Differential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates
(2010) In Molecular Therapy 18(3). p.579-587- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1588247
- author
- Dodiya, Hemraj B. ; Björklund, Tomas LU ; Stansell, James, III ; Mandel, Ronald J. ; Kirik, Deniz LU and Kordower, Jeffrey H.
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Therapy
- volume
- 18
- issue
- 3
- pages
- 579 - 587
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000275454500017
- scopus:77649270699
- pmid:19773746
- ISSN
- 1525-0024
- DOI
- 10.1038/mt.2009.216
- language
- English
- LU publication?
- yes
- id
- b35e2f3c-921c-4f40-8472-5a2d2f272175 (old id 1588247)
- date added to LUP
- 2016-04-01 10:07:51
- date last changed
- 2022-05-17 20:03:28
@article{b35e2f3c-921c-4f40-8472-5a2d2f272175, abstract = {{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.}}, author = {{Dodiya, Hemraj B. and Björklund, Tomas and Stansell, James, III and Mandel, Ronald J. and Kirik, Deniz and Kordower, Jeffrey H.}}, issn = {{1525-0024}}, language = {{eng}}, number = {{3}}, pages = {{579--587}}, publisher = {{Nature Publishing Group}}, series = {{Molecular Therapy}}, title = {{Differential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates}}, url = {{http://dx.doi.org/10.1038/mt.2009.216}}, doi = {{10.1038/mt.2009.216}}, volume = {{18}}, year = {{2010}}, }