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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F22%3A00556565" target="_blank" >RIV/67985904:_____/22:00556565 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023884:_____/21:00009040 RIV/62157124:16170/22:43880481 RIV/00159816:_____/22:00077794

Výsledek na webu

<a href="https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=30122542985" target="_blank" >https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=30122542985</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jneumeth.2021.109382" target="_blank" >10.1016/j.jneumeth.2021.109382</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Neuroscience Methods

ISSN

0165-0270

e-ISSN

1872-678X

Svazek periodika

365

Číslo periodika v rámci svazku

Jan 1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

109382

Kód UT WoS článku

000710084300005

EID výsledku v databázi Scopus

2-s2.0-85117338482