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Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Open accessAbstract
Delivery of genes to the brain and spinal cord across the blood-brain barrier (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through the facial vein results in extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with limited neuronal transduction. This approach may enable the development of gene therapies for a range of neurodegenerative diseases, such as spinal muscular atrophy, through targeting of motor neurons, and amyotrophic lateral sclerosis, through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies.
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“In addition, AAV9 vectors have the unique ability to cross the blood–brain-barrier and target the brain upon intravenous injection in adult mice and cats (Duque et al, 2009; Foust et al, 2009).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Foust et al, 2009
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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“Immunohistochemistry with anti-eGFP antibodies at 1 month PI, showed a viral transduction efficiency of 20–50% of eGFP-positive cells depending on the tissue (Supporting Information Fig S1E and F) (Foust et al, 2009; Inagaki et al, 2006; Zincarelli et al, 2008).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Foust et al, 2009
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“AAV9 can cross the blood–brain barrier and transduce both neurons and astrocytes after intravenous administration.7,10–11”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [11]
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“AAV8 and AAV5 transduce a significantly greater area of the CNS in comparison with AAV2”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [11]
Experimental — accuracy not yet measuredIn the citing paper
“It was confirmed in SMA murine models that systemically delivered self-complementary AAV9 (scAAV9) crossed the blood brain barrier and achieved high levels of neuronal transduction.9,10”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [9]
In the citing paper
“The discovery of newer AAV capsids, such as AAV9, have permitted a much wider degree of gene transfer than multiple stereotaxic injections.9,10,67, 68, 69”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [9]
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Citations
Cites
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Cited by
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Items 601–700 of 1,001
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Mijanović, O., Branković, A., Borovjagin, A. V., Butnaru, D. V., Bezrukov, E. A., Sukhanov, R. B., Shpichka, A. I., Timashev, P. S., & Ulasov, I. V. (2020) · Viruses · doi:10.3390/v12040460 · Cited by 32
Intramuscular Delivery of Gene Therapy for Targeting the Nervous System
Tosolini, A. P., & Sleigh, J. N. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00129 · Cited by 32
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Ding, G., Shao, Q., Haiyan, Y., Liu, J., Li, Y., Wang, B., Sang, H., Li, D., Bing, A., Hou, Y., et al. (2022) · Pathogens · doi:10.3390/pathogens11101200 · Cited by 32
Ali, J. H., & Walter, M. (2023) · Cancer Cell International · doi:10.1186/s12935-023-03041-2 · Cited by 36
“For example, AAV9 has been shown to induce efficient transduction in a broad range of tissues, with high tropism for liver, heart, and skeletal muscle [213] and can even cross the blood–brain ‐ barrier [214, 215].”
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BackgroundInfluentialHarkins, A. L., Ambegaokar, P. P., & Keeler, A. M. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00435 · Cited by 36
“In spite of these advancements, many of these engineered AAVs have not yet been translated into the clinic but could be a promising tool for systemic AAV delivery to the CNS [42].”
Gene therapy then and now: A look back at changes in the field over the past 25 years
Wang, D., Stevens, G., & Flotte, T. R. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.02.040 · Cited by 34
“…clinical translation have been made since 2000, most notably the use of self-complementary AAV9 in newborns to cross the blood-brain barrier suf fi ciently to treat spinal muscular atrophy type 1, 119 which ultimately led to pivotal clinical studies 120,121 (Figure 4) and FDA approval of Zolgensma.”
Chen, S., Johnston, J., Sandhu, A., Bish, L. T., Hovhannisyan, R. H., Jno-Charles, O. C., Sweeney, H. L., & Wilson, J. M. (2013) · Human Gene Therapy Methods · doi:10.1089/hgtb.2012.129 · Cited by 31
Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery
Volak, A., LeRoy, S. G., Natasan, J.-S., Park, D. J., Cheah, P.-S., Maus, A., Fitzpatrick, Z., Hudry, E., Pinkham, K., Gandhi, S., et al. (2018) · Journal of Neuro-Oncology · doi:10.1007/s11060-018-2889-2 · Cited by 31
Chemogenetics: Beyond Lesions and Electrodes
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Recent Advances in RNA Interference Therapeutics for CNS Diseases
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Salegio, E. A., Samaranch, L., Jenkins, R. W., Clarke, C. J., Lamarre, C., Beyer, J., Kells, A. P., Bringas, J., Sebastián, W. S., Richardson, R. M., et al. (2012) · Human Gene Therapy · doi:10.1089/hum.2012.052 · Cited by 31
“If this holds even with vectors that transduce nonneuronal cells, such as AAV9 (Foust et al., 2009; Gray et al., 2011), the difficulty of transducing sufficient numbers of cells in the brain of patients with NPDA to effect therapeutic benefit may prove too daunting a task.”
BackgroundLentiviral Vectors: A Powerful Tool to Target Astrocytes In Vivo
Delzor, A., Escartin, C., & Déglon, N. (2013) · Current Drug Targets · doi:10.2174/13894501113146660213 · Cited by 31
“Tail vein injection of self-complementary (sc) AAV9-CBA-GFP (chicken- actin promoter) in adult mice led to a robust transduction of astrocytes throughout the entire CNS whereas neuronal transduction was observed in neonatal mice [33].”
Gene Transfer to the CNS Using Recombinant Adeno‐Associated Virus
Stoica, L., Ahmed, S. S., Gao, G., & Sena‐Esteves, M. (2013) · Current Protocols in Microbiology · doi:10.1002/9780471729259.mc14d05s29 · Cited by 29
“Recently, rAAV9 and a few other vectors were shown to mediate widespread gene transfer to brain and spinal cord following systemic administration in neonatal and adult mice, cats, and monkeys (Foust et al., 2009; Cotugno et al., 2011; Gray et al., 2011; Zhang et al., 2011; Yang et al., 2012).”
BackgroundTolerance and resistance characteristics of microalgae Scenedesmus sp. LX1 to methylisothiazolinone
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Molecular Approaches for the Treatment of Pompe Disease
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Drug Delivery Strategies to Overcome the Blood–Brain Barrier (BBB)
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Lighting Up Neural Circuits by Viral Tracing
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“mostly via intravenous injection, provides a simpler and non-invasive alternative for virus delivery to the central and peripheral nervous systems [78, 79].”
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Crommentuijn, M. H. W., Kantar, R. S., Noske, D. P., Vandertop, W. P., Badr, C. E., Würdinger, T., Maguire, C. A., & Tannous, B. A. (2016) · Molecular Therapy — Oncolytics · doi:10.1038/mto.2016.17 · Cited by 30
“17 By restricting expression to mostly neurons in the brain, we likely lowered the overall transgene expression levels in the brain.”
BackgroundManagement of Leigh syndrome: Current status and new insights
Chen, L., Cui, Y., Jiang, D., Ma, C. Y., Tse, H., Hwu, W., & Lian, Q. (2017) · Clinical Genetics · doi:10.1111/cge.13139 · Cited by 32
“To gain more benefit, alternative administration routes should be tried, such as multiple sites of injection or systemic delivery.(63)”
BackgroundRecombinant adeno-associated Virus: Clinical Application and Development As a gene-therapy Vector
Xiao, P.-J., Lentz, T. B., & Samulski, R. J. (2012) · Therapeutic Delivery · doi:10.4155/tde.12.63 · Cited by 31
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“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.”
BackgroundInfluentialNeuronal replacement: Concepts, achievements, and call for caution
Götz, M., & Bocchi, R. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.03.014 · Cited by 27
“Thus, using AAV vectors for neuronal reprogramming offers a translational opportunity, especially because some serotypes, such as AAV9, can be systemically delivered and still be able to selectively target glial cells in the central nervous system [54,55].”
Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology
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“The AAV9 serotype, however, has been found to have the ability to efficiently cross the BBB when intravenously delivered to neonatal and adult mice [156].”
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“AAV9 was selected because of its tropism for the brain.(14) On the basis of prior studies of gene therapy for Pompe disease, a glycogen storage disorder caused by mutations in the a-glucosidase gene, immune modulation was used before, during, and after AAV administration to prevent immune responses against the vector…”
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“59 In mice, injection of AAV9-GFP into the fetal vitelline vessels at 16 days of gestation achieved stronger neuronal expression than injection into neonates via the superficial temporal vein.”
BackgroundPerspective on the Road toward Gene Therapy for Parkinson’s Disease
Blits, B., & Petry, H. (2017) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2016.00128 · Cited by 29
“In patients with PD, increased activity of the STN is mainly caused by a reduction of GABAergic input from the globus pallidus (Erlander et al., 1991; Obeso et al., 2000; Wichmann and DeLong, 2003).”
BackgroundGene therapy decreases seizures in a model of Incontinentia pigmenti
Dogbevia, G., Töllner, K., Körbelin, J., Bröer, S., Ridder, D. A., Graßhoff, H., Brandt, C., Wenzel, J., Straub, B. K., Trepel, M., et al. (2017) · Annals of Neurology · doi:10.1002/ana.24981 · Cited by 30
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“Intravenous injection of postnatal day 1 (P1) pups with AAV serotype 9 (AAV9) was recently shown to achieve high transduction of motor neurons [33, 43].”
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Meadows, A. S., Duncan, F. J., Camboni, M., Waligura, K., Montgomery, C. L., Zaraspe, K., Naughton, B. J., Bremer, W. G., Shilling, C. J., Walker, C. M., et al. (2015) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2015.132 · Cited by 28
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Genetic targeting of astrocytes to combat neurodegenerative disease
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“Several serotypes of AAVs (AAV2/1, AAV2/5, AAV2/8, AAV2/9) have been tested to have tropism for astrocytes (Foust et al., 2009; Tong et al., 2014; Hammond et al., 2017; Pignataro et al., 2017).”
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“B, can mediate CNS gene delivery when administered intravascularly (Duque et al., 2009; Foust et al., 2009; Gray et al., 2011; Yang et al., 2014; Choudhury et al., 2016; Deverman et al., 2016; Hudry et al., 2018).”
BackgroundMegalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy
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“B by the University of Pennsylvania Vector Core (Philadelphia, PA, USA).(9,62) Virus was provided by the Vector Core at titers of 6.”
MethodBrain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice
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“The efficacy of scFvD18 to interfere with prion propagation in vivo is susceptible to further improvement, considering that systemic administration of AAV9 leads to transduction in the spleen and in astrocytes throughout the entire CNS, with limited neuronal involvement.(24,25) Therefore it is conceivable to combine A…”
BackgroundMolecular, genetic and stem cell‐mediated therapeutic strategies for spinal muscular atrophy ( SMA )
Zanetta, C., Riboldi, G. M., Nizzardo, M., Simone, C., Faravelli, I., Bresolin, N., Comi, G. P., & Corti, S. P. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12224 · Cited by 28
“scAAV9 was shown to have tropism for motor neurons in neonatal animals when injected intravascularly [36].”
BackgroundGene therapy for lysosomal storage disorders
Gritti, A. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.582036 · Cited by 30
“In adults, it transduces almost exclusively astrocytes and brain blood vessels, although some neuronal transduction is also observed [134].”
BackgroundChen, S. K., Hawley, Z. C. E., Zavodszky, M. I., Hana, S., Ferretti, D., Grubor, B., Hawes, M. C., Xu, S., Hamann, S., Marsh, G., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.102057 · Cited by 27
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Prospects for the gene therapy of spinal muscular atrophy
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A primer to gene therapy: Progress, prospects, and problems
Zittersteijn, H. A., Gonçalves, M. A. F. V., & Hoeben, R. C. (2020) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12270 · Cited by 28
“In the case of the latter ATMP, pre-clinical studies in animal models revealed an unexpected capacity of AAV serotype 9 (AAV9) particles to pass through the blood-brain barrier and to transduce motor neurons in the spinal cord.(107) Subsequent clinical evaluation in 15 patients demonstrated that a single intravenous i…”
BackgroundGene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders
Davidson, B. L., Gao, G., Berry‐Kravis, E., Bradbury, A. M., Bönnemann, C. G., Buxbaum, J. D., Corcoran, G. R., Gray, S. J., Gray‐Edwards, H. L., Kleiman, R. J., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.05.014 · Cited by 27
“to using systemic delivery of the vector to achieve CNS tropism in NHPs and eventually in humans, including reduced CNS and high peripheral tissue tropism in NHPs and humans,(70,71) loss of transduction efficiency as well as a change in tropism with increased age of the host, and the high prevalence and titer of neutr…”
BackgroundMethodInfluentialGene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders
Gessler, D. J., & Gao, G. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3271-9_30 · Cited by 28
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“barrier and can induce expression in the brain.(22,29,30) Similarly, we have shown that intracardiac injection of an AAV9‐based vector resulted in the expression of GLUT1 in the murine brain.”
BackgroundDirect evidence for transport of RNA from the mouse brain to the germline and offspring
O’Brien, E. A., Ensbey, K. S., Day, B. W., Baldock, P. A. J., & Barry, G. (2020) · BMC Biology · doi:10.1186/s12915-020-00780-w · Cited by 28
Adeno-Associated Viral Vectors for Gene Therapy of Inherited Retinal Degenerations
Flannery, J. G., & Visel, M. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-080-9_25 · Cited by 26
Neurodegenerative Diseases: New Hopes and Perspectives
Bhat, M. A., & Dhaneshwar, S. S. (2023) · Current Molecular Medicine · doi:10.2174/1566524023666230907093451 · Cited by 29
Adeno-associated virus therapies: Pioneering solutions for human genetic diseases
Liu, D., Tian, L., Liu, L., Che, X., Li, X., Liu, C., & Wu, G. (2024) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2024.09.003 · Cited by 29
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“As an example, hyaluronan is present ECM of CNS cells, carriers having affinity towards hyaluronic acid receptors increase the possibility of cell attachments and their subsequent survival (Prajapati et al., 2024).”
InfluentialShen, F., Kuo, R., Milon-Camus, M., Han, Z., Jiang, L., Young, W. L., & Su, H. (2012) · Stroke · doi:10.1161/strokeaha.112.662965 · Cited by 26
Ohtsuka, Y., Kanagawa, M., Yu, C.-C., Ito, C., Chiyo, T., Kobayashi, K., Okada, T., Takeda, S., & Toda, T. (2015) · Scientific Reports · doi:10.1038/srep08316 · Cited by 26
In vivo methods for acute modulation of gene expression in the central nervous system
Cwetsch, A. W., Pinto, B., Savardi, A., & Cancedda, L. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.04.008 · Cited by 26
“, astrocytes and oligodendrocytes) in the brain in vivo (Foust et al., 2009; Lawlor et al., 2009).”
AAV9-DOK7 gene therapy reduces disease severity in Smn2B/- SMA model mice
Kaifer, K. A., Villalón, E., Smith, C. E., Simon, M. E., Marquez, J., Hopkins, A. E., Morcos, T. I., & Lorson, C. L. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.07.031 · Cited by 26
Systemic Treatment of Fabry Disease Using a Novel AAV9 Vector Expressing α-Galactosidase A
Biferi, M. G., Cohen-Tannoudji, M., García-Silva, A., Souto-Rodríguez, O., Viéitez, I., Millán, B. S., Fernández‐Carrera, A., Pérez-Márquez, T., Teijeira, S., Barrera, S., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.10.016 · Cited by 26
“Our approach was based on the systemic injection of an AAV9, which demonstrated tropism for nervous tissue and the ability to cross the BBB.21,22 We found that systemic administration of the newly generated vector mediated widespread a-GalA expression and restored its function in the CNS and in multiple tissues of a k…”
MethodHong, S.-A., Seo, J. H., Wi, S., Jung, E. S., Yu, J., Hwang, G., Yu, J. H., Baek, A., Park, S., Bae, S., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.05.022 · Cited by 27
Hutt, 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
Mani, S., Jindal, D., & Singh, M. (2022) · Current Gene Therapy · doi:10.2174/1566523222666220328142427 · Cited by 30
Reilly, A., Deguise, M., Beauvais, A., Yaworski, R., Thebault, S., Tessier, D. R., Tabard‐Cossa, V., Hensel, N., Schneider, B. L., & Kothary, R. (2022) · Gene Therapy · doi:10.1038/s41434-022-00338-1 · Cited by 26
“This gene therapy treatment is administered as a one-time intravenous (IV) injection, aiming to induce long-term expression of SMN protein in the periphery as well as the CNS [23, 24].”
MethodModulating the Excitability of Olfactory Output Neurons Affects Whole-Body Metabolism
Kolling, L. J., Tatti, R., Lowry, T. W., Loeven, A. M., Fadool, J. M., & Fadool, D. A. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.0190-22.2022 · Cited by 25
“To achieve maximal transduction of M/TCs across the OB, we further optimized AAV9 delivery by using a RO intravenous injection (Foust et al., 2009; Yardeni et al., 2011) to deliver our packaged sgRNA1 as AAV9-hSyn-mCherry-U6-sgRNA1 (Fig.”
MethodNeuro-Immuno-Gene- and Genome-Editing-Therapy for Alzheimer’s Disease: Are We There Yet?
Raikwar, S. P., Thangavel, R., Dubova, I., Ahmed, M. E., Selvakumar, G. P., Kempuraj, D., Zaheer, S. A., Iyer, S. S., & Zaheer, A. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180422 · Cited by 27
Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges
Haque, U. S., & Yokota, T. (2024) · Genes · doi:10.3390/genes15080999 · Cited by 27
“Onasemnogene abeparvovec is a gene therapy that uses an scAAV9 vector to cross the blood–brain barrier and deliver therapeutic genes [74].”
BackgroundDuncan, F. J., Naughton, B. J., Zaraspe, K., Murrey, D. A., Meadows, A. S., Clark, K. R., Newsom, D. E., White, P., Fu, H., & McCarty, D. M. (2015) · Molecular Therapy · doi:10.1038/mt.2015.9 · Cited by 25
Gene Therapies for Polyglutamine Diseases
Matos, C. A., Carmona, V., Vijayakumar, U. G., Lopes, S., Albuquerque, P., Conceição, M., Nobre, R. J., Nóbrega, C., & de Almeida, L. P. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-71779-1_20 · Cited by 25
Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice
Kray, K. M., McGovern, V. L., Chugh, D., Arnold, W. D., & Burghes, A. H. M. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105488 · Cited by 26
Ramirez, S. H., Hale, J. F., McCarthy, S., Cardenas, C. L. L., Dona, K. N. U. G., Hanlon, K. S., Hudry, E., de la Cruz, D., Ng, C., Das, S., et al. (2023) · Human Gene Therapy · doi:10.1089/hum.2022.211 · Cited by 25
Liu, C., Liu, Q., Song, L., Gu, Y., Jie, J., Bai, X., & Yang, Y. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.125328 · Cited by 25
“Compared with other viral vectors, such as adenovirus and lentivirus, AAV vector is highly safe, has a wide range of host cells, and can be used to express exogenous genes for a long time period in vivo([32-33]).”
BackgroundGene therapy for amyotrophic lateral sclerosis
Federici, T., & Boulis, N. M. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.08.018 · Cited by 25
Liu, Q., Demirel, E., Chen, Y., Gong, T., Zhang, X., & Chen, Y. (2019) · Journal of Applied Polymer Science · doi:10.1002/app.47685 · Cited by 26
Ellsworth, J. L., Gingras, J., Smith, L. J., Rubin, H. L., Seabrook, T. A., Patel, K., Zapata, N., Olivieri, K. C., O’Callaghan, M., Chlipala, E. A., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225582 · Cited by 25
“A property of Clade F vectors is the ability to traverse the blood-brain-barrier (BBB) following intravascular administration, resulting in transduction of neurons and glia in neonatal and adult mice [15, 16], rats [17], cats [16] and in nonhuman primates [18, 19].”
BackgroundInfluentialBAAV Transcytosis Requires an Interaction with β-1-4 Linked- Glucosamine and gp96
Pasquale, G. D., Kaludov, N. K., Agbandje‐McKenna, M., & Chiorini, J. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009336 · Cited by 27
“As described above, transcytosis activity has been demonstrated in BAAV, AAV4, AAV5 and has been proposed to occur in 2 others; AAV8 and AAV9 [11,16–19].”
BackgroundCrommentuijn, M. H. W., Maguire, C. A., Niers, J. M., Vandertop, W. P., Badr, C. E., Wurdinger, T. D., & Tannous, B. A. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.11.011 · Cited by 25
Over the barrier and through the blood: To CNS delivery we go
Foust, K. D., & Kaspar, B. K. (2009) · Cell Cycle · doi:10.4161/cc.8.24.10245 · Cited by 25
Self-citationAhmed, S. S., Schattgen, S. A., Frakes, A. E., Sikoglu, E. M., Su, Q., Li, J., Hampton, T. G., Denninger, A. R., Kirschner, D. A., Kaspar, B., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.68 · Cited by 24
Self-citationNeurosurgical gene therapy for central nervous system diseases
Patel, R. V., Nanda, P., & Richardson, R. M. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00434 · Cited by 23
“Thus far, the NHP derived capsid variants used in CNS clinical trials are AAVrh.8 and AAVrh.10 which are able to cross the blood brain barrier following intravenous delivery and improve CNS transduction while limiting peripheral tissue uptake [66,67].”
MethodGene therapy for the neurological manifestations in lysosomal storage disorders
Cheng, S. H. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r047175 · Cited by 25
Disease Modeling and Therapeutic Strategies in CMT2A: State of the Art
Barbullushi, K., Abati, E., Rizzo, F., Bresolin, N., Comi, G. P., & Corti, S. P. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1533-2 · Cited by 23
Lot-to-Lot Variation in Adeno-Associated Virus Serotype 9 (AAV9) Preparations
O'Connor, D. M., Lutomski, C. A., Jarrold, M. F., Boulis, N. M., & Donsante, A. (2019) · Human Gene Therapy Methods · doi:10.1089/hgtb.2019.105 · Cited by 23
Liao, X.-H., Avalos, P., Shelest, O., Ofan, R., Shilo, M., Bresee, C. J., Likhite, S. B., Vit, J., Heuer, H., Kaspar, B. K., et al. (2022) · Thyroid · doi:10.1089/thy.2022.0034 · Cited by 24
“Importantly, it has been shown that AAV9 IV-delivery can cross the BBB and efficiently infect CNS cells (27).”
Self-citationLin, Y., Li, C., Wang, W., Li, J., Huang, C., Zheng, X., Liu, Z., Song, X., Chen, Y., Gao, J., et al. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1115348 · Cited by 23
“Because the blood-brain barrier of newborn piglets is not fully established, AAV-9 virus has been proved that it can cross the blood-brain barrier relatively easily and can be distributed widely in the brain after intravenous injection of newborn pigs (Foust et al., 2009).”
BackgroundKawabata, H., Konno, A., Matsuzaki, Y., & Hirai, H. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.02.016 · Cited by 24
Gene therapy in glioblastoma multiforme: Can it be a role changer?
Rayati, M., Mansouri, V., & Ahmadbeigi, N. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27087 · Cited by 27
“This revolution was underpinned by their capacity to traverse the BBB, rendering systemic injection more efficacious and supplanting the need for invasive local methodologies [93 – 95].”
MethodKornum, B. R., Stott, S., Mattsson, B., Wisman, L. A. B., Ettrup, A., Hermening, S., Knudsen, G. M., & Kirik, D. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.12.009 · Cited by 23
“, 2008) and intravenous injection of rAAV9 in newborn mice (Foust et al., 2009).”
BackgroundCurrent prospects and challenges for epilepsy gene therapy
Weinberg, M. S., & McCown, T. J. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.10.003 · Cited by 24
“…expression is driven by a constitutive promoter, direct CNS injection of AAV9 results in almost exclusive neuronal transduction (Klein, et al., 2008), whereas after peripheral administration, AAV9 vectors transduce both neurons and astrocytes in the CNS (Foust et al., 2009; Duque et al., 2009).”
BackgroundMachida, A., Kuwahara, H., Mayra, A., Kubodera, T., Hirai, T., Sunaga, F., Tajiri, M., Hirai, Y., Shimada, T., Mizusawa, H., et al. (2013) · Molecular Pain · doi:10.1186/1744-8069-9-36 · Cited by 25
“Terzi D, Zachariou V: Adeno-associated virus-mediated gene delivery approaches for the treatment of CNS disorders.”
BackgroundResultInfluentialAdeno Associated Viral Vector Delivered RNAi for Gene Therapy of SOD1 Amyotrophic Lateral Sclerosis
Stoica, L., & Sena‐Esteves, M. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00056 · Cited by 24
“REDUCTION OF SOD1 IS NECESSARY IN”
BackgroundSystemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy
Yi, H., Zhang, Q., Brooks, E. D., Yang, C., Thurberg, B. L., Kishnani, P. S., & Sun, B. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.099 · Cited by 24
Giorgio, E., Lorenzati, M., Cervo, P. R. D. V., Brussino, A., Cernigoj, M., Sala, E. D., Stella, A. B., Ferrero, M., Caiazzo, M., Capellari, S., et al. (2019) · Brain · doi:10.1093/brain/awz139 · Cited by 26
Liu, T., Wen, H., Li, H., Xu, H., Xiao, N., Liu, R., Chen, L., Sun, Y., Song, L., Bai, C., et al. (2020) · Hypertension · doi:10.1161/hypertensionaha.119.14167 · Cited by 24
“AAV9-FGF23 and AAV9-GFP vectors were intravenously injected 3 weeks before OA treatment and Ang II infusion in wild-type mice.(34) Overexpression of FGF23 in whole heart tissue was verified by fluorescence microscopy and Western blotting (Figures S5 and S6).”
MethodSponge-mediated lentivirus delivery to acute and chronic spinal cord injuries
Thomas, A. M., Palma, J. L., & Shea, L. D. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.02.032 · Cited by 24
“Furthermore, the off-site implantation of these therapies requires increased dosages to achieve therapeutic effects [43, 44], which could potentially trigger an immune response.”
BackgroundBarkats, M. (2020) · médecine/sciences · doi:10.1051/medsci/2020010 · Cited by 24
Candidate Diseases for Prenatal Gene Therapy
David, A. L., & Waddington, S. N. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-873-3_2 · Cited by 24
O’Connor, D. M. A., & Boulis, N. M. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.04.079 · Cited by 22
Xie, B., Wang, X., Pan, Y., Jiang, G., Feng, J., & Lin, Y. (2020) · Theranostics · doi:10.7150/thno.46992 · Cited by 23
“However, this BBB penetration occurs only at a very high virus load and with limited CNS transduction efficiency [8-10].”
BackgroundViral gene therapy for paediatric neurological diseases: progress to clinical reality
Privolizzi, R., Chu, W. S., Tijani, M., & Ng, J. (2021) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14885 · Cited by 21
WWOX-Related Neurodevelopmental Disorders: Models and Future Perspectives
Steinberg, D. J., & Aqeilan, R. I. (2021) · Cells · doi:10.3390/cells10113082 · Cited by 22
Metadata
- Authors
- Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K.
- Affiliations
- Nationwide Children's Hospital (US)
- Corresponding author
- Kaspar, Brian K
- Venue
- Nature Biotechnology
- Published
- 2008-12-21
- Volume
- 27
- Issue
- 1
- Pages
- 59-65
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC2895694
- OpenAlex
- W2166739815
- Cited by
- 1,456
- References
- 38
- Citations by year
- 2026: 75 · 2025: 91 · 2024: 107 · 2023: 94 · 2022: 87 · 2021: 101 · 2020: 105 · 2019: 90 · 2018: 100 · 2017: 81 · 2016: 79 · 2015: 78 · 2014: 74 · 2013: 88 · 2012: 54
- FWCI
- 28.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R21EY018491)
- National Institute of Neurological Disorders and Stroke (R21NS064328, R01NS064492)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- AAV9, adeno-associated virus, blood-brain barrier, astrocytes, motor neurons, neonatal neurons, spinal cord, dorsal root ganglia, gene therapy, spinal muscular atrophy, amyotrophic lateral sclerosis
- MeSH terms
- Dependovirus, Animals, Astrocytes, Ganglia, Spinal, Genetic Vectors, Hippocampus, Mice, Inbred C57BL, Muscular Atrophy, Spinal, Neurons, In Situ Hybridization, Gene Transfer Techniques, Transgenes, Neocortex, Green Fluorescent Proteins, Mice
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