Controlled dissemination of AAV vectors in the primate brain
Abstract
Adeno-associated viral (AAV) vectors are currently the preeminent gene therapy vehicles for neurological application. However, issues regarding the trafficking of AAV vectors within the primate brain, and consequently control over the targeting of transgene expression, remain a matter of investigation. Studies in nonhuman primates have shown that distribution of AAV vectors is largely mediated by the flow of cerebrospinal fluid within perivascular space, trafficking of vector along axonal projections, and AAV receptor binding. Together these processes can result in transduction of cells in areas distant from the parenchymal site of infusion. Additionally, we have addressed the unique surgical issues concerning delivery of AAV vectors by convection-enhanced delivery and are working toward tailored delivery by means of real-time MRI.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Convection-enhanced delivery increases the vector volume that can be delivered to the target site and enhances cell transduction in the targeted CNS substructure.
“This has the advantage of increased vector volume that can be delivered to the target site, which enhances cell transduction in the targeted CNS substructure”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [80]
Cites
Convection-enhanced delivery of macromolecules in the brain.
Bobo, R. H., Laske, D. W., Akbaşak, A., Morrison, P. F., Dedrick, R. L., & Oldfield, E. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.6.2076 · Cited by 1,414 · see citing works
Summerford, C., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.2.1438-1445.1998 · Cited by 1,409 · see citing works
Rennels, M. L., Gregory, T. F., Blaumanis, O. R., Fujimoto, K., & Grady, P. A. (1985) · Brain Research · doi:10.1016/0006-8993(85)91383-6 · Cited by 752 · see citing works
Bankiewicz, K. S., Eberling, J. L., Kohutnicka, M., Jagust, W. J., Pivirotto, P., Bringas, J., Cunningham, J., Budinger, T. F., & Harvey-White, J. D. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7408 · Cited by 406 · see citing works
Self-citationResults from a phase I safety trial of <i>hAADC</i> gene therapy for Parkinson disease
Eberling, J. L., Jagust, W. J., Christine, C. W., Starr, P., Larson, P., Bankiewicz, K. S., & Aminoff, M. J. (2008) · Neurology · doi:10.1212/01.wnl.0000312381.29287.ff · Cited by 370 · see citing works
Self-citationWu, Z., Miller, E. B., Agbandje‐McKenna, M., & Samulski, R. J. (2006) · Journal of Virology · doi:10.1128/jvi.00895-06 · Cited by 327 · see citing works
Immune Responses to AAV in Clinical Trials
Mingozzi, F., & A. High, K. (2011) · Current Gene Therapy · doi:10.2174/156652311796150354 · Cited by 324 · see citing works
Massion, J. (1967) · Physiological Reviews · doi:10.1152/physrev.1967.47.3.383 · Cited by 322 · see citing works
Hadaczek, P., Yamashita, Y., Mirek, H., Tamas, L. B., Bohn, M. C., Noble, C. O., Park, J. W., & Bankiewicz, K. S. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.02.018 · Cited by 312 · see citing works
Self-citationImmune Responses to AAV in Clinical Trials
Mingozzi, F., & High, K. A. (2007) · Current Gene Therapy · doi:10.2174/156652307782151425 · Cited by 238 · see citing works
Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents
Krauze, M. T., Saito, R., Noble, C. O., Tamas, M., Bringas, J., Park, J. W., Berger, M. S., & Bankiewicz, K. S. (2005) · Journal of neurosurgery · doi:10.3171/jns.2005.103.5.0923 · Cited by 235 · see citing works
Self-citationCearley, C. N., & Wolfe, J. H. N. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2185-07.2007 · Cited by 212 · see citing works
Rapid solute transport throughout the brain via paravascular fluid pathways.
Rennels, M. L., Blaumanis, O. R., & Grady, P. A. (1990) · PubMed · Cited by 204 · see citing works
Slevin, J. T., Gash, D. M., Smith, C. D., Gerhardt, G. A., Kryscio, R., Chebrolu, H., Walton, A., Wagner, R., & Young, A. B. (2007) · Journal of neurosurgery · doi:10.3171/jns.2007.106.4.614 · Cited by 173 · see citing works
Kunwar, S. (2003) · Springer eBooks · doi:10.1007/978-3-7091-6090-9_16 · Cited by 158 · see citing works
Hamilton, J. F., Morrison, P. F., Chen, M. Y., Harvey-White, J. D., Sánchez‐Pernaute, R., PHILLIPS, H. S., Oldfield, E. H., & Bankiewicz, K. S. (2001) · Experimental Neurology · doi:10.1006/exnr.2000.7571 · Cited by 157 · see citing works
Self-citationTargeted Retrograde Gene Delivery for Neuronal Protection
Kaspar, B. K., Erickson, D. A., Schaffer, D. V., Hinh, L., Gage, F. H., & Peterson, D. A. (2002) · Molecular Therapy · doi:10.1006/mthe.2001.0520 · Cited by 147 · see citing works
Jacobson, S. G., Boye, S. L., Alemán, T. S., Conlon, T. J., Zeiss, C. J., Román, A. J., Cideciyan, A. V., Schwartz, S., Komáromy, A. M., Doobrajh, M., et al. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.845 · Cited by 145 · see citing works
Image-Guided Convection-Enhanced Delivery Platform in the Treatment of Neurological Diseases
Fiandaca, M. S., Forsayeth, J., Dickinson, P. J., & Bankiewicz, K. S. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2007.10.064 · Cited by 140 · see citing works
Self-citationNguyen, J. B., Sánchez‐Pernaute, R., Cunningham, J., & Bankiewicz, K. S. (2001) · Neuroreport · doi:10.1097/00001756-200107030-00037 · Cited by 135 · see citing works
Self-citationEfficient gene therapy-based method for the delivery of therapeutics to primate cortex
Kells, A. P., Hadaczek, P., Yin, D., Bringas, J., Varenika, V., Forsayeth, J., & Bankiewicz, K. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810682106 · Cited by 134 · see citing works
Self-citationReal-time MR imaging of adeno-associated viral vector delivery to the primate brain
Fiandaca, M. S., Varenika, V., Eberling, J. L., McKnight, T. R., Bringas, J., Pivirotto, P., Beyer, J., Hadaczek, P., Bowers, W. J., Park, J. B., et al. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.11.012 · Cited by 122 · see citing works
Self-citationDetection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery
Varenika, V., Dickinson, P. J., Bringas, J., LeCouteur, R. A., Higgins, R., Park, J. B., Fiandaca, M. S., Berger, M. S., Sampson, J. H., & Bankiewicz, K. S. (2008) · Journal of neurosurgery · doi:10.3171/jns/2008/109/11/0874 · Cited by 110 · see citing works
Self-citationA Dose-Ranging Study of AAV-hAADC Therapy in Parkinsonian Monkeys
Forsayeth, J., Eberling, J. L., Sanftner, L. M., Zhen, Z., Pivirotto, P., Bringas, J., Cunningham, J., & Bankiewicz, K. S. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.04.008 · Cited by 103 · see citing works
Self-citationDickinson, P. J., LeCouteur, R. A., Higgins, R. J., Bringas, J. R., Roberts, B., Larson, R. F., Yamashita, Y., Krauze, M. T., Noble, C. O., Drummond, D. C., et al. (2008) · Journal of neurosurgery · doi:10.3171/jns/2008/108/5/0989 · Cited by 94 · see citing works
Self-citationKrauze, M. T., McKnight, T. R., Yamashita, Y., Bringas, J., Noble, C. O., Saito, R., Geletneky, K., Forsayeth, J., Berger, M. S., Jackson, P., et al. (2005) · Brain Research Protocols · doi:10.1016/j.brainresprot.2005.08.003 · Cited by 93 · see citing works
Self-citationHadaczek, P., Forsayeth, J., Mirek, H., Munson, K., Bringas, J., Pivirotto, P., L McBride, J., Davidson, B. L., & Bankiewicz, K. S. (2009) · Human Gene Therapy · doi:10.1089/hum.2008.151 · Cited by 90 · see citing works
Self-citationStriatal Delivery of rAAV-hAADC to Rats with Preexisting Immunity to AAV
Sanftner, L. M., Suzuki, B. M., Doroudchi, M. M., Feng, L., McClelland, A., Forsayeth, J. R., & Cunningham, J. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2003.12.005 · Cited by 89 · see citing works
Self-citationMastakov, M. Y., Baer, K., Kotin, R. M., & During, M. J. (2002) · Molecular Therapy · doi:10.1006/mthe.2002.0564 · Cited by 85 · see citing works
Massion, J. (1988) · Behavioural Brain Research · doi:10.1016/0166-4328(88)90071-x · Cited by 75 · see citing works
Herzog, C. D., Dass, B., Gasmi, M., Bakay, R., Stansell, J. E., Tuszynski, M., Bankiewicz, K., Chen, E.-Y., Chu, Y., Bishop, K., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.170 · Cited by 72 · see citing works
Self-citationCunningham, J., Pivirotto, P., Bringas, J., Suzuki, B. M., Vijay, S., Sanftner, L. M., Kitamura, M., Chan, C. M., & Bankiewicz, K. S. (2008) · Molecular Therapy · doi:10.1038/mt.2008.111 · Cited by 68 · see citing works
Self-citationCurrent status of gene therapy trials for Parkinson's disease
Fiandaca, M. S., Forsayeth, J., & Bankiewicz, K. S. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.08.009 · Cited by 60 · see citing works
Self-citationHackett, N. R., Redmond, D. E., Sondhi, D., Giannaris, E. L., Vassallo, E., Stratton, J., Qiu, J., Kaminsky, S. M., Lesser, M. L., Fisch, G. S., et al. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.1484 · Cited by 57 · see citing works
Hadaczek, P., Mirek, H., Bringas, J., Cunningham, J., & Bankiewicz, K. S. (2004) · Human Gene Therapy · doi:10.1089/10430340460745793 · Cited by 54 · see citing works
Self-citationKrauze, M. T., VandenBerg, S. R., Yamashita, Y., Saito, R., Forsayeth, J., Noble, C. O., Park, J. B., & Bankiewicz, K. S. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.12.015 · Cited by 51 · see citing works
Self-citationFoust, K. D., Flotte, T. R., Reier, P. J., & Mandel, R. J. (2007) · Human Gene Therapy · doi:10.1089/hum.2007.104 · Cited by 37 · see citing works
Gene therapy of the central nervous system : from bench to bedside
Kaplitt, M. G., & During, M. J. (2006) · Cited by 34 · see citing works
ANATOMIC COMPRESSION CAUSED BY HIGH-VOLUME CONVECTION-ENHANCED DELIVERY TO THE BRAIN
Valles, F. E., Fiandaca, M. S., Bringas, J., Dickinson, P. J., LeCouteur, R. A., Higgins, R., Berger, M. S., Forsayeth, J., & Bankiewicz, K. S. (2009) · Neurosurgery · doi:10.1227/01.neu.0000350229.77462.2f · Cited by 34 · see citing works
Self-citationLevy, R. M. (2001) · Journal of NeuroVirology · doi:10.1080/13550280152537283 · Cited by 30 · see citing works
Red nucleus: role in motor control
Houk, J. (1991) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(05)80037-6 · Cited by 29 · see citing works
Influence of the Immune System on Central Nervous System Gene Transfer
Forsayeth, J. (2006) · Elsevier eBooks · doi:10.1016/b978-012397632-1/50005-8 · Cited by 5 · see citing works
Self-citationKordower (1999) · doi:10.1002/1531-8249(199909)46:3
Flagged first, then by citations
2 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
State-of-the-art gene-based therapies: the road ahead
Kay, M. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2971 · Cited by 672 · see citing works
Aβ-degrading enzymes: potential for treatment of Alzheimer disease
Miners, J. S., Barua, N., Kehoe, P. G., Gill, S., & Love, S. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182345e46 · Cited by 265 · see citing works
Gene Therapy for Neurodegenerative Diseases
Sudhakar, V., & Richardson, R. M. (2019) · Neurotherapeutics · doi:10.1007/s13311-018-00694-0 · Cited by 212 · see citing works
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 169 · see citing works
Adeno-associated virus (AAV) gene therapy for neurological disease
Weinberg, M. S., Samulski, R. J., & McCown, T. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.03.004 · Cited by 154 · see citing works
Kells, A. P., Eberling, J. L., Su, X., Pivirotto, P., Bringas, J., Hadaczek, P., Narrow, W. C., Bowers, W. J., Federoff, H. J., Forsayeth, J., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0942-10.2010 · Cited by 133 · see citing works
Self-citationBarua, N. U., Gill, S. S., & Love, S. (2013) · Brain Pathology · doi:10.1111/bpa.12082 · Cited by 127 · see citing works
An Open Resource for Non-human Primate Optogenetics
Tremblay, S., Acker, L., Afraz, A., Albaugh, D. L., Amita, H., Andrei, A. R., Angelucci, A., Aschner, A., Balan, P. F., Basso, M. A., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.027 · Cited by 112 · see citing works
Primate optogenetics: Progress and prognosis
El-Shamayleh, Y., & Horwitz, G. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902284116 · Cited by 73 · see citing works
Parambi, D. G. T., Alharbi, K. S., Kumar, R., Harilal, S., Batiha, G. E., Martins, N. A., Hendawy, O. M., Musa, A., Panda, D. S., & Mathew, B. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02555-y · Cited by 75 · 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
Convection-enhanced delivery of M13 bacteriophage to the brain
Ksendzovsky, A., Walbridge, S., Saunders, R. C., Asthagiri, A. R., Heiss, J. D., & Lonser, R. R. (2012) · Journal of neurosurgery · doi:10.3171/2012.4.jns111528 · Cited by 64 · see citing works
Extensive Transduction and Enhanced Spread of a Modified AAV2 Capsid in the Non-human Primate CNS
Naidoo, J., Stanek, L. M., Ohno, K., Trewman, S., Samaranch, L., Hadaczek, P., O’Riordan, C. R., Sullivan, J., Sebastián, W. S., Bringas, J. R., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.07.008 · Cited by 59 · see citing works
Self-citationLim, D. A., Potts, M., & Silvestrini, M. T. (2013) · Surgical Neurology International · doi:10.4103/2152-7806.109190 · Cited by 56 · see citing works
AAV viral vector delivery to the brain by shape-conforming MR-guided infusions
Bankiewicz, K. S., Sudhakar, V. R., Samaranch, L., Sebastián, W. S., Bringas, J., & Forsayeth, J. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.034 · Cited by 52 · see citing works
Self-citationSan Sebastian, W., Richardson, R. M., Kells, A. P., Lamarre, C., Bringas, J., Pivirotto, P., Salegio, E. A., DeArmond, S. J., Forsayeth, J., & Bankiewicz, K. S. (2012) · Human Gene Therapy · doi:10.1089/hum.2011.162 · Cited by 48 · see citing works
Self-citationSalegio, E. A., Streeter, H., Dube, N., Hadaczek, P., Samaranch, L., Kells, A. P., Sebastián, W. S., Zhai, Y., Bringas, J., Xu, T., et al. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00009 · Cited by 48 · see citing works
Self-citationSalegio, E. A., Kells, A. P., Richardson, R. M., Hadaczek, P., Forsayeth, J., Bringas, J., Sardi, S. P., Passini, M. A., Shihabuddin, L. S., Cheng, S. H., et al. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.040 · Cited by 42 · see citing works
Self-citationWu, Y., Jiang, L., Geng, H., Yang, T., Han, Z., He, X.-B., Lin, K., & Xu, F. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.05.005 · Cited by 39 · see citing works
Guided delivery of adeno-associated viral vectors into the primate brain
Salegio, E. A., Samaranch, L., Kells, A. P., Forsayeth, J., & Bankiewicz, K. S. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.10.005 · Cited by 35 · see citing works
Self-citationNonaka, M., Kim, R., Sharry, S., Matsushima, A., Takemoto‐Kimura, S., & Bito, H. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.08.010 · Cited by 29 · see citing works
Gene Therapy in Mouse Models of Huntington Disease
Southwell, A. L., & Patterson, P. H. (2011) · The Neuroscientist · doi:10.1177/1073858410386236 · Cited by 20 · see citing works
Dopaminergic Cell Replacement for Parkinson’s Disease: Addressing the Intracranial Delivery Hurdle
Maheshwari, S., Akram, H., Bulstrode, H. J. C. J., Kalia, S. K., Morizane, A., Takahashi, J. B., & Natalwala, A. (2024) · Journal of Parkinson s Disease · doi:10.3233/jpd-230328 · Cited by 13 · see citing works
Miranpuri, G. S., Kumbier, L., Hinchman, A., Schomberg, D. T., Wang, A., Marshall, H., Kubota, K., Ross, C., & Sillay, K. A. (2012) · Annals of Neurosciences · doi:10.5214/ans.0972.7531.190310 · Cited by 12 · see citing works
Optogenetics in primate cortical networks
Merlin, S., & Vidyasagar, T. R. (2023) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2023.1193949 · Cited by 7 · see citing works
Gene Therapy for Parkinson's Disease
Sudhakar, V. R., & Richardson, R. M. (2018) · Progress in neurological surgery · doi:10.1159/000481109 · Cited by 5 · see citing works
Boroujeni, K. B., Balaram, P., Tiesinga, P. H. E., & Womelsdorf, T. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102873 · Cited by 4 · see citing works
Biotherapies for Parkinson disease
Rémy, P. (2014) · Revue Neurologique · doi:10.1016/j.neurol.2014.10.002 · Cited by 3 · see citing works
Synthetic serum markers enable noninvasive monitoring of gene expression in primate brains
Lee, S., Romac, M. D., Watanabe, S., Chernov, M. M., Li, H., Raisley, E. K., Rothenhoefer, K. M., Dahlquist, Z., Szablowski, J. O., & Costa, V. D. (2026) · Neuron · doi:10.1016/j.neuron.2026.01.003 · Cited by 2 · see citing works
GDNF and AADC Gene Therapy for Parkinson’s Disease
Bankiewicz, K. S., Sebastián, W. S., Samaranch, L., & Forsayeth, J. (2016) · Springer eBooks · doi:10.1007/978-1-4899-7654-3_4 · Cited by 2 · see citing works
Self-citationDirect Convective Nervous System Drug Delivery for Patients with Neurodegenerative Disorders
Richardson, R. M., & Larson, P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813997-4.00023-2 · Cited by 2 · see citing works
Editorial: Convection-enhanced delivery
Elder, J. B., & Chiocca, E. A. (2012) · Journal of neurosurgery · doi:10.3171/2012.1.jns112262 · Cited by 2 · see citing works
Myokardialer Gentransfer mittels Adenoassoziierter Viraler Vektoren
Steinbeck, G. (2012)
- Authors
- Varenika, V., Kells, A. P., Valles, F., Hadaczek, P., Forsayeth, J., & Bankiewicz, K. S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Bankiewicz, Krystof S.
- Venue
- Progress in Brain Research
- Publisher
- Elsevier
- Published
- 2009
- Volume
- 175
- Pages
- 163-172
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W1500887617
- Cited by
- 33
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 5 · 2016: 2 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 6.06
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- 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
- adeno-associated virus vectors, gene therapy vectors, primate brain, cerebrospinal fluid flow, perivascular spaces, axonal transport, convection-enhanced delivery, surgical delivery, real-time MRI guidance, non-human primates
- MeSH terms
- Adenoviridae, Animals, Brain, Genetic Vectors, Humans, Primates, Transduction, Genetic, Genetic Therapy
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
