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. 2024 Oct 2;16(11):2882–2917. doi: 10.1038/s44321-024-00148-5

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

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(A) qPCR of total genomic DNA extracted from both peripheral and CNS tissues showing viral distribution of treated mice through ICM or IV delivery; cerebrum, spinal cord, cerebellum, heart, and liver. (B–F) RT-qPCR of total RNA extracted from CNS (cerebrum; cerebellum; spinal cord) and peripheral tissues (heart; liver) hAP4B1 mRNA expression in ICM delivery treated mice is elevated in the cerebrum, cerebellum, spinal cord compared to IV delivery. (G) Western blot detection of Ap4e1 showed a partial rescue of the Ap4e1 protein in the cerebrum ICM delivery, and no rescue with IV delivery. (H) Relative expression analysis displayed Ap4e1 was significantly increased in the cerebrum with ICM treatment. (I) Western blot detection of Ap4e1 showed a partial rescue of the Ap4e1 protein in the spinal cord ICM delivery, and no rescue with IV delivery. (J) Relative expression analysis displayed Ap4e1 was significantly increased in the spinal cord with ICM treatment. (K) Western blot detection of Ap4e1 showed a partial rescue of the Ap4e1 protein in the cerebellum ICM delivery, and no rescue with IV delivery. (L) Relative expression analysis revealed Ap4e1 was significantly increased in the cerebellum with ICM treatment. All data are presented as mean ± SEM, n = 3 mice. (B–F) were analysed via a one-way ANOVA with Tukey’s multiple comparisons test. (H), (J) and (L) were analysed via unpaired t-test. Stars indicate p ≤ 0.05 (*); p ≤ 0.01 (**); p ≤ 0.001 (***); ns = not significant. (B), p = 0.0001; (C), p = 0.0206; (D), p = 0.0312; (H), p = 0.0111; (J), p = 0.0049; (L), p = 0.0207. Source data are available online for this figure.