Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect

Although antisense oligonucleotide (ASO) therapeutics can be taken up by living cells without carrier molecules, a large part of incorporated ASOs are trapped in the endosomes and do not exert therapeutic effects. To improve their therapeutic effects, it would be important to elucidate the mechanism...

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Autores principales:	Masayuki Takahashi, Mineaki Seki, Masayuki Nashimoto, Tomohiro Kabuta
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Genetics QH426-470 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/6bbd43e111d942ffb5f9e3594e13f4dc
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spelling	oai:doaj.org-article:6bbd43e111d942ffb5f9e3594e13f4dc2021-11-29T00:56:10ZPerturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect2090-021X10.1155/2021/2458470https://doaj.org/article/6bbd43e111d942ffb5f9e3594e13f4dc2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/2458470https://doaj.org/toc/2090-021XAlthough antisense oligonucleotide (ASO) therapeutics can be taken up by living cells without carrier molecules, a large part of incorporated ASOs are trapped in the endosomes and do not exert therapeutic effects. To improve their therapeutic effects, it would be important to elucidate the mechanism of cellular uptake and intracellular trafficking of ASOs. In this study, we investigated how SIDT1 affects cellular uptake and intracellular trafficking of ASOs. Fluorescence microscopic analysis suggested that most of naked ASOs are trafficked to the lysosomes via the endosomes. The data obtained from flow cytometry and fluorescence microscopy together showed that although the SIDT1 level barely affects the total cellular uptake of ASOs, it appears to affect the intracellular trafficking of ASOs. We also showed that SIDT1 exists mainly in the endoplasmic reticulum and that perturbing the normal level of SIDT1 suppresses the antisense effect of the naked ASO targeting miR-16.Masayuki TakahashiMineaki SekiMasayuki NashimotoTomohiro KabutaHindawi LimitedarticleGeneticsQH426-470BiochemistryQD415-436ENJournal of Nucleic Acids, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470 Biochemistry QD415-436
spellingShingle	Genetics QH426-470 Biochemistry QD415-436 Masayuki Takahashi Mineaki Seki Masayuki Nashimoto Tomohiro Kabuta Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
description	Although antisense oligonucleotide (ASO) therapeutics can be taken up by living cells without carrier molecules, a large part of incorporated ASOs are trapped in the endosomes and do not exert therapeutic effects. To improve their therapeutic effects, it would be important to elucidate the mechanism of cellular uptake and intracellular trafficking of ASOs. In this study, we investigated how SIDT1 affects cellular uptake and intracellular trafficking of ASOs. Fluorescence microscopic analysis suggested that most of naked ASOs are trafficked to the lysosomes via the endosomes. The data obtained from flow cytometry and fluorescence microscopy together showed that although the SIDT1 level barely affects the total cellular uptake of ASOs, it appears to affect the intracellular trafficking of ASOs. We also showed that SIDT1 exists mainly in the endoplasmic reticulum and that perturbing the normal level of SIDT1 suppresses the antisense effect of the naked ASO targeting miR-16.
format	article
author	Masayuki Takahashi Mineaki Seki Masayuki Nashimoto Tomohiro Kabuta
author_facet	Masayuki Takahashi Mineaki Seki Masayuki Nashimoto Tomohiro Kabuta
author_sort	Masayuki Takahashi
title	Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
title_short	Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
title_full	Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
title_fullStr	Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
title_full_unstemmed	Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
title_sort	perturbing the normal level of sidt1 suppresses the naked aso effect
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/6bbd43e111d942ffb5f9e3594e13f4dc
work_keys_str_mv	AT masayukitakahashi perturbingthenormallevelofsidt1suppressesthenakedasoeffect AT mineakiseki perturbingthenormallevelofsidt1suppressesthenakedasoeffect AT masayukinashimoto perturbingthenormallevelofsidt1suppressesthenakedasoeffect AT tomohirokabuta perturbingthenormallevelofsidt1suppressesthenakedasoeffect
_version_	1718407712858963968

Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect

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