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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.
In the citing paper
“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
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“However, this can be advantageous when the goal is to transduce a small number of neurons with minimal spread in a specific brain region.(41) As indicated above, currently 11 natural AAV serotypes have been identified, all with different natural tropisms and transduction properties.”
BackgroundO’Carroll, S. J., Cook, W. H., & Young, D. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.618020 · Cited by 112
Emerging Gene Therapies for Genetic Hearing Loss
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Toward an elucidation of the molecular genetics of inherited retinal degenerations
Farrar, G. J., Carrigan, M., Dockery, A., Millington‐Ward, S., Palfi, A., Chadderton, N., Humphries, M. M., Kiang, A. S., Kenna, P. F., & Humphries, P. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx185 · Cited by 97
“Strategies such as directed evolution are also expediting the generation of AAV serotypes with a predilection for specific retinal cell types (59,60).”
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“AAV2-Retro effectively transduces reticulospinal, rubrospinal, and corticospinal neurons AAV serotypes vary widely in their tropism for different types of neurons and their onset of transgene expression (Castle et al., 2016).”
BackgroundVirus-Derived Peptides for Clinical Applications
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Vectors and Gene Delivery to the Retina
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“AAV serotypes 1, 4, and 6 seem to have a preference for RPE cells rather than their underlying photoreceptors and should be used when exclusive RPE transduction is preferred (Castle et al. 2016).”
BackgroundIs Viral Vector Gene Delivery More Effective Using Biomaterials?
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“While AAV2 undergoes anterograde transport and AAV6 undergoes retrograde transport [40], studies have demonstrated that AAV serotypes 1, 5, 8, and 9 undergo both anterograde and retrograde transport [46,56,59].”
BackgroundCRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease
Rahman, M. U., Bilal, M., Shah, J. A., Kaushik, A. K., Teissèdre, P., & Kujawska, M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061252 · Cited by 65
Adeno-Associated Virus Vector for Central Nervous System Gene Therapy
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Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease
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MethodViral Tools for Neural Circuit Tracing
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“Different AAV serotypes exhibit different tropisms and can transduce neural cells in vivo and in vitro [28, 29].”
BackgroundNon-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases
Abdelmonem, B. H., Kamal, L. T., Wardy, L. W., Ragheb, M., Hanna, M. M., Elsharkawy, M., & Abdelnaser, A. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1534862 · Cited by 55
“For example, adenovirus naturally targets cells in the nervous system, while retrovirus typically infect dividing cells, and lentivirus target a wider range of cells, including immune cells or stem cells (283, 284).”
Update on viral gene therapy clinical trials for retinal diseases
Cheng, S.-Y., & Punzo, C. (2022) · Human Gene Therapy · doi:10.1089/hum.2022.159 · Cited by 49
“To date, there are more than 100 AAV serotypes, many of which infect neurons.(42)”
BackgroundIntravenous Infusion of AAV for Widespread Gene Delivery to the Nervous System
Gessler, D. J., Tai, P. W. L., Li, J., & Gao, G. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9139-6_8 · Cited by 51
Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease
Finkel, Z., Esteban, F., Rodriguez, B., Fu, T., Ai, X., & Cai, L. (2021) · Cells · doi:10.3390/cells10082045 · Cited by 50
“, neurons, astrocytes, NSPCs, and oligodendrocytes [85,86].”
Optimized Adeno-Associated Virus Vectors for Efficient Transduction of Human Retinal Organoids
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“Previously reported work evaluated rAAV transduction in retinal organoids of various maturation stages, for example, at day (D) 42, 28 D140, 16,29 or > D200 18,23 in culture.”
Synthetic immunomodulation with a CRISPR super-repressor in vivo
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Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors
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Qureshi, Y. H., Berman, D. E., Marsh, S. E., Klein, R. L., Patel, V. M., Simoes, S., Kannan, S., Petsko, G. A., Stevens, B., & Small, S. A. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110262 · Cited by 31
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“Since the diffusion of AAV2 is limited and it is highly selective for neurons [26], recombinant AAV (rAAV) vectors currently in use are based on the framework of AAV2.”
BackgroundPan, X., Sands, S. A., Yue, Y., Zhang, K., LeVine, S. M., & Duan, D. (2019) · Human Gene Therapy · doi:10.1089/hum.2019.008 · Cited by 29
“Besides peripheral contribution, therapeutic galactosylceramidase can also be produced in the CNS in situ following systemic AAV9 injection because AAV9 can cross the BBB.53,56 Indeed, we observed increased galactosylceramidase activity in the brain of AAV-injected mice by enzymatic staining (Fig.”
BackgroundInfluentialDNA‐editing enzymes as potential treatments for heteroplasmic mtDNA diseases
Zekonyte, U., Bacman, S. R., & Moraes, C. T. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13055 · Cited by 29
Yoon, S. Y., Hunter, J. E., Chawla, S., Clarke, D. L., Molony, C. M., O’Donnell, P. A., Bagel, J. H., Kumar, M., Poptani, H., Vite, C. H., et al. (2020) · Brain · doi:10.1093/brain/awaa161 · Cited by 27
“However, in the brain, the diseased cells require widespread gene delivery to correct the globally distributed lesions (Castle et al., 2016).”
BackgroundSelf-citationIn vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system
Allen, J. K., Sutherland, T. C., Prater, A. R., Geoffroy, C. G., & Pellois, J. (2022) · Science Advances · doi:10.1126/sciadv.abo2954 · Cited by 30
Zhou, L., Wang, Y., Xu, Y., Zhang, Y., & Zhu, C. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03232-2 · Cited by 26
“…such as gene editing and gene delivery systems may offer novel approaches to correct aberrant microglial function and restore CNS homeostasis in various neurodegenerative disorders. the majority of current AAV serotypes or variants exhibit tropism primarily towards neurons or astrocytes [32].”
BackgroundCardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy
Riching, A. S., & Song, K. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.637538 · Cited by 29
“On the other hand, delivery of AAVs that display tropism for the heart including AAV6 and AAV9 are also well-established to infect other organs including the brain, lung, liver, and skeletal muscle (Wu et al., 2006; Castle et al., 2016; Naso et al., 2017).”
BackgroundHutt, J. A., Assaf, B. T., Bolon, B. N., Cavagnaro, J. A., Galbreath, E. J., Grubor, B., Kattenhorn, L. M., Romeike, A., & Whiteley, L. O. (2021) · Toxicologic Pathology · doi:10.1177/01926233211041962 · Cited by 27
Calcium imaging for analgesic drug discovery
Iseppon, F., Linley, J. E., & Wood, J. N. (2022) · Neurobiology of Pain · doi:10.1016/j.ynpai.2021.100083 · Cited by 25
“…is strongly dependent on the composition of the capsid proteins encapsulating the DNA, with small differences separating the various serotypes which differ in their optimal tropism towards different tissues and cell types both in vitro and in vivo (Castle et al., 2016; Haggerty et al., 2020).”
Weber‐Adrian, D., Kofoed, R. H., Silburt, J., Noroozian, Z., Shah, K., Burgess, A., Rideout, S., Kügler, S., Hynynen, K., & Aubert, I. (2021) · Scientific Reports · doi:10.1038/s41598-021-81046-5 · Cited by 27
Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann–Pick disease type C1 mice
Davidson, C. D., Gibson, A. L., Gu, T., Baxter, L. L., Deverman, B. E., Beadle, K., Incao, A. A., Rodriguez‐Gil, J. L., Fujiwara, H., Jiang, X., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202101040 · Cited by 25
“Advances in the identification of novel serotypes that cross the BBB in humans, and capsid engineering to derive CNS trophic variants (Castle et al, 2016; Hudry et al, 2018; Sullivan et al, 2018; Hanlon et al, 2019; Havlik et al, 2020) should help improve vectors, as recent studies highlight (Gray…”
ResultEmerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders
Limia, C. E. G., Baird, M., Schwartz, M., Saxena, S., Meyer, K., & Wein, N. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12121979 · Cited by 28
Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology
Sizemore, R. J., Seeger-Armbruster, S., Hughes, S. M., & Parr‐Brownlie, L. C. (2016) · Journal of Neurophysiology · doi:10.1152/jn.01131.2015 · Cited by 24
“The change to other serotypes has had a significant impact on both tropism and targeting of neurons via anterograde and retrograde transport (reviewed in Castle et al. 2016).”
BackgroundInfluentialAnti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma
Hicks, M. J., Chiuchiolo, M. J., Ballon, D., Dyke, J. P., Aronowitz, E., Funato, K., Tabar, V. S., Havlicek, D. F., Fan, F., Sondhi, D., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162978 · Cited by 23
Concepts and Strategies in Retinal Gene Therapy
Aguirre, G. D. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22978 · Cited by 24
“However, the vector serotype toolbox is large, and new versions are continually being developed.(60,61) Among the new vectors being developed for dog studies are those identified by directed evolution using the canine retina.”
Are Viral Vectors Any Good for RNAi Antiviral Therapy?
Lundstrom, K. H. (2020) · Viruses · doi:10.3390/v12101189 · Cited by 21
“In contrast, AAV has emerged as a good candidate, especially the hepatotropic AAV8 serotype [23].”
BackgroundEngineering novel adeno-associated viruses (AAVs) for improved delivery in the nervous system
Carneiro, A. D., & Schaffer, D. V. (2024) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2024.102532 · Cited by 22
Skukan, L., Brezak, M., Ister, R., Klimaschewski, L. P., Vojta, A., Zoldoš, V., & Gajović, S. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211039997 · Cited by 20
“LV vectors can be pseudotyped with a variety of different cell affinity glycoprotein envelopes, while peptides inserted in AAVs capsid can determine cell tropism.(13,14) An important advantage of AAVs and LVs lies in their capability of stable gene expression as they enter the nucleus of infected cells through a nucle…”
BackgroundUnderstanding the Potential of Genome Editing in Parkinson’s Disease
Arango, D., Bittar, A., Esmeral, N. P., Ocasión, C., Muñoz-Camargo, C., Cruz, J. C., Reyes, L. H., & Bloch, N. I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179241 · Cited by 24
“Capsid engineering is a suitable route to accomplish specific requirements of a particular gene-editing application and can efficiently target the nervous system and crossing the BBB due to the tropism inherent to viruses [191].”
BackgroundPRPF31-retinitis pigmentosa: Challenges and opportunities for clinical translation
Aweidah, H., Xi, Z., Sahel, J., & Byrne, L. C. (2023) · Vision Research · doi:10.1016/j.visres.2023.108315 · Cited by 19
“Currently, most clinical trials for retinal gene therapy employ adenoassociated viruses as the gene delivery vehicle, as they have been shown to be safe, with relatively low immunogenicity compared to other viruses and tropism for retinal neurons and RPE (Castle et al., 2016; Dalkara et al., 2013).”
Targeting Progranulin as an Immuno-Neurology Therapeutic Approach
Boylan, M. A., Pincetic, A., Romano, G. J., Tatton, N. A., Kenkare-Mitra, S., & Rosenthal, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115946 · Cited by 19
“An additional consideration is ensuring adequate viral spread from the injection site; transduction varies according to AAV serotype, with AAV1 and AAV9 associated with neural and glial transduction when administered via intraparenchymal injection [192].”
BackgroundInfluentialViral Vectors, Engineered Cells and the CRISPR Revolution
DiCarlo, J. E., Deeconda, A., & Tsang, S. H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-63904-8_1 · Cited by 19
A Matter of Genes: The Hurdles of Gene Therapy for Epilepsy
Ingusci, S., Cattaneo, S., Verlengia, G., Zucchini, S., & Simonato, M. (2019) · Epiliepsy currents/Epilepsy currents · doi:10.1177/1535759718822846 · Cited by 19
In vivo identification of astrocyte and neuron subproteomes by proximity-dependent biotinylation
Soto, J. S., Jami‐Alahmadi, Y., Wohlschlegel, J. A., & Khakh, B. S. (2023) · Nature Protocols · doi:10.1038/s41596-023-00923-7 · Cited by 17
Advancements in Viral Gene Therapy for Gaucher Disease
Kulkarni, A., Chen, T., Sidransky, E., & Han, T. (2024) · Genes · doi:10.3390/genes15030364 · Cited by 16
“The AAV2 serotype has been widely evaluated in gene therapy, and most recombinant AAVs contain the AAV2 ITR sequence [93].”
BackgroundSun, J., Hua, B., Chen, X., Samulski, R. J., & Li, C. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.016 · Cited by 16
Roig-Soriano, J., Edo, Á., Verdés, S., Martín-Alonso, C., Sánchez‐de‐Diego, C., Rodríguez-Estévez, L., Serrano, A. L., Abraham, C. R., Bosch, A., Ventura, F., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.02.030 · Cited by 16
Therapeutic Application and Structural Features of Adeno-Associated Virus Vector
Matsuzaka, Y., & Yashiro, R. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46080499 · Cited by 15
“…types of cells, differs among serotypes, it is possible to design vectors that deliver therapeutic genes to specific tissues by selecting an appropriate capsid sequence [97]. rAAV vectors are mainly produced by HEK293 (human embryonic kidney) cells or Sf9 (spodoptera frugiperda) cells [98–100].”
BackgroundViral and nonviral nanocarriers for in vivo CRISPR-based gene editing
Guo, Z., Zhu, A. T., Fang, R. H., & Zhang, L. (2024) · Nano Research · doi:10.1007/s12274-024-6748-5 · Cited by 18
Day, J., Mendell, J. R., Burghes, A. H. M., van Olden, R. W., Adhikary, R. R., & Dilly, K. W. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.101117 · Cited by 14
Exploring microglial replacement: From disease models to clinical translation
Zhou, K., Wang, Y., Xu, Y., Zhang, Y., & Zhu, C. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.06.011 · Cited by 13
“Similar strategies could also be applied to microglial depletion in the brain; however, the specificity of these nanoparticle formulations for microglia remains largely unknown.”
Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons
Bragg-Gonzalo, L., Aguilera, A. A., González-Arias, C., de León-Reyes, N. S., Sánchez-Cruz, A., Carballeira, P., Leroy, F., Perea, G., & Nieto, M. (2024) · Science Advances · doi:10.1126/sciadv.adj9911 · Cited by 15
“AAV serotype 8 was chosen because it shows strong neuronal tropism and high transgene expression in the brain ( 65 , 66 ).”
BackgroundTis21-gene therapy inhibits medulloblastoma growth in a murine allograft model
Presutti, D., Ceccarelli, M., Micheli, L., Papoff, G., Santini, S., Samperna, S., Lalli, C., Zentilin, L., Ruberti, G., & Tirone, F. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194206 · Cited by 13
Krabbe Disease: Prospects of Finding a Cure Using AAV Gene Therapy
Nasir, G., Chopra, R., Elwood, F., & Ahmed, S. S. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.760236 · Cited by 13
“If the beneficial effects of BMT are actually associated more with removal of GALC-lacking myeloid progenitor cells than the infusion of GALC-positive cells, it may be worthwhile to target the hematopoietic stem cell population directly by combining two different AAV serotypes, delivered by two separate routes, such a…”
BackgroundInfluentialEmerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies
von Jonquières, G., Rae, C. D., & Housley, G. D. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.661857 · Cited by 12
Gene therapy for Leber hereditary optic neuropathy
Battista, M., Carelli, V., Bottazzi, L., Bandello, F. M., Cascavilla, M. L., & Barboni, P. (2024) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2024.2359015 · Cited by 10
“In particular, this aim could be reached following different modalities: chemical modification of the capsid, creating mosaic capsids (mixing subunits from two or more different serotypes), peptide insertion, capsid shuffling, rational design or inclusion of mRNA [40].”
BackgroundLu, W.-H., Chang, T.-T., Chang, Y., Liu, Y.-H., Lin, C.-H., Suen, C., Hwang, M., & Huang, Y. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01061-2 · Cited by 11
“However, several studies have indicated that AAV8 has higher glial tropism than AAV9 [73–76], so we conducted additional experiments (Additional File 1: Fig.”
BackgroundMethodOptogenetics – New Potentials for Electrophysiology
Кулешова, Е. П. (2019) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-019-00711-5 · Cited by 9
Viral Vector Delivery of DREADDs for CNS Therapy
Pickering, C. A., & Mazarakis, N. D. (2021) · Current Gene Therapy · doi:10.2174/1566523221666210211102435 · Cited by 11
Cell-Based Therapies: Strategies for RegenerationPreprint
Pavlou, M., & Reh, T. A. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041306 · Cited by 10
Rationally engineered novel AAV capsids for intra-articular gene delivery
Li, W., Feng, S. L., Herrschaft, L., Samulski, R. J., & Li, C. (2024) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2024.101211 · Cited by 12
Enbar, T., Hickmott, J. W., Siu, R., Gao, D., Flores, E. G., Smart, J., Casabuenas, D. L., Faiz, M., & Morshead, C. M. (2024) · Scientific Reports · doi:10.1038/s41598-024-79124-5 · Cited by 9
Fluorescence imaging of peripheral nerve function and structure
Yang, X., Zhang, Y., Liu, Y., Wang, Y., & Zhou, N. (2023) · Journal of Materials Chemistry B · doi:10.1039/d3tb01927f · Cited by 9
Acoustically Targeted Chemogenetics for Noninvasive Control of Neural CircuitsPreprint
Szablowski, J. O., Lue, B., Lee‐Gosselin, A., Malounda, D., & Shapiro, M. G. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/241406 · Cited by 9
Basic Concepts in Viral Vector-Mediated Gene Therapy
Benskey, M. J., Sandoval, I. M., Miller, K., Sellnow, R. C., Gezer, A. O., Kuhn, N. C., Vashon, R., & Manfredsson, F. P. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9065-8_1 · Cited by 9
Luchicchi, A., Pattij, T., Viaña, J. N. M., de Kloet, S. F., & Marchant, N. J. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.109004 · Cited by 8
Stevens, L., Larsen, L. E., Lysebettens, W. V., Carrette, E., Boon, P., Raedt, R., & Vonck, K. E. J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.663337 · Cited by 8
Sharma, S., Joshi, V., & Kumar, V. (2025) · Clinical and Translational Neuroscience · doi:10.3390/ctn9030032 · Cited by 7
“AAV9 is particularly well-suited for targeting neurodegenerative tissues due to its strong tissue-tropism and proven ability to cross the blood-brain barriers, as demonstrated in several preclinical animals’ studies [51].”
Amato, A., Wongchaisuwat, N., Lamborn, A., Schmidt, R., Everett, L. A., Yang, P. G., & Pennesi, M. E. (2023) · Saudi Journal of Ophthalmology · doi:10.4103/sjopt.sjopt_175_23 · Cited by 7
“[51] Moreover, while bestrophinopathies are progressive, the rate of decline is typically slow and allows a wider therapeutic window, as central PRs remain viable for decades and many patients maintain an excellent VA until their fifth decade of life.”
BackgroundHayashi, Y., Sehara, Y., Watano, R., Ohba, K., Takayanagi, Y., Sakiyama, Y., Muramatsu, K., & Mizukami, H. (2024) · Human Gene Therapy · doi:10.1089/hum.2023.106 · Cited by 7
“21,22 AAVrh8, 9, and rh10 have been reported to transduce genes throughout the central nervous system when administered intravenously.”
Narcisse, D., Mustafi, S. M., Carlson, M. E., Batabyal, S., Kim, S. H., Wright, W. W., & Mohanty, S. K. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.750663 · Cited by 7
Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls
Berkowitz, S. T., & Finn, A. P. (2024) · Current Opinion in Ophthalmology · doi:10.1097/icu.0000000000001043 · Cited by 8
A Quantitative Chloride Channel Conductance Assay for Efficacy Testing of AAV.BEST1
Wood, S., McClements, M. E., de la Cámara, C. M.-F., Patrício, M. I., Uggenti, C., Sekaran, S., Barnard, A. R., Manson, F. D. C., & MacLaren, R. E. (2019) · Human Gene Therapy Methods · doi:10.1089/hgtb.2018.267 · Cited by 7
“Additionally, numerous AAV serotypes exhibit good tropism for RPE cells (AAV1, 2, 4, 5, 7, 8, and 9), 30 in particular AAV2 and AAV4, which have been used successfully to transduce the RPE in clinical trials.”
Bazick, H., James, L. M., Taylor‐Blake, B., Wolter, J. M., & Zylka, M. J. (2025) · Gene Therapy · doi:10.1038/s41434-025-00582-1 · Cited by 7
PHP.B/eB Vectors Bring New Successes to Gene Therapy for Brain Diseases
Reynaud-Dulaurier, R., & Decressac, M. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.582979 · Cited by 6
Prospective approaches to gene therapy computational modeling – spotlight on viral gene therapy
Choules, M. P., Bonate, P. L., Heo, N., & Weddell, J. C. (2023) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-023-09889-1 · Cited by 7
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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