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@article{1827942,
author = {Pietersz, KL and Pouw, S and Klima, J and Ellederova, Z and Bohuslavova, B and Chrastina, Jan and Liscak, R and Urgosik, D and Starek, Z and Crha, M and Lewis, O and Wooley, M and Johnson, D and Brouwers, CC and Evers, M and Motlik, J and Martens, GJM and Konstantinova, PS and Blits, B},
article_location = {AMSTERDAM},
doi = {http://dx.doi.org/10.1016/j.jneumeth.2021.109382},
keywords = {AAV; CED; Minipigs; CNS},
language = {eng},
issn = {0165-0270},
journal = {Journal of Neuroscience Methods},
note = {Bez afiliace k MU.},
title = {Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas},
volume = {365},
year = {2022}
}
TY - JOUR
ID - 1827942
AU - Pietersz, KL - Pouw, S - Klima, J - Ellederova, Z - Bohuslavova, B - Chrastina, Jan - Liscak, R - Urgosik, D - Starek, Z - Crha, M - Lewis, O - Wooley, M - Johnson, D - Brouwers, CC - Evers, M - Motlik, J - Martens, GJM - Konstantinova, PS - Blits, B
PY - 2022
TI - Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas
JF - Journal of Neuroscience Methods
VL - 365
PB - ELSEVIER SCIENCE BV
SN - 01650270
N1 - Bez afiliace k MU.
KW - AAV
KW - CED
KW - Minipigs
KW - CNS
N2 - Background: As a step towards clinical use of AAV-mediated gene therapy, brains of large animals are used to settle delivery parameters as most brain connections, and relative sizes in large animals and primates, are reasonably common. Prior to application in the clinic, approaches that have shown to be successful in rodent models are tested in larger animal species, such as dogs, non-human primates, and in this case, minipigs. New method: We evaluated alternate delivery routes to target the basal ganglia by injections into the more su-perficial corona radiata, and, deeper into the brain, the thalamus. Anatomically known connections can be used to predict the expression of the transgene following infusion of AAV5. For optimal control over delivery of the vector with regards to anatomical location in the brain and spread in the tissue, we have used magnetic reso-nance image-guided convection-enhanced diffusion delivery. Results: While the transduction of the cortex was observed, only partial transduction of the basal ganglia was achieved via the corona radiata. Thalamic administration, on the other hand, resulted in widespread trans-duction from the midbrain to the frontal cortex Comparison with existing methods: Compared to other methods, such as delivery directly to the striatum, thalamic injection may provide an alternative when for instance, injection into the basal ganglia directly is not feasible. Conclusions: The study results suggest that thalamic administration of AAV5 has significant potential for in-dications where the transduction of specific areas of the brain is required.
ER -
PIETERSZ, KL, S POUW, J KLIMA, Z ELLEDEROVA, B BOHUSLAVOVA, Jan CHRASTINA, R LISCAK, D URGOSIK, Z STAREK, M CRHA, O LEWIS, M WOOLEY, D JOHNSON, CC BROUWERS, M EVERS, J MOTLIK, GJM MARTENS, PS KONSTANTINOVA and B BLITS. Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas. \textit{Journal of Neuroscience Methods}. AMSTERDAM: ELSEVIER SCIENCE BV, 2022, vol.~365, 9 pp. ISSN~0165-0270. Available from: https://dx.doi.org/10.1016/j.jneumeth.2021.109382.
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