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]
Citations
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Cited by
Sorted by citations
Items 201–217 of 217
Protein Carrier AAVPreprint
Hoffmann, M. D., Sorensen, R. J., Extross, A., He, Y., & Schmidt, D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.14.607995
“Since its discovery as a contamination of Adenovirus productions in 1965 1,2 , studies of Adeno-associated virus (AAV) have spread the gamut from understanding its basic biology (reviewed in 3,4 ) to engineering AAV vectors for therapeutic applications (reviewed in 5 ).”
BackgroundAdeno-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
Kopec, B. M., Ebert, E., Ulapane, K. R., Moral, M. E. G., & Siahaan, T. J. (2025) · Neuromethods · doi:10.1007/978-1-0716-4474-4_12
Uhl, L. K., & Fasina, O. O. (2025) · PubMed Central · doi:10.3390/v17070984 · Cited by 1
“However, over the years, about nine serotypes of AAV, namely AAV1-AAV9, have been reported in the literature [27].”
Cui, J., Wang, W., Liu, D., Han, D., Jin, X., & Wei, W. (2025) · Human Gene Therapy · doi:10.1177/10430342251393707
Singh, I., Kumar, A., Chaudhary, A. K., Dalal, J. S., Sharma, A., Sharma, J., Ratn, A., Dhakad, M. S., & Sharma, D. (2026) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/14703203261437332
Characterization of rAAV vectors packaging in baculovirusinfected insect cells
Penaud‐Budloo, M. (2018) · theses.fr (ABES) · doi:10.70675/c5cff6daz8fe4z430cz80e6z97a11cc59c8e
Nan, X., Sun, J., Jiao, Y., Li, W., Chen, Y., Liu, Y., Xu, B., Yu, L., Guo, W., & Wu, Y. (2026) · Human Gene Therapy · doi:10.1177/10430342261432669
“44 By identifying key regions involved in receptor binding, researchers can introduce site-directed mutations or insert speci fi c amino acid sequences to alter capsid surface properties and enhance receptor af fi nity in hard-to-transduce tissues 45 (Fig.”
Preclinical gene therapy using recombinant AAV vectors in mouse models of two human diseases
Günes, Y. Ö. (2022) · theses.fr (ABES) · doi:10.70675/52c9a808z1652z42c4zae82zc812b95f1723
Etude des réponses T CD8+ après transfert de gène par rAAV ciblant le muscle
Jeanpierre, L. (2024) · theses.fr (ABES) · doi:10.70675/430aceacz50d2z426bz907dz876c55d1e935
Computational Rational Design of Larger AAV Icosahedral CapsidsPreprint
Cioffi, M., & Luque, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.09.724008
Environmental and developmental factors shape anti-AAV immunity in pigs
Iroanya, G. I., Raju, I., Boosani, C. S., Subramanyam, P. N., Byrne, A. K., Wells, K. D., & Green, J. A. (2026) · Gene Therapy · doi:10.1038/s41434-026-00625-1
The Sources of Biological Variation: Natural Viral-Cellular Engineering in Cognition-Based Evolution
Miller, W. B., Baluška, F., Slijepčević, P., & Reber, A. S. (2026) · Springer eBooks · doi:10.1007/978-3-032-23779-8_9
Nanobody-Functionalized AAV achieves Promoter-independent Neuronal Targeting in the CNS åPreprint
Extross, A., de Velasco, E. M. F., He, Y., Wickman, K., & Schmidt, D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.18.752817
“Specifically, the T456 residue located within VR4 of the AAV-DJ capsid serves as a structural benchmark for targeted insertions, making it a position for the engineering approaches detailed here 29, 33, 39, 40 .”
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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