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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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“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]
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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“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
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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]
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“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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ResultClades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues
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Cited by
Sorted by citations
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Adeno-associated virus vectors and neurotoxicity—lessons from preclinical and human studies
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Bossuyt, J., Herrewegen, Y. V. D., Nestor, L., Buckinx, A., Bundel, D. D., & Smolders, I. J. (2023) · Glia · doi:10.1002/glia.24390 · Cited by 44
Receptor–mediated transcytosis of macromolecules across the blood–brain barrier
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“…balanced, multiple interactions could be the age, species, and even intra-species differences that plague the translatability of capsids both at the overall brain tropism level and at the level of selective transduction of different cell types within the brain – examples include AAV9 [87], X1.”
BackgroundMitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins
C., M. A. Z., Moore, H. J., Smith, T. J. S., Powell, J. E., Ahsan, N. S., Zhang, S., & Gaj, T. (2023) · Nature Communications · doi:10.1038/s41467-023-42147-z · Cited by 36
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Self-citationPhysical positioning markedly enhances brain transduction after intrathecal AAV9 infusion
Castle, M. J., Cheng, Y., Asokan, A., & Tuszynski, M. H. (2018) · Science Advances · doi:10.1126/sciadv.aau9859 · Cited by 41
Long-Term Efficacy of AAV9-U7snRNA-Mediated Exon 51 Skipping in mdx52 Mice
Aupy, P., Zarrouki, F., Sandro, Q., Gastaldi, C., Buclez, P.-O., Mamchaoui, K., Garcı́a, L., Vaillend, C., & Goyenvalle, A. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.04.025 · Cited by 42
Antisense oligonucleotides and spinal muscular atrophy: skipping along: Figure 1.Preprint
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Prabhakar, S., Cheah, P.-S., Zhang, X., Zinter, M., Gianatasio, M. T., Hudry, E., Bronson, R. T., Kwiatkowski, D. J., Stemmer-Rachamimov, A. O., Maguire, C. A., et al. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.08.003 · Cited by 40
“Molecular Therapy: Methods & Cli tor, low toxicity, extensive biodistribution, and ability to cross the blood-brain barrier (BBB).(12,13)”
BackgroundXie, Q., Chen, X., Ma, H., Zhu, Y., Ma, Y., Jalinous, L., Cox, G. F., Weaver, F., Yang, J., Kennedy, Z., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00037-x · Cited by 41
“Compared to healthy carriers on Day 30, mice treated with the benchmark vector had signi fi cantly lower SMN expression in the CNS (brain and spinal cord; p < 0.01) and higher expression in the heart (69-fold) and quadricep muscles (35-fold).”
InfluentialSpinal Muscular Atrophy: Journeying From Bench to Bedside
Awano, T., Kim, J.-K., & Monani, U. R. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0293-y · Cited by 40
“In part, this is a consequence of the identification of new serotypes, for example adenoassociated virus (AAV)9, of the adenoassociated virus which are reported to efficiently penetrate BBB of neonatal mice and infect multiple cell types [102].”
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Muñoz-Lorente, M. A., Martínez, P., Tejera, Á., Whittemore, K., Moisés-Silva, A. C., Bosch, F., & Blasco, M. A. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007562 · Cited by 40
Chen, X., He, Y., Tian, Y., Wang, Y., Wu, Z., Lan, T., Wang, H., Cheng, K., & Xie, P. P. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.300 · Cited by 38
“15 Nevertheless, poor specificity of brain regions and low infection rates limit the application of this method in neuroscience.”
A Viral Toolbox of Genetically Encoded Fluorescent Synaptic Tags
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Gene Therapy in a Mouse Model of Niemann–Pick Disease Type C1
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“AAV9 is well known for its ability to cross the blood/brain barrier and distribute into the brain globally, targeting both neurons and astrocytes.(33,34) In the present study, we used the tyrosine-mutant AAV9/3 vector, which has been reported to significantly enhance gene delivery to the CNS.”
MethodIDS Crossing of the Blood-Brain Barrier Corrects CNS Defects in MPSII Mice
Polito, V. A., & Cosma, M. P. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.07.011 · Cited by 40
Li, X., Xu, H., Chen, S., Jiang, W., Afridi, S. K., Wang, Y., Ren, X., Zhao, Y., Lai, S., Qiu, X., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.07.017 · Cited by 39
György, B., & Maguire, C. A. (2017) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1488 · Cited by 44
“finally achieve widespread therapy to the CNS.(34,35) The original finding in mice has translated to nonhuman primates(36) and is now in clinical trials for spinal muscular atrophy (clinicaltrials.”
BackgroundSimpson, E. M., Korecki, A. J., Fornés, O., McGill, T. J., Vargas, J. L. C., Agostinone, J., Farkas, R. A., Hickmott, J. W., Lam, S. L., Mathelier, A., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.118 · Cited by 41
Gene therapy approaches targeting Schwann cells for demyelinating neuropathies
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Approaches to gene modulation therapy for ALS
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Ponomarev, A. S., Chulpanova, D. S., Yanygina, L. M., Solovyeva, V. V., & Rizvanov, A. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813743 · Cited by 43
“The self-complementary feature of the AAV9 vector in combination with the cytomegalovirus hybrid enhancer and the chicken beta-actin promoter ensures rapid and sustained expression of SMN1 [56].”
BackgroundFrom Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer’s Disease
Ortega, A., Chernicki, B. P., Ou, G., & Parmar, M. S. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04285-3 · Cited by 41
“Research interest has increasingly focused on evaluating BBB-penetrating AAV capsids [14, 82, 83].”
TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain
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“We first examined its distribution in postnatal mouse brains by intravenous injection of UBC-TDP-43 vector into P1 mouse pups (n 1⁄4 6), as the intravenous delivery of AAV9 vectorswouldallowthe transgene tocross the blood–brain barrier and target neurons and astrocytes in the brain (18,19).”
MethodAAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/−SMA model mice
Kaifer, K. A., Villalón, E., O’Brien, B. S., Sison, S. L., Smith, C. E., Simon, M. E., Marquez, J., O’Day, S., Hopkins, A. E., Neff, R., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz142 · Cited by 39
Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases
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“AAV9, a naturally discovered AAV from human livers, can cross the BBB, and this makes it a useful vehicle for targeting the brain via IV injection (Gao et al., 2004; Foust et al., 2009) even though it is not CNS specific and can also robustly transduce peripheral tissues (Zincarelli et al.”
BackgroundMiyake, N., Miyake, K., Asakawa, N., Yamamoto, M., & Shimada, T. (2014) · Gene Therapy · doi:10.1038/gt.2014.17 · Cited by 40
SMN deficiency does not induce oxidative stress in SMA iPSC-derived astrocytes or motor neurons
Patitucci, T. N., & Ebert, A. D. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv489 · Cited by 37
“ing the blood–brain barrier (9,14,15), evidence suggests treatments lose efficacywith disease progression leaving only a narrow therapeutic window (13,16,17).”
BackgroundAdeno-Associated Virus-Mediated MicroRNA Delivery and Therapeutics
Xie, J., Burt, D. R., & Gao, G. (2015) · Seminars in Liver Disease · doi:10.1055/s-0034-1397352 · Cited by 40
MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy
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Hadaczek, P., Stanek, L. M., Ciesielska, A., Sudhakar, V. R., Samaranch, L., Pivirotto, P., Bringas, J., O’Riordan, C. R., Mastis, B., Sebastián, W. S., et al. (2016) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2016.37 · Cited by 37
Development of Therapeutics for C9ORF72 ALS/FTD-Related Disorders
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Gene therapy for chronic pain management
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“29 Intravenous AAV9 has been shown to be more potent than other AAV serotypes to infect neuronal neurons in the CNS. 61 To overcome the package limitations of AAV, HSV-1 and LVs have been used in pain research.”
BackgroundGene therapy as an adjuvant treatment for malignant gliomas: from bench to bedside
Germano, I. M., & Binello, E. (2009) · Journal of Neuro-Oncology · doi:10.1007/s11060-009-9869-5 · Cited by 36
Osmon, K. J. L., Woodley, E., Thompson, P., Ong, K., Karumuthil‐Melethil, S., Keimel, J. G., Mark, B. L., Mahuran, D. J., Gray, S. J., & Walia, J. S. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.015 · Cited by 39
AAV1 is the optimal viral vector for optogenetic experiments in pigeons (Columba livia)
Rook, N., Tuff, J. M., Isparta, S., Masseck, O. A., Herlitze, S., Güntürkün, O., & Pusch, R. (2021) · Communications Biology · doi:10.1038/s42003-020-01595-9 · Cited by 40
Marcó, S., Haurigot, V., Jaén, M. L., Ribera, A., Sánchez, V., Molas, M., Garcia, M., León, X., Roca, C., Sánchez, X., et al. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.09.017 · Cited by 41
“Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS.”
MethodInfluentialAAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice
Palfi, A., Chadderton, N., Millington‐Ward, S., Post, I. J. M., Humphries, P., Kenna, P. F., & Farrar, G. J. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.03.016 · Cited by 37
Non-invasive optogenetics with ultrasound-mediated gene delivery and red-light excitation
Pouliopoulos, A. N., Murillo, M. F., Noel, R. L., Batts, A. J., Ji, R., Kwon, N., Yu, H. Y., Tong, C., Gelinas, J. N., Khodagholy, D., et al. (2022) · Brain stimulation · doi:10.1016/j.brs.2022.06.007 · Cited by 35
“Page 16 [35], and to widespread transduction when coupled with FUS treatment [36].”
BackgroundSong, R., Pekrun, K., Khan, T. A., Zhang, F., Paşca, S. P., & Kay, M. A. (2022) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2022.09.002 · Cited by 36
“There are also three additional amino acids (492S, 493A and 500Y) that are part of VR V and are shared only between AAV2 and AAV-DJ.”
BackgroundMethodInfluentialLin, Y., Roman, K., Foust, K. D., Kaspar, B. K., Bailey, M. T., & Stephens, R. L. (2011) · Pain Research and Treatment · doi:10.1155/2011/507029 · Cited by 36
Self-citationGene therapy for mitochondrial disorders
Keshavan, N., Minczuk, M. A., Viscomi, C. F., & Rahman, S. (2024) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12699 · Cited by 39
“122 However, pre-clinical studies 46,121 also indicated that brain targeting was inferior to spinal cord targeting via the IV route.”
BackgroundProgress of nanoparticle drug delivery system for the treatment of glioma
Lai, G., Wu, H., Yang, K., Hu, K., Yan, Z., Chen, X., Fu, F., Li, J., Xie, G., Wang, H., et al. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1403511 · Cited by 37
Słyk, Ż., Stachowiak, N., & Małecki, M. (2024) · Biomedicines · doi:10.3390/biomedicines12071523 · Cited by 40
Recent developments in gene therapy for Parkinson’s disease
Szunyogh, S., Carroll, E., & Wade‐Martins, R. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.030 · Cited by 39
“While not yet examined clinically, intravenous delivery of gene therapies using AAV9 in mice has been shown to trans-duce several brain regions, 100,104,105 suggesting that systemic delivery transfer through the BBB may be feasible.”
Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis
Wong, A. M. S., Rahim, A. A., Waddington, S. N., & Cooper, J. D. (2010) · Biochemical Society Transactions · doi:10.1042/bst0381484 · Cited by 35
Present and Future of Adeno Associated Virus Based Gene Therapy Approaches
Ortolano, S., Spuch, C., & Fernández-Balbuena, C. N. (2012) · Recent Patents on Endocrine Metabolic & Immune Drug Discovery · doi:10.2174/187221412799015245 · Cited by 38
Homs, J., Pagès, G., Ariza, L., Casas, C., Chillón, M., Navarro, X., & Bosch, A. (2014) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2013.7 · Cited by 36
Gene therapy to target ER stress in brain diseases
Valenzuela, V., Martínez, G., Duran-Aniotz, C. A., & Hetz, C. A. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.064 · Cited by 36
“…permeable BBB and transduction spreading, allowing efficient transduction of the nervous system by several administration routs (Foust et al., 2008; Foust et al., 2009; Gombash et al., 2014; Tanguy et al., 2015), a strategy that could be applied in the future to treat familial forms of…”
BackgroundMendoza, S. D., El-Shamayleh, Y., & Horwitz, G. D. (2017) · Journal of Neurophysiology · doi:10.1152/jn.00780.2016 · Cited by 38
“Nevertheless, anti-AAV9 titers exceeded anti-AAV5 titers in the sera we tested, an effect that cannot be explained by the concentrations of vector used in the assay.”
BackgroundInfluentialA bright future? Optogenetics in the periphery for pain research and therapy
Mickle, A. D., & Gereau, R. W. (2018) · Pain · doi:10.1097/j.pain.0000000000001329 · Cited by 37
“S have been shown to have higher tropism for dorsal root ganglion (DRG) neurons than other serotypes.(16,17,36,52,53,59,76,84,98,99,105,108,119) Moreover, it may be possible to exploit different serotypes to induce”
BackgroundMethodInfluentialGene-Based Approaches to Inherited Neurometabolic Diseases
Poletti, V., & Biffi, A. (2019) · Human Gene Therapy · doi:10.1089/hum.2019.190 · Cited by 35
“58 Finally, simultaneous injection of rAAV9-PPT1 in the brain and spinal cord of Ppt1-ko mice resulted in a significantly better therapeutic outcome than the direct vector delivery in a single region of the CNS, suggesting the relevance of targeting the whole CNS to achieve a significant therapeutic ef-ficacy in NCLs. 59…”
InfluentialLahey, H. G., Webber, C. J., Golebiowski, D., Izzo, C., Horn, E., Taghian, T., Rodríguez, P. M., Batista, A. R., Ellis, L. E., Hwang, M., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.06.021 · Cited by 37
“The CNS gene transfer efficiency and tropism of AAV9 delivered systemically in mice changes after the neonatal period where neuronal transduction is observed, to a predominantly astrocytic profile soon after birth.(38,39) The AAV9 neuronal tropism is unique to neonatal mice and has not been reproduced in other species…”
BackgroundDelivery Platforms for CRISPR/Cas9 Genome Editing of Glial Cells in the Central Nervous System
Meneghini, V., Peviani, M., Luciani, M., Zambonini, G., & Gritti, A. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.644319 · Cited by 36
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“This is in line with previous reports showing a high transduction efficiency of AAV9 for neuronal cells.(22,56) By contrast, AAV1_P5 and AAV9_A2 exhibited a selective tropism for the v-SVZ, mainly targeting NSCs/TAPs (SOX2/GFAP /S100B ) as well as ependymal cells (SOX2/S100B; Figures 2H and 2J).”
ResultNovel Adeno-associated Viruses Derived From Pig Tissues Transduce Most Major Organs in Mice
Bello, A., Chand, A., Aviles, J., Soule, G., Auricchio, A., & Kobinger, G. (2014) · Scientific Reports · doi:10.1038/srep06644 · Cited by 36
microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity
Horie, T., Nakao, T., Miyasaka, Y., Nishino, T., Matsumura, S., Nakazeki, F., Ide, Y., Kimura, M., Tsuji, S., Rodriguez, R. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21107-5 · Cited by 49
Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
Kagiava, A., Richter, J., Tryfonos, C., Leal-Julià, M., Sargiannidou, I., Christodoulou, C., Bosch, A., & Kleopa, K. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-02694-1 · Cited by 34
Structural basis of receptor usage by the engineered capsid AAV-PHP.eB
Jang, S., Shen, H. K., Ding, X., Miles, T. F., & Gradinaru, V. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.07.011 · Cited by 35
“In particular, the AAV9 serotype, which can penetrate the blood-brain barrier (BBB) and transduce the central nervous system (CNS), is a focus of intense study for the treatment of neurodegenerative diseases.(6,7) However, AAV9 has a broad tropism, targeting non-neuronal as well as neuronal cells, which has limited it…”
BackgroundMatuszek, Ż., Arbab, M., Kesavan, M., Hsu, A., Roy, J. C. L., Zhao, J., Yu, T., Weisburd, B., Newby, G. A., Doherty, N. J., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02172-8 · Cited by 35
Adeno-associated virus serotypes 9 and rh10 mediate strong neuronal transduction of the dog brain
Swain, G. P., Prociuk, M. L., Bagel, J. H., O’Donnell, P., Berger, K., Drobatz, K., Gurda, B. L., Haskins, M. E., Sands, M. S., & Vite, C. H. (2013) · Gene Therapy · doi:10.1038/gt.2013.54 · Cited by 34
Adeno‐associated virus‐based Alzheimer's disease mouse models and potential new therapeutic avenues
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“…is influenced by a number of factors including vector purity (Klein, Dayton, Tatom, Henderson, & Henning, 2008), maturity of the host CNS (Foust et al., 2009; von Jonquieres et al., 2013), species (Gray et al., 2011; Watakabe et al., 2015), and route of administration (Hocquemiller,…”
BackgroundViral vectors for gene delivery to the inner ear
Maguire, C. A., & Corey, D. P. (2020) · Hearing Research · doi:10.1016/j.heares.2020.107927 · Cited by 33
Ojala, K. S., Reedich, E. J., DiDonato, C. J., & Meriney, S. D. (2021) · Brain Sciences · doi:10.3390/brainsci11020194 · Cited by 37
“In addition to disease progression prior to treatment, this result is also attributed to an age-related switch in transduction efficiency from neurons to glia in mice [215].”
BackgroundKorecki, A. J., Vargas, J. L. C., Fornés, O., Agostinone, J., Farkas, R. A., Hickmott, J. W., Lam, S. L., Mathelier, A., Zhou, M., Wasserman, W. W., et al. (2021) · Gene Therapy · doi:10.1038/s41434-021-00227-z · Cited by 34
“We therefore limited use of adult intravenous delivery to MiniPromoters designed to target the BRB and BBB.”
BackgroundInfluentialA Review of Gene Therapy in Canine and Feline Models of Lysosomal Storage Disorders
Bradbury, A. M., Gurda, B. L., Casal, M. L., Ponder, K. P., Vite, C. H., & Haskins, M. E. (2015) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2015.002 · Cited by 36
“21,22 Animal models of LSDs provide an important intermediate to optimize gene therapy protocols and assess the safety and efficacy of therapy prior to initiating human clinical trials.”
Systemic scAAV9 variant mediates brain transduction in newborn rhesus macaques
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“The recent development of the viral-mediated delivery of genes has led to the identification of viruses capable of transducing developing cells and neuron”
BackgroundAdeno-associated virus and lentivirus vectors: a refined toolkit for the central nervous system
Blessing, D., & Déglon, N. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.08.004 · Cited by 36
“transduction of various tissues, and therefore requires very high doses of vector [16-18].”
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Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations
Kilpatrick, S., Irwin, C. L., & Singh, K. K. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02510-6 · Cited by 34
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Therapy development in spinal muscular atrophy
Sendtner, M. (2010) · Nature Neuroscience · doi:10.1038/nn.2565 · Cited by 33
“and by the recent report that these viruses are relatively selective for motor neurons after systemic injectio”
BackgroundSystemic AAV9-IFNβ gene delivery treats highly invasive glioblastoma
GuhaSarkar, D., Su, Q., Gao, G., & Sena‐Esteves, M. (2016) · Neuro-Oncology · doi:10.1093/neuonc/now097 · Cited by 33
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Additive amelioration of ALS by co‐targeting independent pathogenic mechanisms
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“Furthermore, recent reports demonstrate that AAV9 can readily transduce MNs and astrocytes in non-human primates.(8,34,35) Thus, as new potential therapeutic targets emerge for sporadic ALS, AAV9 could be utilized as an efficient tool to manipulate these cell types.”
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Focused shockwave induced blood-brain barrier opening and transfection
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mCerulean3-Based Cameleon Sensor to Explore Mitochondrial Ca2+ Dynamics In Vivo
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Brain endothelial specific gene therapy improves experimental Sandhoff disease
Dogbevia, G., Graßhoff, H., Othman, A., Penno, A., & Schwaninger, M. (2019) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x19865917 · Cited by 34
“Indeed, vectors based on AAV serotype 9 cross the blood–brain barrier to some extent.(7) A high dose of AAV9 vector administered to Hexb / mice ameliorated the neurological deficit and prolonged survival but also triggered liver and lung tumors in many mice.”
BackgroundDosage-sensitive genes in autism spectrum disorders: From neurobiology to therapy
Javed, S., Selliah, T., Lee, Y., & Huang, W. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.08.009 · Cited by 32
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New and developing therapies in spinal muscular atrophy
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Optogenetic Approaches for Controlling Seizure Activity
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“Methods to improve viral spread such as delivery to the cerebrospinal fluid [98,99], convectionenhanced delivery [100,101], or utilizing particular viral serotypes [102–104] would allow larger structures to be targeted.”
BackgroundEfficacy of a Bicistronic Vector for Correction of Sandhoff Disease in a Mouse Model
Woodley, E., Osmon, K. J. L., Thompson, P., Richmond, C. R., Chen, Z., Gray, S. J., & Walia, J. S. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.10.011 · Cited by 32
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Hocquemiller, M., Hemsley, K. M., Douglass, M. L., Tamang, S. J., Neumann, D., King, B. M., Beard, H., Trim, P. J., Winner, L. K., Lau, A. A., et al. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.12.001 · Cited by 33
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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