J 2022

Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas

PIETERSZ, KL, S POUW, J KLIMA, Z ELLEDEROVA, B BOHUSLAVOVA et. al.

Základní údaje

Originální název

Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas

Autoři

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 a B BLITS

Vydání

Journal of Neuroscience Methods, AMSTERDAM, ELSEVIER SCIENCE BV, 2022, 0165-0270

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.000

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/j.jneumeth.2021.109382

UT WoS

000710084300005

Klíčová slova anglicky

AAV; CED; Minipigs; CNS

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 27. 1. 2022 14:01, Mgr. Tereza Miškechová

Anotace

V originále

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.
Zobrazeno: 1. 11. 2024 21:29