Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages

Tissue macrophages, including microglia, are notoriously resistant to genetic manipulation. Here, we report the creation of Adeno-associated viruses (AAV) variants that efficiently and widely transduce microglia and tissue macrophages in vivo following intravenous delivery, with transgene expression...

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Autores principales: Young, Adam, Neumann, Bjoern, Segel, Michael, Chen, Civia Zi-Yu, Tourlomousis, Panagiotis, Franklin, Robin J. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469016/
https://www.ncbi.nlm.nih.gov/pubmed/37603759
http://dx.doi.org/10.1073/pnas.2302997120
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author Young, Adam
Neumann, Bjoern
Segel, Michael
Chen, Civia Zi-Yu
Tourlomousis, Panagiotis
Franklin, Robin J. M.
author_facet Young, Adam
Neumann, Bjoern
Segel, Michael
Chen, Civia Zi-Yu
Tourlomousis, Panagiotis
Franklin, Robin J. M.
author_sort Young, Adam
collection PubMed
description Tissue macrophages, including microglia, are notoriously resistant to genetic manipulation. Here, we report the creation of Adeno-associated viruses (AAV) variants that efficiently and widely transduce microglia and tissue macrophages in vivo following intravenous delivery, with transgene expression of up to 80%. We use this technology to demonstrate manipulation of microglia gene expression and microglial ablation, thereby providing invaluable research tools for the study of these important cells.
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spelling pubmed-104690162023-09-01 Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages Young, Adam Neumann, Bjoern Segel, Michael Chen, Civia Zi-Yu Tourlomousis, Panagiotis Franklin, Robin J. M. Proc Natl Acad Sci U S A Biological Sciences Tissue macrophages, including microglia, are notoriously resistant to genetic manipulation. Here, we report the creation of Adeno-associated viruses (AAV) variants that efficiently and widely transduce microglia and tissue macrophages in vivo following intravenous delivery, with transgene expression of up to 80%. We use this technology to demonstrate manipulation of microglia gene expression and microglial ablation, thereby providing invaluable research tools for the study of these important cells. National Academy of Sciences 2023-08-21 2023-08-29 /pmc/articles/PMC10469016/ /pubmed/37603759 http://dx.doi.org/10.1073/pnas.2302997120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Young, Adam
Neumann, Bjoern
Segel, Michael
Chen, Civia Zi-Yu
Tourlomousis, Panagiotis
Franklin, Robin J. M.
Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
title Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
title_full Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
title_fullStr Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
title_full_unstemmed Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
title_short Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
title_sort targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469016/
https://www.ncbi.nlm.nih.gov/pubmed/37603759
http://dx.doi.org/10.1073/pnas.2302997120
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