The DOI matches its Crossref record; 192 of the 195 references it cites were found in a registry or an index.
AAV Capsid Structure and Cell Interactions
Abstract
The Adeno-associated viruses (AAVs) are not associated with any diseases, and their ability to package non-genomic DNA and to transduce different cell/tissue populations has generated significant interest in understanding their basic biology in efforts to improve their utilization for corrective gene delivery. This includes their capsid structure, cellular tropism and interactions for entry, uncoating, replication, DNA packaging, capsid assembly, and antibody neutralization. The human and nonhuman primate AAVs are clustered into serologically distinct genetic clade and serotype groups, which have distinct cellular/tissue tropisms and transduction efficiencies. These properties are highly dependent upon the AAV capsid amino acid sequence, their capsid structure, and their interactions with host cell factors, including cell surface receptors, co-receptors, signaling molecules, proteins involved in host DNA replication, and host-derived antibodies. This chapter reviews the current structural information on AAV capsids and the capsid viral protein regions playing a role in the cellular interactions conferring an infective phenotype, which are then used to annotate the functional regions of the capsid. Based on the current data, the indication is that the AAVs, like other members of the Parvoviridae and other ssDNA viruses that form a T = 1 capsid, have evolved a multifunctional capsid with conserved core regions as is required for efficient capsid trafficking, capsid assembly, and genome packaging. Disparate surface loop structures confer differential receptor recognition and are involved in antibody recognition. The role of structural regions in capsid uncoating remains to be elucidated.
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In the citing paper
“The unique topology of the AAV capsid confers cellular tropism by differential receptor binding.”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [18]
In the citing paper
“The first step of AAV transduction entails AAV binding to a primary receptor and co-receptor on the cell surface.18”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [18]
In the citing paper
“The AAV capsids have nine variable regions surrounded by conserved regions where the variable regions form loops and clusters on the exterior of the capsid.18–19”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [18]
In the citing paper
“These protrusions are formed from interdigitating loops from two VPs and have the most extensive VP–VP interactions [23,24].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [24]
In the citing paper
“This region has the least number of VP–VP interface interactions and represents the thinnest region of the virus capsid shell [23,24].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [24]
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“Discussion The transduction efficiency of rAAV is largely depended on the cellular internalization and the following downstream events after the internalization of rAAV [42, 43].”
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“However, the efficacy of rAAVs is largely determined by molecular interactions between the capsid and the target cell surface receptors [32], with subsequent downstream events after particle internalization [33].”
BackgroundTaking a Hint from Structural Biology: To Better Understand AAV Transport across the BBB
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“Therefore, extensive research efforts have been focused on elucidating the structural determinants of various AAV capsids that are required for specific tissue tropism and immunogenicity.(8,9) Furthermore, these insights into the structural biology of natural AAV capsids can facilitate capsid engineering to develop sa…”
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Dou, D., Lu, J., Chen, X., & Zhang, X. (2025) · Pharmaceutical Research · doi:10.1007/s11095-025-03931-2 · Cited by 4
“The AAV capsid functions as a protective protein that encases the virus, safeguarding the nucleic acid payload from immune responses while demonstrating viral vector tropism for targeted site expression [13–15].”
Directed evolution of novel AAV capsids for enhanced delivery to mouse and human Schwann cells
Carneiro, A. D., Nisanov, A. M., Lee, H., & Schaffer, D. V. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102928 · Cited by 3
“This VP1 unique region plays a role in endosomal escape and nuclear localization, 26 which may underlie the observed differences in transduction efficiency.”
An Overview of rAAV Vector Product Development for Gene Therapy
Snyder, R. O. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-1-4939-3228-3_2 · Cited by 4
Gene Therapy: Use of Viruses as Vectors
Nance, M. E., & Duan, D. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.95711-8 · Cited by 3
Identification of a novel neutralization epitope in rhesus AAVs
Dagotto, G., Fisher, J. L., Li, D., Li, Z., Jenni, S., Li, Z., Tartaglia, L. J., Abbink, P., & Barouch, D. H. (2024) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2024.101350 · Cited by 3
“32 Our models fi t the electron density maps well, particularly for the core of the structure (Figure 5C).”
Daniel, H. D. J., Farzana, J., Kannangai, R., Kumar, S., Lakshmi, K. M., Jashal, C. B., Dhamne, H., Lahoti, V., Kanjwani, D., Abraham, A., et al. (2025) · Human Gene Therapy · doi:10.1177/10430342251366208 · Cited by 2
HUH endonuclease-mediated DNA–protein conjugates: sequence-specific tools and cellular applications
Huang, X., Li, H., Du, J., Xie, W., Liu, Y., Lin, Y., & Xing, H. (2025) · Chemical Communications · doi:10.1039/d5cc04628a · Cited by 3
Tissue‐specific gene delivery approaches
Nasr, S. S., Cheema, Y., Stern, A., Tabah, O., Poore, S., & Duncan, G. A. (2026) · Bioengineering & Translational Medicine · doi:10.1002/btm2.70125 · Cited by 3
Gene therapy targeting the blood-brain barrier
Körbelin, J., Pereira, A. A., & Schwaninger, M. (2024) · Vitamins and hormones · doi:10.1016/bs.vh.2024.03.001 · Cited by 2
Hoyle, B., Bello, D., Hill, J., Das, S., & Kim, J. (2025) · Current Gene Therapy · doi:10.2174/0115665232369708250327081305 · Cited by 2
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“Numerous evidence has been collected to provide information about the tropism, or preference to transduce, of viruses used in gene therapy, including naturally occurring and modifi ed AAVs [ 11 , 21 – 23 ].”
BackgroundNash, K. R., Cárdenas‐Aguayo, M. D. C., Berg, M. J., & Marks, N. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.02.008 · Cited by 2
Gene Therapy for X-Linked Myotubular Myopathy
Dupont, J.-B., Lawlor, M. W., & Childers, M. K. (2019) · Springer eBooks · doi:10.1007/978-3-030-03095-7_32 · Cited by 2
Development of Next-Generation Muscle Gene Therapy AAV Vectors
Nance, M. E., & Duan, D. (2019) · Springer eBooks · doi:10.1007/978-3-030-03095-7_11 · Cited by 2
Virus-assisted directed evolution of enhanced suppressor tRNAs in mammalian cellsPreprint
Kelemen, R. E., Jewel, D., Huang, R. L., Zhu, Z., Cao, X., Pasha, M., Anthony, J. S., van Opijnen, T., & Chatterjee, A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.21.477302 · Cited by 2
Vetter, J., Kley, M., Eichwald, C., & Fraefel, C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.10.642135 · Cited by 1
Altering VP1 and VP2 expression in trans affects the transduction efficiency of AAV9
Efremov, M. K., Galieva, A., Brovin, A. N., Mesonzhnik, N. V., Afonin, M., Subcheva, E. N., & Karabelsky, A. V. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1753246 · Cited by 1
Gene-sized editing for the therapy of genetic diseases
Padureanu, T., Cocoş, R., Matache, I., & Bucur, O. (2026) · Functional & Integrative Genomics · doi:10.1007/s10142-026-01823-1 · Cited by 2
Pan, Y., Zhong, Y., Chen, H., Zhang, Y., Dai, Z., Chen, J., Tan, K., Chen, X., Qiu, D., Sheng, L., et al. (2026) · Molecular Therapy Advances · doi:10.1016/j.omta.2026.201725 · Cited by 1
“21 Effective viral transduction requires transgene expression, making the detection of capsids or vector genomes insufficient for confirming successful transduction.”
Gene Therapy of CNS Disorders Using Recombinant AAV Vectors
Murlidharan, G., Samulski, R. J., & Asokan, A. (2016) · Springer eBooks · doi:10.1007/978-1-4899-7654-3_2 · Cited by 1
Viral Vectors for Muscle Gene Therapy
Wang, D., Brown, A., & Gao, G. (2019) · Springer eBooks · doi:10.1007/978-3-030-03095-7_10 · Cited by 1
Yue, P., Zhong, Y., Chen, H., Zhang, Y., Dai, Z., Chen, J., Tan, K., Chen, X. B., Qiu, D., Sheng, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.19.654800 · Cited by 1
UNDERSTANDING THE SOLUTION-PHASE BIOPHYSICS AND CONFORMATIONAL DYNAMICS OF VIRUS CAPSIDS
Rayaprolu, V. (2013) · Montana State University ScholarWorks (Montana State University)
Treating Hemophilia by Gene Therapy
Porada, C. D., Ignacio, G., Atala, A., & Almeida-Porada, G. D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800548-4.00012-7
Parvoviridae: General Features☆
Cotmore, S. F., & Tattersall, P. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.02641-6
Serotype 8 Capsid of Adeno-Associated Virus Mapping a Neutralizing Epitope onto the
Agbandje‐McKenna, M., Baker, T. S., Kleinschmidt, J. A., Naumer, M., Olson, N. H., Ng, R., Gurda, L., Raupp, C., & Popa-Wagner, R. (2012)
Self-citationBiology of AAV Vectors in the Central Nervous System
Murlidharan, G. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/cr64-be62
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
Xu, J., Wang, B., & Song, L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-820007-0.00025-8 · Cited by 1
Digital Droplet PCR Method for the Quantification of AAV Transduction Efficiency in Murine Retina
Okan, I. C. T., Ahmadian, M., Tutuncu, Y., Altay, H. Y., & Ağca, C. (2021) · Journal of Visualized Experiments · doi:10.3791/63038
Kick, G. R. (2021) · MOspace Institutional Repository (University of Missouri) · doi:10.32469/10355/88127
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Parvovirus Vectors: The Future of Gene Therapy
Gupta, M. (2022) · Veterinary medicine and science · doi:10.5772/intechopen.105085
Metadata
- Authors
- Agbandje-McKenna, M., & Kleinschmidt, J.
- Affiliations
- German Cancer Research Center (DE)
- Venue
- Methods in Molecular Biology
- Publisher
- Humana Press
- Published
- 2011-09-27
- Volume
- 807
- Pages
- 47-92
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- OpenAlex
- W124314106
- Cited by
- 215
- References
- 195
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 19 · 2023: 19 · 2022: 17 · 2021: 15 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 11 · 2016: 10 · 2015: 12 · 2014: 16 · 2013: 12 · 2012: 12
- FWCI
- 32.78
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM082946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- adeno-associated virus, capsid structure, capsid assembly, DNA packaging, cell tropism, receptor recognition, capsid uncoating, antibody neutralization, serotypes, gene delivery vectors, host cell interactions
- MeSH terms
- Dependovirus, Antibody Formation, Capsid, Humans, Models, Molecular, Endosomes, Viral Proteins, Protein Structure, Secondary
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