The DOI matches its Crossref record; 134 of the 135 references it cites were found in a registry or an index.
Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids
Open accessAbstract
More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity. Furthermore, directed evolution of shuffled genome libraries can identify engineered variants with unique properties, and rational modification of the viral capsid can alter tropism, reduce blockage by neutralizing antibodies, or enhance transduction efficiency. This large number of AAV variants and engineered capsids provides a varied toolkit for gene delivery to the CNS and retina, with specialized vectors available for many applications, but selecting a capsid variant from the array of available vectors can be difficult. This chapter describes the unique properties of a range of AAV variants and engineered capsids, and provides a guide for selecting the appropriate vector for specific applications in the CNS and retina.
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“With translational studies in mind, it is important to demonstrate consistent tropism of a particular rAAV, as examples where the tropism of a given rAAV capsid does not remain consistent in rodents and higher animals have been described [7].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“we performed co-labeling via IHC and confirmed the results of previous studies (Castle et al., 2016; Hudry et al., 2016; Schuster et al., 2014; Aschauer et al., 2013; Hinderer et al., 2014; Samaranch et al., 2012), showing that AAV9, when injected directly into the adult brain parenchyma, is not expressed in microglia and minimally expressed in astrocytes (Figure S5).”
From The neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer's disease (2022) · cites this paper as Castle et al., 2016
Experimental — accuracy not yet measuredIn the citing paper
“RPE cells can be targeted using AAV1, AAV4, or AAV6 vectors or with the engineered AAV2-7m8 vector, and photoreceptors and Müller glial cells are targeted by serotypes AAV2, AAV5, AAV6, AAV7, AAV8, and AAV9 as well as engineered AAV2-7m8 and AAV8BP2 vectors.56,112–116”
From Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions (2023) · cites this paper as [112]
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Citations
Cites
Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2009) · Nature Biotechnology · doi:10.1038/nbt.1515 · Cited by 1,456
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“For many AAV serotypes cellular surface receptors or binding determinants have been identified, including sialic acid for AAVs 1, 4, 5, and 6 [7, 8], heparan sulfate proteoglycan (HSPG) for AAV2 [9], the laminin receptor for AAV8 [10], and galactose for AAV9 [11, 12].”
BackgroundClades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues
Gao, G., Vandenberghe, L. H., Alvira, M. R., Lu, Y., Calcedo, R., Zhou, X., & Wilson, J. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6381-6388.2004 · Cited by 1,070 · cited 1×
“However, a large number of alternative capsid variants have been identified from humans, baboons, chimpanzees, and rhesus, pigtailed, and cynomolgus macaques [5, 6].”
BackgroundSelf-citationBurger, C., Gorbatyuk, O. S., Velardo, M. J., Peden, C. S., Williams, P., Zolotukhin, S., Reier, P. J., Mandel, R. J., & Muzyczka, N. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.05.024 · Cited by 741 · cited 2×
“AAV2 diffuses less readily through both the brain and spinal cord parenchyma when compared against other serotypes, and therefore mediates transduction over a smaller area [19, 28, 32, 33].”
BackgroundDalkara, D., Byrne, L. C., Klimczak, R. R., Visel, M., Yin, L., Merigan, W. H., Flannery, J. G., & Schaffer, D. V. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005708 · Cited by 734
αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
Summerford, C., Bartlett, J. S., & Samulski, R. J. (1999) · Nature Medicine · doi:10.1038/4768 · Cited by 711
Zhong, L., Li, B., Mah, C. S., Govindasamy, L., Agbandje-McKenna, M., Cooper, M., Herzog, R. W., Zolotukhin, I., Warrington, K. H., Weigel-Van Aken, K. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802866105 · Cited by 558
Directed evolution of adeno-associated virus yields enhanced gene delivery vectors
Maheshri, N., Koerber, J. T., Kaspar, B. K., & Schaffer, D. V. (2006) · Nature Biotechnology · doi:10.1038/nbt1182 · Cited by 538 · cited 1×
“In addition to peptide insertion, the development of capsid shuffling [93] and directed evolution [94], discussed in Chapter 11, has generated many promising novel AAV variants.”
BackgroundDavidson, B. L., Stein, C. S., Heth, J. A., Martins, I., Kotin, R. M., Derksen, T. A., Zabner, J., Ghodsi, A., & Chiorini, J. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3428 · Cited by 531 · cited 5×
“AAVs 1, 2, 4, 5, 6, and 8 do not appear to extensively penetrate the brain parenchyma when administered to the CSF [ 22 , 39 , 40 ].”
InfluentialGray, S. J., Matagne, V., Bachaboina, L., Yadav, S., Ojeda, S. R., & Samulski, R. J. (2011) · Molecular Therapy · doi:10.1038/mt.2011.72 · Cited by 501
Cited by
Sorted by citations
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
“For example, the CMV promoter has been shown to be silenced in the central nervous system (CNS) [16].”
BackgroundInfluentialTherapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality
Hudry, E., & Vandenberghe, L. H. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.017 · Cited by 384
Self-citationAdeno-Associated Virus-Based Gene Therapy for CNS Diseases
Hocquemiller, M., Giersch, L., Audrain, M., Parker, S., & Cartier, N. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.087 · Cited by 291
Viral vectors for therapy of neurologic diseases
Choudhury, S. R., Hudry, E., Maguire, C. A., Sena-Esteves, M., Breakefield, X. O., & Grandi, P. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.02.013 · Cited by 190
“Recent efforts at capsid reengineering (Castle et al., 2016) have led to the generation of two AAV capsid variants, AAV-AS (Choudhury et al.”
BackgroundA Student’s Guide to Neural Circuit Tracing
Saleeba, C., Dempsey, B., Le, S., Goodchild, A., & McMullan, S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00897 · Cited by 153
Metadata
- Authors
- Castle, M. J., Turunen, H. T., Vandenberghe, L. H., & Wolfe, J. H.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Wolfe, John H.
- Venue
- Methods in Molecular Biology
- Publisher
- Springer New York
- Published
- 2016
- Volume
- 1382
- Pages
- 133-149
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- PMC
- PMC4993104
- OpenAlex
- W2176154815
- Cited by
- 151
- References
- 135
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 22 · 2023: 15 · 2022: 10 · 2021: 24 · 2020: 14 · 2019: 17 · 2018: 8 · 2017: 11 · 2016: 5
- FWCI
- 23.28
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1dp1od008267-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK063973)
- National Institute of Neurological Disorders and Stroke (R01NS038690, T32NS007413)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD079066)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- adeno-associated virus, AAV capsid engineering, viral tropism, retinal gene delivery, receptor binding, peptide insertion, directed evolution, neutralizing antibodies, transduction efficiency, vector selection
- MeSH terms
- Dependovirus, Animals, Capsid, Central Nervous System, Genetic Vectors, Humans, Organ Specificity, Retina, Gene Transfer Techniques, Viral Tropism
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