Enhanced Gene Transfer Efficiency in the Murine Striatum and an Orthotopic Glioblastoma Tumor Model, Using AAV-7- and AAV-8-Pseudotyped Vectors

Harding, Thomas C.; Dickinson, Peter J.; Roberts, Byron N.; Yendluri, Satya; Gonzalez-Edick, Melissa; Lecouteur, Richard A.; Jooss, Karin U.

doi:10.1089/hum.2006.17.807

Cited by 45Virus-based gene therapy researchRNA Interference and Gene DeliveryBarrier Structure and Function Studies

Enhanced Gene Transfer Efficiency in the Murine Striatum and an Orthotopic Glioblastoma Tumor Model, Using AAV-7- and AAV-8-Pseudotyped Vectors

Harding, Thomas C., Dickinson, Peter J., Roberts, Byron N., Yendluri, Satya, Gonzalez-Edick, Melissa, Lecouteur, Richard A., Jooss, Karin U.·2006·Human Gene Therapy

DOI 10.1089/hum.2006.17.807

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Abstract

In this study, recombinant AAV vectors pseudotyped with viral capsids derived from AAV serotypes 7 and 8 were evaluated for gene transfer in the murine striatum relative to vectors pseudotyped with AAV serotypes 2, 5, and 6. In comparison with rAAV serotype 2, pseudotyped vectors derived from AAV-7 and AAV-8 have increased transduction efficiency in the murine CNS, with the rank order rAAV-7 > rAAV-8 > rAAV-5 > rAAV-2 = rAAV-6, with all vectors demonstrating a marked tropism for neuronal transduction. Pseudotyped rAAV vector gene transfer in the brain after preimplantation of a murine 4C8 glioblastoma tumor was also evaluated. Efficiency of gene transfer to the orthotopic tumor was increased when using AAV-6, -7, and -8 capsid proteins in comparison with serotype 2, with the order rAAV-8 = rAAV-7 > rAAV-6 > rAAV-2 > rAAV-5. The increased gene transfer efficiency of rAAV vectors pseudotyped with the rAAV-8 capsid also provided enhanced therapeutic efficacy in a mouse model of glioblastoma multiforme, using vectors encoding an inhibitor of the vascular endothelial growth factor pathway. These studies demonstrate that rAAV vectors pseudotyped with capsids derived from AAV serotypes 7 and 8 provide enhanced gene transfer in the murine CNS and may offer increased therapeutic efficacy in the treatment of neurological disease.

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AAV8 and AAV9 exhibit a dominant neuronal tropism after direct injection into the rodent striatum as well as in other brain structures.
“AAV8 and AAV9 exhibit a dominant neuronal tropism after direct injection into the rodent striatum9,13,16,27 as well as in other brain structures.12,28,29”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [9]

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Authors: Harding, T. C., Dickinson, P. J., Roberts, B. N., Yendluri, S., Gonzalez-Edick, M., Lecouteur, R. A., & Jooss, K. U.
Affiliations: Genesys (United States) (US)
University of California, Davis (US)
Cell Genesys, South San Francisco, CA 94080.
ORCID: Dickinson, Peter J.
Lecouteur, Richard A.
Jooss, Karin U.
Venue: Human Gene Therapy
Publisher: SAGE Publications
Published: 2006-08
Volume: 17
Issue: 8
Pages: 807-820
ISSN: 1043-0342 (ISSN-L)
1557-7422
DOI: 10.1089/hum.2006.17.807
OpenAlex: W2025830548
Cited by: 45
References: 75
Citations by year: 2025: 1 · 2024: 2 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 4
FWCI: 2.65
Type: journal article
Language: en
Open access: closed
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Human Gene Therapy (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: recombinant adeno-associated virus, gene transfer efficiency, striatum, neuronal transduction, glioblastoma
MeSH terms: Dependovirus, Animals, Brain Neoplasms, Capsid, Corpus Striatum, Genetic Vectors, Glioblastoma, Humans, Mice, Transgenic, Neoplasm Transplantation, Neoplasms, Experimental, Species Specificity, Transduction, Genetic, Genetic Therapy, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Mice

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Enhanced Gene Transfer Efficiency in the Murine Striatum and an Orthotopic Glioblastoma Tumor Model, Using AAV-7- and AAV-8-Pseudotyped Vectors

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