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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Examples where the tropism of a given rAAV capsid does not remain consistent in rodents and higher animals have been described.
“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]
Section 2 (page unavailable) reports that AAV8 tropism differed between vector preparations, even under identical injection conditions. That supports the broader point that a given serotype’s tropism can vary, but the passage does not describe a difference between rodents and higher animals; the chapter’s nonhuman-primate examples do not establish that comparison. (LLM, conf=0.82)
Experimental — accuracy not yet measuredRPE cells can be targeted using AAV1, AAV4, AAV6, or the engineered AAV2-7m8 vector; photoreceptors and Müller glial cells are targeted by serotypes AAV2, AAV5, AAV6, AAV7, AAV8, AAV9, AAV2-7m8, and AAV8BP2.
“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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“In primary cultures of rat nervous cells, AAV5 appears to possess a strong glial tropism, and gene expression rarely colocalizes with the neuronal marker Methods Mol Biol.”
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Targeting photoreceptors via intravitreal delivery using novel, capsid-mutated AAV vectors
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“Indeed, mutating several surface exposed tyrosine and threonine residues signifi cantly increased the transduction effi ciency of AAVs 2, 5, and 8 [ 111 , 112 ].”
BackgroundMolecular signatures of disease brain endothelia provide new sites for CNS-directed enzyme therapy
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“To date, improved targeting of skeletal muscle [81, 82], cardiac muscle [83], vasculature [84– 86], lung [87, 88], diseased brain endothelial cells [89], retina [90], ovarian cancer cells [91] and breast cancer cells [88] has been reported.”
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“In nonhuman primate subretinal injections, AAV8 efficiently targets rod PRs [54], while AAV9 is superior for cone PRs and retains tropism for rod PRs [53].”
BackgroundInfluentialGeneration and characterization of chimeric recombinant AAV vectors
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“Hybrid capsids of AAV1 and AAV2 (AAV1/2) can mediate stronger transgene expression in lung and muscle in vivo than either of the parental serotypes alone [69].”
BackgroundMolecular Engineering of Viral Gene Delivery Vehicles
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Comparison of Adeno-Associated Viral Vector Serotypes for Spinal Cord and Motor Neuron Gene Delivery
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“Thus, CSF injection of AAV4 can mediate transduction of epithelial cells, CSF injection of AAV7 or 9 can mediate widespread transduction of cortical, cerebellar, and spinal neurons, CSF injection of AAV6 can mediate transduction of spinal motor neurons, and CSF injection of AAV8 can mediate transduction of large-diame…”
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“Within the brain, AAV9 is most frequently observed to undergo axonal transport, and is the recommended choice if distal transduction is desired [21, 23, 34, 36, 57, 60].”
BackgroundSelf-citationSamaranch, L., Salegio, E. A., Sebastián, W. S., Kells, A. P., Bringas, J. R., Forsayeth, J., & Bankiewicz, K. S. (2013) · Human Gene Therapy · doi:10.1089/hum.2013.005 · Cited by 155 · cited 1× · see citing works
“In contrast, AAV7 and AAV9 can bypass the ependymal layer following intrathecal injection, penetrating the parenchyma and transducing neurons throughout the cortex, cerebellum, and spinal cord [37, 38].”
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“Further, AAV1/2 appears to combine the tropism of AAV2 for TH-positive dopamine neurons with the ability of AAV1 to diffuse more widely through brain tissue, mediating strong transduction of dopamine neurons in the substantia nigra, and has been used to model Parkinson’s disease in the rat [70].”
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“AAV serotypes 1, 2, 6, 7, 8, and 9 transduce both neurons and astrocytes in primary culture [16, 17].”
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Erratum: Genetic capsid modifications allow efficient re-targeting of adeno-associated virus type 2
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Glial promoter selectivity following AAV-delivery to the immature brain
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“ip1 cells more than 100-fold [ 64 ].”
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“The earliest successful alterations of AAV tropism by capsid engineering relied on insertion of short peptides into the AAV capsid [72].”
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“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].”
BackgroundVascular bed-targeted in vivo gene delivery using tropism-modified adeno-associated viruses
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Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1
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“AAV1 appears to be more effective than AAVs 2, 3, 4, 5, or 6 for retrograde transduction of motor neurons following muscle or sciatic nerve injection [56].”
BackgroundAsuri, P., Bartel, M. A., Vazin, T., Jang, J.-H., Wong, T. B., & Schaffer, D. V. (2012) · Molecular Therapy · doi:10.1038/mt.2011.255 · Cited by 119 · cited 1× · see citing works
“Capsids with improved transduction of heart [ 95 ], lung [ 96 , 97 ], Müller glia in the retina [ 98 ], CNS [ 99 – 101 ], and neural and pluripotent stem cells [ 102 , 103 ] have been described, with numerous others yet unpublished.”
BackgroundBoye, S. E., Alexander, J. J., Boye, S. L., Witherspoon, C. D., Sandefer, K. J., Conlon, T. J., Erger, K., Sun, J., Ryals, R., Chiodo, V. A., et al. (2012) · Human Gene Therapy · doi:10.1089/hum.2012.125 · Cited by 117 · cited 1× · see citing works
“shown to target both rod and cone PRs, but has not been compared directly in this setting against other serotypes [55].”
ResultBuilding a Better Vector: The Manipulation of AAV Virions
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“Hybrid capsids are designed to harness the structural similarity among AAVs, combining beneficial properties from two or more different serotypes by co-expressing their capsid proteins during vector production [68].”
BackgroundAdeno-associated virus vector-mediated transduction in the cat brain
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AAV9 targets cone photoreceptors in the nonhuman primate retina
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“In nonhuman primate subretinal injections, AAV8 efficiently targets rod PRs [54], while AAV9 is superior for cone PRs and retains tropism for rod PRs [53].”
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“Capsids with improved transduction of heart [95], lung [96, 97], Müller glia in the retina [98], CNS [99–101], and neural and pluripotent stem cells [102, 103] have been described, with numerous others yet unpublished.”
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“Axonal transport is a fundamental property of AAV vectors, and thus any vector that is endocytosed at high levels by projection neurons is likely to transduce distal brain regions [57, 58].”
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A muscle-targeting peptide displayed on AAV2 improves muscle tropism on systemic delivery
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“To date, improved targeting of skeletal muscle [81, 82], cardiac muscle [83], vasculature [84– 86], lung [87, 88], diseased brain endothelial cells [89], retina [90], ovarian cancer cells [91] and breast cancer cells [88] has been reported.”
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“WPREs have also been implicated as a contributing or causal factor in oncogenesis in preclinical studies, likely via an ORF within the WPRE [ 127 ].”
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“AAV4 possesses strong glial tropism in vivo, and primarily drives gene expression within glial fibrillary acidic protein (GFAP)-positive astrocytes [25].”
BackgroundUtility of PEGylated recombinant adeno-associated viruses for gene transfer
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“Indeed, moderate success has been achieved by coating capsids with poly(ethylene) glycol [65], poly-[N-(2-hydroxypropyl) methacrylamide] [66], and α-dicarbonyl compounds [67].”
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“AAV9, however, has relatively weak neuronal tropism in vitro, with less than 50 % of transduced cells representing neurons [17].”
BackgroundSelf-citationAltering AAV tropism with mosaic viral capsids
Gigout, L. I., Rebollo, P., Clement, N., Warrington, K. H., Muzyczka, N., Linden, R. M., & Weber, T. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.03.005 · Cited by 79 · cited 1× · see citing works
“This is an important consideration, as the density of receptor-binding peptides on a capsid can affect its tropism [79].”
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“To date, improved targeting of skeletal muscle [81, 82], cardiac muscle [83], vasculature [84– 86], lung [87, 88], diseased brain endothelial cells [89], retina [90], ovarian cancer cells [91] and breast cancer cells [88] has been reported.”
BackgroundStieger, K., Colle, M.-A., Dubreil, L., Mendes-Madeira, A., Weber, M., Meur, G. L., Deschamps, J. Y., Provost, N., Nivard, D., Chérel, Y., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.41 · Cited by 75 · cited 1× · see citing works
“AAV8 also possesses tropism for ganglion cells and cells of the inner nuclear layer [50, 54], and demonstrates greater tropism for PRs than AAV2 [54].”
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“However, others have observed astroglial transduction with AAVs 1, 2, 5, 6, and 8 [22–24], and AAV8 has also been observed to transduce oligodendrocytes within the cortex [24].”
BackgroundVandenberghe, L. H., Breous, E., Nam, H.-J., Gao, G., Xiao, R., Sandhu, A., Johnston, J., Debyser, Z., Agbandje‐McKenna, M., & Wilson, J. M. (2009) · Gene Therapy · doi:10.1038/gt.2009.101 · Cited by 72 · cited 1× · see citing works
“2, a novel vector with improved transduction in mouse airways, was generated via targeted single amino acid changes to AAV6 [ 107 , 108 ].”
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“Tyrosine mutations of different serotypes also demonstrate improved transduction of mesenchymal stem cells [ 113 ] and the mouse brain [ 117 , 118 ].”
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“Indeed, moderate success has been achieved by coating capsids with poly(ethylene) glycol [65], poly-[N-(2-hydroxypropyl) methacrylamide] [66], and α-dicarbonyl compounds [67].”
BackgroundJacques, S. J., Ahmed, Z., Forbes, A., Douglas, M. R., Vigenswara, V., Berry, M., & Logan, A. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.03.002 · Cited by 61 · cited 5× · see citing works
“AAV8 retains its tropism for large-diameter DRG neurons after intraparenchymal injection [39].”
BackgroundInfluentialMicroRNA-Restricted Transgene Expression in the Retina
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“However, binding sites for the RPE-specifi c miR-204 can block AAV5-mediated gene expression in RPE cells, resulting in PR-specifi c expression [ 130 ].”
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“Although initial experiments focused on the insertion of small peptides (5–15 amino acids), later studies have shown that insertions of full length proteins, such as GFP or mCherry, can also be tolerated without loss of virus function [78, 80].”
BackgroundDirected evolution of adeno-associated virus for glioma cell transduction
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“To date, improved targeting of skeletal muscle [81, 82], cardiac muscle [83], vasculature [84– 86], lung [87, 88], diseased brain endothelial cells [89], retina [90], ovarian cancer cells [91] and breast cancer cells [88] has been reported.”
BackgroundChen, S., Sanmiguel, J. C., Lock, M. W., McMenamin, D., Draper, C., Limberis, M. P., Kassim, S. H., Somanathan, S., Bell, P. L., Johnston, J., et al. (2013) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2013.082 · Cited by 43 · see citing works
Glycated AAV vectors: chemical redirection of viral tissue tropism
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“Indeed, moderate success has been achieved by coating capsids with poly(ethylene) glycol [65], poly-[N-(2-hydroxypropyl) methacrylamide] [66], and α-dicarbonyl compounds [67].”
BackgroundEngineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions
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“To date, improved targeting of skeletal muscle [ 81 , 82 ], cardiac muscle [ 83 ], vasculature [ 84 – 86 ], lung [ 87 , 88 ], diseased brain endothelial cells [ 89 ], retina [ 90 ], ovarian cancer cells [ 91 ] and breast cancer cells [ 88 ] has been reported.”
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“Further, AAVs 1 and 5 demonstrate greater retrograde transduction of brainstem than AAVs 2, 8, or 9 following injection of the transected spinal cord [59].”
BackgroundReceptors and tropisms of envelope viruses
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“[ 61 , 62 ]).”
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“8 kb neuron-specifi c enolase promoter [ 121 ], the 470 bp human synapsin-1 promoter [ 120 , 122 ], the 229 bp MeCP2 promoter [ 123 ], and the 2 kb herpes simplex virus 1 latency associated transcript promoter [ 124 ] can all drive neuron-specifi c gene expression.”
BackgroundSelf-citationGene Delivery to the Mouse Brain with Adeno-Associated Virus
Passini, M. A., Watson, D. J., & Wolfe, J. H. N. (2004) · Humana Press eBooks · doi:10.1385/1-59259-650-9:225 · Cited by 32 · cited 1× · see citing works
“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].”
BackgroundSelf-citationAdeno-associated virus serotype-9 efficiently transduces the retinal outer plexiform layer.
Lei, B., Zhang, K., Yue, Y., Ghosh, A., & Duan, D. (2009) · PubMed Central · Cited by 24 · see citing works
Efficient gene transfer into neurons in monkey brain by adeno-associated virus 8
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Improved Adeno-associated Viral Gene Transfer to Murine Glioma
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“Tyrosine mutations of different serotypes also demonstrate improved transduction of mesenchymal stem cells [ 113 ] and the mouse brain [ 117 , 118 ].”
BackgroundPilz, I. H., Pasquale, G. D., Rzadzinska, A. K., Leppla, S. H., & Chiorini, J. A. (2012) · Virology · doi:10.1016/j.virol.2012.03.004 · Cited by 11 · cited 13× · see citing works
“In primary cultures of rat nervous cells, AAV5 appears to possess a strong glial tropism, and gene expression rarely colocalizes with the neuronal marker Methods Mol Biol.”
BackgroundInfluentialComparison of AAV2 and AAV5 in gene transfer in the injured spinal cord of mice
Peng, S.-P., Kügler, S., Ma, Z.-K., Shen, Y., & Schachner, M. (2011) · Neuroreport · doi:10.1097/wnr.0b013e328348bff5 · Cited by 8 · cited 1× · see citing works
“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].”
BackgroundAn acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery
Lee, N., Falk, D. J., Byrne, B. J., Conlon, T. J., Clement, N., Porvasnik, S., Jorgensen, M., Potter, M., Erger, K. E., Watson, R., et al. (2012) · Genetic Vaccines and Therapy · doi:10.1186/1479-0556-10-3 · Cited by 5 · cited 1× · see citing works
“To date, improved targeting of skeletal muscle [81, 82], cardiac muscle [83], vasculature [84– 86], lung [87, 88], diseased brain endothelial cells [89], retina [90], ovarian cancer cells [91] and breast cancer cells [88] has been reported.”
Background
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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 · see citing works
“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 368 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
Liguore, W. A., Domire, J. S., Button, D. A., Wang, Y., Dufour, B. D., Srinivasan, S., & McBride, J. L. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.07.017 · Cited by 148 · see citing works
Lights, fiber, action! A primer on in vivo fiber photometry
Simpson, E. H., Akam, T. E., Patriarchi, T., Blanco-Pozo, M., Burgeno, L. M., Mohebi, A., Cragg, S. J., & Walton, M. E. (2023) · Neuron · doi:10.1016/j.neuron.2023.11.016 · Cited by 150 · see citing works
“81,88 One tool available to help identify an appropriate serotype, promoter, and titer for AAV vectors for a specific experiment is the AAV Data Hub hosted by Addgene (a popular source for viral vectors).”
Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions
Drag, S., Dotiwala, F., & Upadhyay, A. K. (2023) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.64.7.39 · Cited by 145 · see citing works
Recent progress and considerations for AAV gene therapies targeting the central nervous system
Lykken, E. A., Shyng, C., Edwards, R. J., Rozenberg, A. J., & Gray, S. J. (2018) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-018-9234-0 · Cited by 140 · see citing works
“Moving forward, future research studies could feasibly combine rational design and directed evolution methodologies [8, 57].”
BackgroundAcoustically targeted chemogenetics for the non-invasive control of neural circuits
Szablowski, J. O., Lee‐Gosselin, A., Lue, B., Malounda, D., & Shapiro, M. G. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0258-2 · Cited by 127 · see citing works
Gene therapy and genome surgery in the retina
DiCarlo, J. E., Mahajan, V. B., & Tsang, S. H. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120429 · Cited by 127 · see citing works
Adeno-Associated Viral Vectors in Neuroscience Research
Haggerty, D. L., Grecco, G. G., Reeves, K. C., & Atwood, B. K. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.11.012 · Cited by 123 · see citing works
“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 105 · see citing works
Emerging Gene Therapies for Genetic Hearing Loss
Ahmed, H., Shubina-Oleinik, O., & Holt, J. R. (2017) · Journal of the Association for Research in Otolaryngology · doi:10.1007/s10162-017-0634-8 · Cited by 104 · see citing works
“…of transduction (Rabinowitz and Samulski 2000; Zincarelli et al. 2008; Yu et al. 2009; Geguchadze et al. 2012; Aschauer et al. 2013; Sallach et al. 2014; Zinn et al. 2015; Castle et al. 2016; Mao et al. 2016; Marsic and Zolotukhin 2016; Payne et al. 2016; Sayroo et al. 2016; De Silva et al. 2016).”
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 94 · see citing works
“Strategies such as directed evolution are also expediting the generation of AAV serotypes with a predilection for specific retinal cell types (59,60).”
BackgroundPipe, S. W., Leebeek, F. W. G., Ferreira, V., Sawyer, E. K., & Pasi, J. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.08.015 · Cited by 92 · see citing works
Zhang, Q., Lee, W.-C. A., Paul, D. L., & Ginty, D. D. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0358-7 · Cited by 91 · see citing works
Advances with RNAi-Based Therapy for Hepatitis B Virus Infection
van den Berg, F. T., Limani, S. W., Mnyandu, N., Maepa, M. B., Ely, A., & Arbuthnot, P. B. (2020) · Viruses · doi:10.3390/v12080851 · Cited by 87 · see citing works
“AAV8 is hepatotropic, while AAV5 efficiently targets cells in the brain [108].”
BackgroundWang, Z., Maunze, B., Wang, Y., Tsoulfas, P., & Blackmore, M. G. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1196-18.2018 · Cited by 86 · see citing works
“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
Yang, M., Sunderland, K. S., & Mao, C. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00100 · Cited by 68 · see citing works
Weiss, A. R., Liguore, W. A., Domire, J. S., Button, D. A., & McBride, J. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-63559-7 · Cited by 67 · see citing works
Vectors and Gene Delivery to the Retina
Planul, A., & Dalkara, D. (2017) · Annual Review of Vision Science · doi:10.1146/annurev-vision-102016-061413 · Cited by 67 · see citing works
“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?
Wang, Y., Bruggeman, K. F., Franks, S. J., Gautam, V., Hodgetts, S. I., Harvey, A. R., Williams, R. J., & Nisbet, D. R. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202001238 · Cited by 66 · see citing works
Basurco, L., Abellanas, M. A., Ayerra, L., Conde, E., Vinueza‐Gavilanes, R., Luquin, E., Vales, Á., Vilas, A., Martín‐Úriz, P. S., Tamayo, I., et al. (2022) · Glia · doi:10.1002/glia.24295 · Cited by 64 · see citing works
Daci, R., & Flotte, T. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021050 · Cited by 68 · see citing works
“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 · see citing works
Adeno-Associated Virus Vector for Central Nervous System Gene Therapy
Zhu, D., Schieferecke, A. J., Lopez, P. A., & Schaffer, D. V. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.03.010 · Cited by 56 · see citing works
Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease
Cain, J. T., Likhite, S., White, K. A., Timm, D. J., Davis, S. S., Johnson, T. B., Dennys-Rivers, C. N., Rinaldi, F., Motti, D., Corcoran, S., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.06.015 · Cited by 53 · see citing works
“There are many AAV serotypes, including recombinant AAV serotypes, which differ in their tropism (reviewed in Castle et al.(33)).”
BackgroundMandel, R. J., Marmion, D. J., Kirik, D., Chu, Y., Heindel, C., McCown, T., Gray, S. J., & Kordower, J. H. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0451-7 · Cited by 56 · see citing works
“examples where the tropism of a given rAAV capsid does not remain consistent in rodents and higher animals have been described [7].”
Nair, R. R., Blankvoort, S., Lagartos-Donate, M. J., & Kentros, C. G. (2020) · iScience · doi:10.1016/j.isci.2020.100888 · Cited by 56 · see citing works
Lonser, R. R., Akhter, A. S., Ząbek, M., Elder, J. B., & Bankiewicz, K. S. (2020) · Journal of neurosurgery · doi:10.3171/2020.4.jns20701 · Cited by 54 · see citing works
Rittiner, J. E., Moncalvo, M., Chiba‐Falek, O., & Kantor, B. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00148 · Cited by 51 · see citing works
“Another method to expand AAV tropism is to create hybrid capsids derived from multiple serotypes (reviewed in Castle et al., 2016).”
MethodViral Tools for Neural Circuit Tracing
Liu, Q. L., Wu, Y., Wang, H., Jia, F., & Xu, F. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00949-z · Cited by 51 · see citing works
“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 52 · see citing works
“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 · see citing works
“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 49 · see citing works
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 46 · see citing works
“, neurons, astrocytes, NSPCs, and oligodendrocytes [85,86].”
Optimized Adeno-Associated Virus Vectors for Efficient Transduction of Human Retinal Organoids
Völkner, M., Pavlou, M., Büning, H., Michalakis, S., & Karl, M. (2021) · Human Gene Therapy · doi:10.1089/hum.2020.321 · Cited by 39 · see citing works
“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
Moghadam, F., LeGraw, R., Velazquez, J. J., Yeo, N. C., Xu, C., Park, J. H., Chavez, A., Ebrahimkhani, M. R., & Kiani, S. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0563-3 · Cited by 38 · see citing works
Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors
Hamann, M. V., Beschorner, N., Vu, X., Hauber, I., Lange, U. C., Traenkle, B., Kaiser, P. D., Foth, D., Schneider, C., Büning, H., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0261269 · Cited by 36 · see citing works
Gene therapy for Parkinson’s disease: contemporary practice and emerging concepts
Merola, A., Laar, A. D. V., Lonser, R. R., & Bankiewicz, K. S. (2020) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1763794 · Cited by 36 · see citing works
“The development of specific viral vectors serotypes is in clinical trials to optimize the tropism toward specific cell types, and strategies for capsid modifications are in an advanced stage of development to effectively steer vectors to target tissue from less invasive routes of administration [89,90].”
BackgroundThe neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer’s disease
Qureshi, Y. H., Berman, D. E., Marsh, S., Klein, R., Patel, V., Simoes, S., Kannan, S., Petsko, G., Stevens, B., & Small, S. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110262 · Cited by 29 · see citing works
Chemogenetics: Beyond Lesions and Electrodes
Poth, K. M., Texakalidis, P., & Boulis, N. M. (2021) · Neurosurgery · doi:10.1093/neuros/nyab147 · Cited by 31 · see citing works
Ozawa, A., & Arakawa, H. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113234 · Cited by 28 · see citing works
Lighting Up Neural Circuits by Viral Tracing
Qiu, L., Zhang, B., & Gao, Z. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00860-7 · Cited by 31 · see citing works
“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 · see citing works
“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 · see citing works
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 28 · see citing works
“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 29 · see citing works
Zhou, L., Wang, Y., Xu, Y., Zhang, Y., & Zhu, C. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03232-2 · Cited by 26 · see citing works
“…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 26 · see citing works
“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 · see citing works
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 26 · see citing works
“…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 25 · see citing works
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 23 · see citing works
“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 23 · see citing works
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 23 · see citing works
“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 · see citing works
Concepts and Strategies in Retinal Gene Therapy
Aguirre, G. D. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22978 · Cited by 24 · see citing works
“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 · see citing works
“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 21 · see citing works
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 · see citing works
“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 20 · see citing works
“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 18 · see citing works
“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 18 · see citing works
“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 18 · see citing works
A Matter of Genes: The Hurdles of Gene Therapy for Epilepsy
Ingusci, S., Cattaneo, S., Verlengia, G., Zucchini, S., & Simonato, M. (2019) · Epilepsy Currents · doi:10.1177/1535759718822846 · Cited by 15 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“…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 17 · see citing works
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 · see citing works
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 · see citing works
“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 13 · see citing works
“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 · see citing works
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 · see citing works
“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 11 · see citing works
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 · see citing works
“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 10 · see citing works
“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
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Viral Vector Delivery of DREADDs for CNS Therapy
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Cell-Based Therapies: Strategies for RegenerationPreprint
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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 9 · see citing works
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 · see citing works
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 · see citing works
Acoustically Targeted Chemogenetics for Noninvasive Control of Neural CircuitsPreprint
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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 8 · see citing works
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 7 · see citing works
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 · see citing works
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“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].”
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“[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 · see citing works
“21,22 AAVrh8, 9, and rh10 have been reported to transduce genes throughout the central nervous system when administered intravenously.”
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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 7 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 6 · see citing works
- 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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