The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
Global CNS gene delivery and evasion of anti-AAV-neutralizing antibodies by intrathecal AAV administration in non-human primates
Open accessAbstract
Injection of adeno-associated virus (AAV) into the cerebrospinal fluid (CSF) offers a means to achieve widespread transgene delivery to the central nervous system, where the doses can be readily translated from small to large animals. In contrast to studies with other serotypes (AAV2, AAV4 and AAV5) in rodents, we report that a naturally occurring capsid (AAV9) and rationally engineered capsid (AAV2.5) are able to achieve broad transduction throughout the brain and spinal cord parenchyma following a single injection into the CSF (via cisterna magna or lumbar cistern) in non-human primates (NHP). Using either vector at a dose of ∼2 × 10(12) vector genome (vg) per 3-6 kg animal, approximately 2% of the entire brain and spinal cord was transduced, covering all regions of the central nervous system (CNS). AAV9 in particular displayed efficient transduction of spinal cord motor neurons. The peripheral organ biodistribution was highly reduced compared with intravascular delivery, and the presence of circulating anti-AAV-neutralizing antibodies up to a 1:128 titer had no inhibitory effect on CNS gene transfer. Intra-CSF delivery effectively translates from rodents to NHPs, which provides encouragement for the use of this approach in humans to treat motor neuron and lysosomal storage diseases.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The circulation of CSF delivers viral vectors to broader CNS regions when compared to IP injection [86].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [86]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“in animal models, widespread coverage can be obtained by delivering the vector into the CSF”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
Intrathecal morphine in mice: A new technique
Hylden, J. L. K., & Wilcox, G. L. (1980) · European Journal of Pharmacology · doi:10.1016/0014-2999(80)90515-4 · Cited by 1,930
Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2009) · Nature Biotechnology · doi:10.1038/nbt.1515 · Cited by 1,456 · cited 1×
“Recently, the adeno-associated virus (AAV) serotype 9 capsid was identified as a vector capable of transducing neurons and glia throughout the CNS following intravenous delivery in adult rodents, cats, and NHPs [1-5].”
BackgroundXiao, X., Li, J., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2224-2232.1998 · Cited by 1,381
Boutin, S., Monteilhet, V., Veron, P., Leborgne, C., Benveniste, O., Montus, M. F., & Masurier, C. (2010) · Human Gene Therapy · doi:10.1089/hum.2009.182 · Cited by 970
McCarty, D., Monahan, P., & Samulski, R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301514 · Cited by 735
Self-citationProduction and characterization of adeno-associated viral vectors
Grieger, J. C., Choi, V. W., & Samulski, R. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.207 · Cited by 580
McCarty, D. M., Fu, H., Monahan, P. E., Toulson, C. E., Naik, P., & Samulski, R. J. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302134 · Cited by 547
Self-citationDavidson, B. L., Stein, C. S., Heth, J. A., Martins, I., Kotin, R. M., Derksen, T. A., Zabner, J., Ghodsi, A., & Chiorini, J. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3428 · Cited by 531
Duque, S., Joussemet, B., Riviere, C., Marais, T., Dubreil, L., Douar, A.-M., Fyfe, J., Moullier, P., Colle, M.-A., & Barkats, M. (2009) · Molecular Therapy · doi:10.1038/mt.2009.71 · Cited by 511
Gray, S. J., Matagne, V., Bachaboina, L., Yadav, S., Ojeda, S. R., & Samulski, R. J. (2011) · Molecular Therapy · doi:10.1038/mt.2011.72 · Cited by 501
Self-citationGray, S. J., Foti, S. B., Schwartz, J. W., Bachaboina, L., Taylor-Blake, B., Coleman, J., Ehlers, M. D., Zylka, M. J., McCown, T. J., & Samulski, R. J. (2011) · Human Gene Therapy · doi:10.1089/hum.2010.245 · Cited by 420
Self-citationPhase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector
Bowles, D. E., McPhee, S. W., Li, C., Gray, S. J., Samulski, J. J., Camp, A. S., Li, J., Wang, B., Monahan, P. E., Rabinowitz, J. E., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2011.237 · Cited by 400
Self-citationDrug transport in brain via the cerebrospinal fluid.
Pardridge, W. M. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-7 · Cited by 316
Peptide Drug Delivery to the Brain
(1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-116-9-783_2 · Cited by 311
Adeno-Associated Virus Serotype 9 Transduction in the Central Nervous System of Nonhuman Primates
Samaranch, L., Salegio, E. A., San Sebastian, W., Kells, A. P., Foust, K. D., Bringas, J. R., Lamarre, C., Forsayeth, J., Kaspar, B. K., & Bankiewicz, K. S. (2012) · Human Gene Therapy · doi:10.1089/hum.2011.200 · Cited by 299
Swindle, M. M. (2007) · CRC Press eBooks · doi:10.1201/9781420009156 · Cited by 239
Gray, S. J., Blake, B. L., Criswell, H. E., Nicolson, S. C., Samulski, R. J., & McCown, T. J. (2010) · Molecular Therapy · doi:10.1038/mt.2009.292 · Cited by 185
Self-citationRobust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs
Federici, T., Taub, J. S., Baum, G. R., Gray, S. J., Grieger, J. C., Matthews, K. A., Handy, C. R., Passini, M. A., Samulski, R. J., & Boulis, N. M. (2011) · Gene Therapy · doi:10.1038/gt.2011.130 · Cited by 169
Self-citationComparison of Adeno-Associated Viral Vector Serotypes for Spinal Cord and Motor Neuron Gene Delivery
Snyder, B. R., Gray, S. J., Quach, E. T., Huang, J. W., Leung, C. H., Samulski, R. J., Boulis, N. M., & Federici, T. (2011) · Human Gene Therapy · doi:10.1089/hum.2011.008 · Cited by 156
Self-citationTowne, C. L., Pertin, M., Beggah, A., Aebischer, P., & Décosterd, I. (2009) · Molecular Pain · doi:10.1186/1744-8069-5-52 · Cited by 148
Sensory neuron targeting by self-complementary AAV8 via lumbar puncture for chronic pain
Storek, B., Reinhardt, M., Wang, C., Janssen, W. G. M., Harder, N. M., Banck, M. S., Morrison, J. H., & Beutler, A. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708003105 · Cited by 123
Vulchanova, L., Schuster, D. J., Belur, L. R., Riedl, M. S., Podetz-Pedersen, K. M., Kitto, K. F., Wilcox, G. L., McIvor, R. S., & Fairbanks, C. A. (2010) · Molecular Pain · doi:10.1186/1744-8069-6-31 · Cited by 115
Liu, G., Martins, I. H., Chiorini, J. A., & Davidson, B. L. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302554 · Cited by 84
Ghodsi, A., Stein, C. S., Derksen, T. A., Martins, I., Anderson, R. D., & Davidson, B. L. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7205 · Cited by 77
Sowa, N. A., Street, S. E., Vihko, P., & Zylka, M. J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2162-10.2010 · Cited by 69
Storek, B., Harder, N. M., Banck, M. S., Wang, C., McCarty, D. M., Janssen, W. G. M., Morrison, J. H., Walsh, C., & Beutler, A. S. (2006) · Molecular Pain · doi:10.1186/1744-8069-2-4 · Cited by 54
Morgan, C. J., Pyne‐Geithman, G. J., Jauch, E. C., Shukla, R., Wagner, K. R., Clark, J. F., & Zuccarello, M. (2004) · Journal of neurosurgery · doi:10.3171/jns.2004.101.6.1026 · Cited by 23
Kao, J., Chen, S., Ma, H. I., Law, P., Tao, P., & Loh, H. H. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.165399 · Cited by 21
Flagged first, then by citations
1 of the 30 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Snyder BR, Gray SJ, Quach ET, Huang JW, Leung CH, Samulski RJ et al. Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery. Hum Gene Ther 2011; 22: 1129–1135. · DOI
Cited by
Sorted by citations
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
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
Strategies for delivering therapeutics across the blood–brain barrier
Terstappen, G. C., Meyer, A. H., Bell, R. D., & Zhang, W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00139-y · Cited by 1,138
Hinderer, C., Katz, N., Buza, E. L., Dyer, C., Goode, T., Bell, P., Richman, L. K., & Wilson, J. M. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.015 · Cited by 814
“34,35 The lesions observed in the present study consisted of degeneration of DRG sensory neuron cell bodies as well as their central and peripheral axons.”
Current clinical applications of in vivo gene therapy with AAVs
Mendell, J. R., Al-Zaidy, S. A., Rodino-Klapac, L. R., Goodspeed, K., Gray, S. J., Kay, C. N., Boye, S. L., Boye, S. E., George, L. A., Salabarria, S., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2020.12.007 · Cited by 743
Self-citation
Metadata
- Authors
- Gray, S. J., Nagabhushan Kalburgi, S., McCown, T. J., & Jude Samulski, R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Gene Therapy
- Published
- 2013-01-10
- Volume
- 20
- Issue
- 4
- Pages
- 450-459
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC3618620
- OpenAlex
- W2092757238
- Cited by
- 377
- References
- 30
- Citations by year
- 2026: 17 · 2025: 37 · 2024: 31 · 2023: 30 · 2022: 30 · 2021: 43 · 2020: 32 · 2019: 19 · 2018: 27 · 2017: 16 · 2016: 21 · 2015: 23 · 2014: 37 · 2013: 14
- FWCI
- 20.99
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-04-04)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (5u54ar056953-05)
- National Institute of Allergy and Infectious Diseases (R01AI072176)
- National Institute of Neurological Disorders and Stroke (NS 35633, R43NS063611, R01NS035633)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54-AR056953)
- National Center for Research Resources (UL1RR025747)
- 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
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Keywords
- adeno-associated virus, AAV9, intrathecal gene delivery, cerebrospinal fluid injection, antibody escape, spinal cord, non-human primates, lysosomal storage disease, motor neuron disease, vector biodistribution
- MeSH terms
- Dependovirus, Animals, Blood Vessels, Brain, Genetic Vectors, Injections, Spinal, Macaca fascicularis, Mice, Inbred BALB C, Motor Neurons, Spinal Cord, Tissue Distribution, Transduction, Genetic, Rats, Sprague-Dawley, Mice, Rats, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
