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Differential Transd...
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Dodiya, Hemraj B.
(author)
Differential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates
- Article/chapterEnglish2010
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LIBRIS-ID:oai:lup.lub.lu.se:b35e2f3c-921c-4f40-8472-5a2d2f272175
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https://lup.lub.lu.se/record/1588247URI
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https://doi.org/10.1038/mt.2009.216DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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We examined the transduction efficiency of different adeno-associated virus (AAV) capsid serotypes encoding for green fluorescent protein (GFP) flanked by AAV2 inverted terminal repeats in the nonhuman primate basal ganglia as a prelude to translational studies, as well as clinical trials in patients with Parkinson's disease (PD). Six intact young adult cynomolgus monkeys received a single 10 mu l injection of AAV2/1-GFP, AAV2/5-GFP, or AAV2/8-GFP pseudotyped vectors into the caudate nucleus and putamen bilaterally in a pattern that resulted in each capsid serotype being injected into at least four striatal sites. GFP immunohistochemistry revealed excellent transduction rates for each AAV pseudotype. Stereological estimates of GFP(+) cells within the striatum revealed that AAV2/5-GFP transduces significantly higher number of cells than AAV2/8-GFP (P < 0.05) and there was no significant difference between AAV2/5-GFP and AAV2/1-GFP (P = 0.348). Consistent with this result, Cavalieri estimates revealed that AAV2/5-GFP resulted in a significantly larger transduction volume than AAV2/8-GFP (P < 0.05). Each pseudotype transduced striatal neurons effectively [>95% GFP(+) cells colocalized neuron-specific nuclear protein (NeuN)]. The current data suggest that AAV2/5 and AAV2/1 are superior to AAV2/8 for gene delivery to the nonhuman primate striatum and therefore better candidates for therapeutic applications targeting this structure.
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Björklund, TomasLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Molekylär neuromodulering,Lund University Research Groups,Molecular Neuromodulation(Swepub:lu)mphy-tbj
(author)
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Stansell, James, III
(author)
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Mandel, Ronald J.
(author)
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Kirik, DenizLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-dki
(author)
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Kordower, Jeffrey H.
(author)
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Brain Repair and Imaging in Neural Systems (BRAINS)Forskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
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In:Molecular Therapy: Elsevier BV18:3, s. 579-5871525-00241525-0016
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