doi:10.3390/v11040362 · Cited by 197 · see citing works
Self-citationAdeno-associated virus 2 bound to its cellular receptor AAVR
Zhang, R., Cao, L., Cui, M., Sun, Z., Hu, M., Zhang, R., Stuart, W. S., Zhao, X., Yang, Z., Li, X., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-018-0356-7 · Cited by 106 · see citing works
Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
Mietzsch, M., Jose, A., Chipman, P. R., Bhattacharya, N., Daneshparvar, N., McKENNA, R. V., & Agbandje‐McKenna, M. (2021) · Viruses · doi:10.3390/v13010101 · Cited by 103 · see citing works
Self-citationEngineering the AAV capsid to evade immune responses
Barnes, C., Scheideler, O. J., & Schaffer, D. V. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.01.002 · Cited by 105 · see citing works
Andari, J. E., Renaud-Gabardos, E., Tulalamba, W., Weinmann, J., Mangin, L., Pham, Q. H., Hille, S. S., Bennett, A. D., Attebi, E., Bourges, E., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn4704 · Cited by 94 · see citing works
Self-citationAAV vector development, back to the future
Suárez-Amarán, L., Song, L., Tretiakova, A. P., Mikhail, S., & Samulski, R. J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.064 · Cited by 87 · see citing works
Albright, B. H., Simon, K. E., Pillai, M., Devlin, G. W., & Asokan, A. (2019) · Journal of Virology · doi:10.1128/jvi.00332-19 · Cited by 71 · see citing works
Adeno-Associated Viruses (AAV) and Host Immunity – A Race Between the Hare and the Hedgehog
Rapti, K., & Grimm, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.753467 · Cited by 70 · see citing works
Comparative Analysis of the Capsid Structures of AAVrh.10, AAVrh.39, and AAV8
Mietzsch, M., Barnes, C., Hull, J. A., Chipman, P. R., Xie, J., Bhattacharya, N., Sousa, D. R., McKENNA, R. V., Gao, G., & Agbandje‐McKenna, M. (2019) · Journal of Virology · doi:10.1128/jvi.01769-19 · Cited by 66 · see citing works
Self-citationMietzsch, M., Smith, J. K., Yu, J. C., Banala, V., Emmanuel, S. N., Jose, A., Chipman, P. R., Bhattacharya, N., McKENNA, R. V., & Agbandje‐McKenna, M. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.10.001 · Cited by 61 · see citing works
Self-citationAdeno-Associated Virus 2 at 2.8 ang
Lou, Z. Y., & Zhang, R. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb6ih9/pdb · Cited by 66 · see citing works
A versatile toolkit for overcoming AAV immunity
Li, X., Wei, X., Lin, J., & Ou, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.991832 · Cited by 57 · see citing works
Protease-activatable adeno-associated virus vector for gene delivery to damaged heart tissue
Guenther, C. M., Brun, M. J., Bennett, A. D., Ho, M. L., Chen, W., Zhu, B., Lam, M., Yamagami, M., Kwon, S., Bhattacharya, N., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.015 · Cited by 46 · see citing works
Self-citationCryo-electron Microscopy of Adeno-associated Virus
Stagg, S. M., Yoshioka, C., Davulcu, O., & Chapman, M. S. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00936 · Cited by 47 · see citing works
Zhao, Z., Kim, J., Suja, V. C., Kapate, N., Gao, Y., Guo, J., Muzykantov, V. R., & Mitragotri, S. (2022) · Advanced Science · doi:10.1002/advs.202201293 · Cited by 34 · see citing works
Gene therapy for genetic diseases: challenges and future directions
Beibei, Q. I. E., Tuo, J., Chen, F., Ding, H., & Lyu, L. (2025) · MedComm · doi:10.1002/mco2.70091 · Cited by 37 · see citing works
Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2
Bennett, A., Keravala, A., Makal, V., Kurian, J., Belbellaa, B., Aeran, R., Tseng, Y.-S., Sousa, D., Spear, J., Gasmi, M., et al. (2020) · Journal of Structural Biology · doi:10.1016/j.jsb.2019.107433 · Cited by 33 · see citing works
“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…”
BackgroundInfluentialSelf-citationViney, L., Bürckstümmer, T., Eddington, C., Mietzsch, M., Choudhry, M. S., Henley, T., & Agbandje‐McKenna, M. (2021) · Journal of Virology · doi:10.1128/jvi.02023-20 · Cited by 25 · see citing works
Self-citationStructural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology
Mietzsch, M., McKENNA, R. V., Väisänen, E., Yu, J. C., Ilyas, M., Hull, J. A., Kurian, J. J., Smith, J. K., Chipman, P. R., Lasanajak, Y., et al. (2020) · Viruses · doi:10.3390/v12060653 · Cited by 20 · see citing works
Self-citationMietzsch, M., Hull, J. A., Makal, V., Ybargollin, A. J., Yu, J. C., McKissock, K., Bennett, A., Pénzes, J., Lins-Austin, B., Yu, Q., et al. (2022) · Journal of Virology · doi:10.1128/jvi.00335-22 · Cited by 18 · see citing works
Self-citationStructural characterization of a bat Adeno-associated virus capsid
Mietzsch, M., Li, Y., Kurian, J. J., Smith, J. K., Chipman, P. R., McKENNA, R. V., Yang, L., & Agbandje‐McKenna, M. (2020) · Journal of Structural Biology · doi:10.1016/j.jsb.2020.107547 · Cited by 17 · see citing works
Self-citationAbdul, T. Y., Hawse, G. P., Smith, J., Sellon, J. L., Abdel, M. P., Wells, J. W., Coenen, M. J., Evans, C. H., & la Vega, R. E. D. (2022) · Gene Therapy · doi:10.1038/s41434-022-00326-5 · Cited by 16 · see citing works
The amazing AAV capsids: Into the structure-verse
Hsi, J., Mietzsch, M., & McKENNA, R. V. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101629 · Cited by 8 · see citing works
Self-citationViral Vector Technologies and Strategies: Improving on Nature
Croze, R. H., Kotterman, M. A., Burns, C. H., Schmitt, C. E., Quezada, M., Schaffer, D. V., Kirn, D. H., & Francis, P. J. (2021) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000361 · Cited by 5 · see citing works
I Am Here: It Took a Global Village
Agbandje‐McKenna, M. (2021) · Annual Review of Virology · doi:10.1146/annurev-virology-091919-104940 · Cited by 5 · see citing works
Self-citationOsteoarthritis Gene Therapy: A 30‐Year Journey From Concept to Clinical Trials
Evans, C. H., Ghivizzani, S. C., & Robbins, P. D. (2026) · Journal of Orthopaedic Research® · doi:10.1002/jor.70141 · Cited by 4 · see citing works
Parambathu, A. V., Kumar, V., Khanal, O., & Lenhoff, A. M. (2025) · Molecular Therapy Advances · doi:10.1016/j.omta.2025.201656 · Cited by 1 · see citing works
Noriega, H. A., Qizhao, W., Yu, D., & Wang, X. S. (2025) · Frontiers in Artificial Intelligence · doi:10.3389/frai.2025.1559461 · Cited by 2 · see citing works
Adeno-associated virus-mediated gene therapy in central nervous system genetic disorders
Casy, W., Ling, Q., Shaffo, F. C., Sinnett, S. E., & Gray, S. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813955-4.00010-6
Adeno-associated virus-mediated gene therapy in central nervous system genetic disorders
Ling, Q., Boitnott, A., Garza, I. T., Casy, W., Shaffo, F. C., Sinnett, S. E., & Gray, S. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00007-8
- Authors
- Burg, M., Rosebrough, C., Drouin, L. M., Bennett, A., Mietzsch, M., Chipman, P., McKenna, R., Sousa, D., Potter, M., Byrne, B., Jude Samulski, R., & Agbandje-McKenna, M.
- Affiliations
- University of Florida (US)
- Florida State University (US)
- Venue
- Journal of Structural Biology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 203
- Issue
- 3
- Pages
- 236-241
- ISSN
- 1047-8477 (ISSN-L)
- PMC
- PMC9908299
- OpenAlex
- W2803869264
- Cited by
- 30
- References
- 30
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 7
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Florida State University
- University of Florida
- National Institutes of Health (1s10od018142-01)
- National Institute of General Medical Sciences (U24GM116788, R01GM082946)
- National Institute of Allergy and Infectious Diseases (R01AI072176)
- National Center for Research Resources (S10RR025080)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- AAV2/5, adeno-associated virus, gene delivery vectors, structure-guided design, AAV serotype 2, antibody escape, cryo-EM structure
- MeSH terms
- Dependovirus, Epitopes, Capsid, Genetic Vectors, Humans, Protein Binding, Genetic Therapy, Gene Transfer Techniques, Parvovirinae, Cryoelectron Microscopy, Capsid Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
