Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery

Abstract To optimize gene delivery to myelinating Schwann cells we compared clinically relevant AAV serotypes and injection routes. AAV9 and AAVrh10 vectors expressing either EGFP or the neuropathy-associated gene GJB1/Connexin32 (Cx32) under a myelin specific promoter were injected intrathecally or...

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Autores principales:	A. Kagiava, J. Richter, C. Tryfonos, M. Leal-Julià, I. Sargiannidou, C. Christodoulou, A. Bosch, K. A. Kleopa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e16780b5a43469086b07ce6b9a5240d
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spelling	oai:doaj.org-article:8e16780b5a43469086b07ce6b9a5240d2021-12-05T12:15:07ZEfficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery10.1038/s41598-021-02694-12045-2322https://doaj.org/article/8e16780b5a43469086b07ce6b9a5240d2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02694-1https://doaj.org/toc/2045-2322Abstract To optimize gene delivery to myelinating Schwann cells we compared clinically relevant AAV serotypes and injection routes. AAV9 and AAVrh10 vectors expressing either EGFP or the neuropathy-associated gene GJB1/Connexin32 (Cx32) under a myelin specific promoter were injected intrathecally or intravenously in wild type and Gjb1-null mice, respectively. Vector biodistribution in lumbar roots and sciatic nerves was higher in AAVrh10 injected mice while EGFP and Cx32 expression rates and levels were similar between the two serotypes. A gradient of biodistribution away from the injection site was seen with both intrathecal and intravenous delivery, while similar expression rates were achieved despite higher vector amounts injected intravenously. Quantified immune cells in relevant tissues were similar to non-injected littermates. Overall, AAV9 and AAVrh10 efficiently transduce Schwann cells throughout the peripheral nervous system with both clinically relevant routes of administration, although AAV9 and intrathecal injection may offer a more efficient approach for treating demyelinating neuropathies.A. KagiavaJ. RichterC. TryfonosM. Leal-JuliàI. SargiannidouC. ChristodoulouA. BoschK. A. KleopaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. Kagiava J. Richter C. Tryfonos M. Leal-Julià I. Sargiannidou C. Christodoulou A. Bosch K. A. Kleopa Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
description	Abstract To optimize gene delivery to myelinating Schwann cells we compared clinically relevant AAV serotypes and injection routes. AAV9 and AAVrh10 vectors expressing either EGFP or the neuropathy-associated gene GJB1/Connexin32 (Cx32) under a myelin specific promoter were injected intrathecally or intravenously in wild type and Gjb1-null mice, respectively. Vector biodistribution in lumbar roots and sciatic nerves was higher in AAVrh10 injected mice while EGFP and Cx32 expression rates and levels were similar between the two serotypes. A gradient of biodistribution away from the injection site was seen with both intrathecal and intravenous delivery, while similar expression rates were achieved despite higher vector amounts injected intravenously. Quantified immune cells in relevant tissues were similar to non-injected littermates. Overall, AAV9 and AAVrh10 efficiently transduce Schwann cells throughout the peripheral nervous system with both clinically relevant routes of administration, although AAV9 and intrathecal injection may offer a more efficient approach for treating demyelinating neuropathies.
format	article
author	A. Kagiava J. Richter C. Tryfonos M. Leal-Julià I. Sargiannidou C. Christodoulou A. Bosch K. A. Kleopa
author_facet	A. Kagiava J. Richter C. Tryfonos M. Leal-Julià I. Sargiannidou C. Christodoulou A. Bosch K. A. Kleopa
author_sort	A. Kagiava
title	Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
title_short	Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
title_full	Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
title_fullStr	Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
title_full_unstemmed	Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
title_sort	efficacy of aav serotypes to target schwann cells after intrathecal and intravenous delivery
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8e16780b5a43469086b07ce6b9a5240d
work_keys_str_mv	AT akagiava efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT jrichter efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT ctryfonos efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT mlealjulia efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT isargiannidou efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT cchristodoulou efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT abosch efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery AT kakleopa efficacyofaavserotypestotargetschwanncellsafterintrathecalandintravenousdelivery
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Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery

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