Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice

Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice

Mingxing Wang, Bo Wu, Jason D Tucker, Peijuan Lu, Qilong Lu Department of Neurology, McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, NC, USA Abstract: In this study, we investigated a series of cationic polyelectroly...

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Autores principales: Wang M, Wu B, Tucker JD, Lu P, Lu Q
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/4a81c10a68f34e7894891ff831b9b783
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spelling oai:doaj.org-article:4a81c10a68f34e7894891ff831b9b7832021-12-02T02:28:14ZCationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice1178-2013https://doaj.org/article/4a81c10a68f34e7894891ff831b9b7832015-09-01T00:00:00Zhttps://www.dovepress.com/cationic-polyelectrolyte-mediated-delivery-ofnbspantisense-morpholino--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mingxing Wang, Bo Wu, Jason D Tucker, Peijuan Lu, Qilong Lu Department of Neurology, McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, NC, USA Abstract: In this study, we investigated a series of cationic polyelectrolytes (PEs) with different size and composition for their potential to improve delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. The results showed that the poly(diallyldimethylammonium chloride) (PDDAC) polymer series, especially PE-3 and PE-4, improves the delivery efficiency of PMO, comparable with Endoporter-mediated PMO delivery in vitro. The enhanced PMO delivery and targeting to dystrophin exon 23 was further observed in mdx mice, up to fourfold with the PE-4, compared with PMO alone. The cytotoxicity of the PEs was lower than that of Endoporter and polyethylenimine 25,000 Da in vitro, and was not clearly detected in muscle in vivo under the tested concentrations. Together, these results demonstrate that optimization of PE molecular size, composition, and distribution of cationic charge are key factors to achieve enhanced PMO exon-skipping efficiency. The increased efficiency and lower toxicity show this PDDAC series to be capable gene/antisense oligonucleotide delivery-enhancing agents for treating muscular dystrophy and other diseases. Keywords: cationic polyelectrolytes, antisense delivery, exon-skipping, PMO, muscular dystrophyWang MWu BTucker JDLu PLu QDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5635-5646 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wang M
Wu B
Tucker JD
Lu P
Lu Q
Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
description Mingxing Wang, Bo Wu, Jason D Tucker, Peijuan Lu, Qilong Lu Department of Neurology, McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, NC, USA Abstract: In this study, we investigated a series of cationic polyelectrolytes (PEs) with different size and composition for their potential to improve delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. The results showed that the poly(diallyldimethylammonium chloride) (PDDAC) polymer series, especially PE-3 and PE-4, improves the delivery efficiency of PMO, comparable with Endoporter-mediated PMO delivery in vitro. The enhanced PMO delivery and targeting to dystrophin exon 23 was further observed in mdx mice, up to fourfold with the PE-4, compared with PMO alone. The cytotoxicity of the PEs was lower than that of Endoporter and polyethylenimine 25,000 Da in vitro, and was not clearly detected in muscle in vivo under the tested concentrations. Together, these results demonstrate that optimization of PE molecular size, composition, and distribution of cationic charge are key factors to achieve enhanced PMO exon-skipping efficiency. The increased efficiency and lower toxicity show this PDDAC series to be capable gene/antisense oligonucleotide delivery-enhancing agents for treating muscular dystrophy and other diseases. Keywords: cationic polyelectrolytes, antisense delivery, exon-skipping, PMO, muscular dystrophy
format article
author Wang M
Wu B
Tucker JD
Lu P
Lu Q
author_facet Wang M
Wu B
Tucker JD
Lu P
Lu Q
author_sort Wang M
title Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
title_short Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
title_full Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
title_fullStr Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
title_full_unstemmed Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
title_sort cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/4a81c10a68f34e7894891ff831b9b783
work_keys_str_mv AT wangm cationicpolyelectrolytemediateddeliveryofnbspantisensemorpholinooligonucleotidesforexonskippinginvitroandinmdxmice
AT wub cationicpolyelectrolytemediateddeliveryofnbspantisensemorpholinooligonucleotidesforexonskippinginvitroandinmdxmice
AT tuckerjd cationicpolyelectrolytemediateddeliveryofnbspantisensemorpholinooligonucleotidesforexonskippinginvitroandinmdxmice
AT lup cationicpolyelectrolytemediateddeliveryofnbspantisensemorpholinooligonucleotidesforexonskippinginvitroandinmdxmice
AT luq cationicpolyelectrolytemediateddeliveryofnbspantisensemorpholinooligonucleotidesforexonskippinginvitroandinmdxmice
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