Biodistribution of Radioactively Labeled Splice Modulating Antisense Oligonucleotides After Intracerebroventricular and Intrathecal Injection in Mice
Antisense oligonucleotides (AONs) are promising therapeutic candidates, especially for neurological diseases. Intracerebroventricular (ICV) injection is the predominant route of administration in mouse studies, while in clinical trials, intrathecal (IT) administration is mostly used. There is little knowledge on the differences in distribution of these injection methods within the same species over time. In this study, we compared the distribution of splice-switching AONs targeting exon 15 of amyloid precursor protein pre-mRNA injected via the ICV and IT route in mice. The AON was labeled with radioactive indium-111 and mice were imaged using single-photon emission computed tomography (SPECT) 0, 4, 24, 48, 72, and 96 h after injection. In vivo SPECT imaging showed 111In-AON activity diffused throughout the central nervous system (CNS) in the first hours after injection. The 111In-AON activity in the CNS persisted over the course of 4 days, while signal in the kidneys rapidly decreased. Postmortem counting in different organs and tissues showed very similar distribution of 111In-AON activity throughout the body, while the signal in the different brain regions was higher with ICV injection. Overall, IT and ICV injection have very similar distribution patterns in the mouse, but ICV injection is much more effective in reaching the brain.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Nucleic acid therapeutics - 34(2024), 1 vom: 22. Feb., Seite 26-34 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Metz, Tom [VerfasserIn] |
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| Links: |
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| Themen: |
Antisense oligonucleotide |
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| Anmerkungen: |
Date Completed 23.02.2024 Date Revised 23.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1089/nat.2023.0018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368762904 |
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| 520 | |a Antisense oligonucleotides (AONs) are promising therapeutic candidates, especially for neurological diseases. Intracerebroventricular (ICV) injection is the predominant route of administration in mouse studies, while in clinical trials, intrathecal (IT) administration is mostly used. There is little knowledge on the differences in distribution of these injection methods within the same species over time. In this study, we compared the distribution of splice-switching AONs targeting exon 15 of amyloid precursor protein pre-mRNA injected via the ICV and IT route in mice. The AON was labeled with radioactive indium-111 and mice were imaged using single-photon emission computed tomography (SPECT) 0, 4, 24, 48, 72, and 96 h after injection. In vivo SPECT imaging showed 111In-AON activity diffused throughout the central nervous system (CNS) in the first hours after injection. The 111In-AON activity in the CNS persisted over the course of 4 days, while signal in the kidneys rapidly decreased. Postmortem counting in different organs and tissues showed very similar distribution of 111In-AON activity throughout the body, while the signal in the different brain regions was higher with ICV injection. Overall, IT and ICV injection have very similar distribution patterns in the mouse, but ICV injection is much more effective in reaching the brain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a SPECT imaging | |
| 650 | 4 | |a antisense oligonucleotide | |
| 650 | 4 | |a distribution | |
| 650 | 4 | |a intracerebroventricular administration | |
| 650 | 4 | |a intrathecal administration | |
| 650 | 4 | |a mouse brain | |
| 650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
| 700 | 1 | |a Welling, Mick M |e verfasserin |4 aut | |
| 700 | 1 | |a Suidgeest, Ernst |e verfasserin |4 aut | |
| 700 | 1 | |a Nieuwenhuize, Esmée |e verfasserin |4 aut | |
| 700 | 1 | |a de Vlaam, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Curtis, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Hailu, Tsinatkeab T |e verfasserin |4 aut | |
| 700 | 1 | |a van der Weerd, Louise |e verfasserin |4 aut | |
| 700 | 1 | |a van Roon-Mom, Willeke M C |e verfasserin |4 aut | |
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