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Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates

Non-human primates (NHPs) are precious resources for cutting-edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing the surgical preparation practices of convection-enhanced delivery (CED), wh...

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Autores principales: Griggs, Devon J., Garcia, Aaron D., Au, Wing Yun, Ojemann, William K. S., Johnson, Andrew Graham, Ting, Jonathan T., Buffalo, Elizabeth A., Yazdan-Shahmorad, Azadeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323200/
https://www.ncbi.nlm.nih.gov/pubmed/35890331
http://dx.doi.org/10.3390/pharmaceutics14071435
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author Griggs, Devon J.
Garcia, Aaron D.
Au, Wing Yun
Ojemann, William K. S.
Johnson, Andrew Graham
Ting, Jonathan T.
Buffalo, Elizabeth A.
Yazdan-Shahmorad, Azadeh
author_facet Griggs, Devon J.
Garcia, Aaron D.
Au, Wing Yun
Ojemann, William K. S.
Johnson, Andrew Graham
Ting, Jonathan T.
Buffalo, Elizabeth A.
Yazdan-Shahmorad, Azadeh
author_sort Griggs, Devon J.
collection PubMed
description Non-human primates (NHPs) are precious resources for cutting-edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing the surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs’. Here, we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe, and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks.
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spelling pubmed-93232002022-07-27 Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates Griggs, Devon J. Garcia, Aaron D. Au, Wing Yun Ojemann, William K. S. Johnson, Andrew Graham Ting, Jonathan T. Buffalo, Elizabeth A. Yazdan-Shahmorad, Azadeh Pharmaceutics Article Non-human primates (NHPs) are precious resources for cutting-edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing the surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs’. Here, we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe, and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks. MDPI 2022-07-08 /pmc/articles/PMC9323200/ /pubmed/35890331 http://dx.doi.org/10.3390/pharmaceutics14071435 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Griggs, Devon J.
Garcia, Aaron D.
Au, Wing Yun
Ojemann, William K. S.
Johnson, Andrew Graham
Ting, Jonathan T.
Buffalo, Elizabeth A.
Yazdan-Shahmorad, Azadeh
Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates
title Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates
title_full Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates
title_fullStr Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates
title_full_unstemmed Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates
title_short Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates
title_sort improving the efficacy and accessibility of intracranial viral vector delivery in non-human primates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323200/
https://www.ncbi.nlm.nih.gov/pubmed/35890331
http://dx.doi.org/10.3390/pharmaceutics14071435
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