Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
Kagiava, A. (The Cyprus Institute of Neurology and Genetics)
Richter, J. (The Cyprus Institute of Neurology and Genètics)
Tryfonos, C. (The Cyprus Institute of Neurology and Genetics)
Leal-Julià, Marc (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sargiannidou, I. (The Cyprus Institute of Neurology and Genetics)
Christodoulou, C. (The Cyprus Institute of Neurology and Genètics)
Bosch, A. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Kleopa, K. A. (The Cyprus Institute of Neurology and Genètics)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	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.
Ajuts:	Generalitat de Catalunya 2019FI_B2 00061 Fundació la Marató de TV3 201607.10
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Diseases of the nervous system ; Myelin biology and repair ; Peripheral nervous system
Publicat a:	Scientific reports, Vol. 11 (december 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-02694-1
PMID: 34857831

14 p, 2.2 MB

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