Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy

Linda J Popplewell; Aseel Abu-Dayya; Tushar Khanna; Marcella Flinterman; Nada Abdul Khalique; Liji Raju; Christer L Øpstad; Hans-Richard Sliwka; Vassilia Partali; George Dickson; Michael D Pungente

doi:10.3390/molecules17021138

Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy

Linda J Popplewell, Aseel Abu-Dayya, Tushar Khanna, Marcella Flinterman, Nada Abdul Khalique, Liji Raju, Christer L Øpstad, Hans-Richard Sliwka, Vassilia Partali, George Dickson, Michael D Pungente

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Abstract

Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).

Original language	English
Pages (from-to)	1138-1148
Number of pages	11
Journal	Molecules
Volume	17
Issue number	2
DOIs	https://doi.org/10.3390/molecules17021138
Publication status	Published - 24 Jan 2012
Externally published	Yes

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10.3390/molecules17021138Licence: CC BY

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Popplewell, L. J., Abu-Dayya, A., Khanna, T., Flinterman, M., Abdul Khalique, N., Raju, L., Øpstad, C. L., Sliwka, H.-R., Partali, V., Dickson, G., & Pungente, M. D. (2012). Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy. Molecules, 17(2), 1138-1148. https://doi.org/10.3390/molecules17021138

@article{221a935d894e4635933810d273cab699,

title = "Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy",

abstract = "Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).",

author = "Popplewell, {Linda J} and Aseel Abu-Dayya and Tushar Khanna and Marcella Flinterman and {Abdul Khalique}, Nada and Liji Raju and {\O}pstad, {Christer L} and Hans-Richard Sliwka and Vassilia Partali and George Dickson and Pungente, {Michael D}",

year = "2012",

month = jan,

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doi = "10.3390/molecules17021138",

language = "English",

volume = "17",

pages = "1138--1148",

journal = "Molecules",

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Popplewell, LJ, Abu-Dayya, A, Khanna, T, Flinterman, M, Abdul Khalique, N, Raju, L, Øpstad, CL, Sliwka, H-R, Partali, V, Dickson, G & Pungente, MD 2012, 'Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy', Molecules, vol. 17, no. 2, pp. 1138-1148. https://doi.org/10.3390/molecules17021138

TY - JOUR

T1 - Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy

AU - Popplewell, Linda J

AU - Abu-Dayya, Aseel

AU - Khanna, Tushar

AU - Flinterman, Marcella

AU - Abdul Khalique, Nada

AU - Raju, Liji

AU - Øpstad, Christer L

AU - Sliwka, Hans-Richard

AU - Partali, Vassilia

AU - Dickson, George

AU - Pungente, Michael D

PY - 2012/1/24

Y1 - 2012/1/24

N2 - Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).

AB - Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).

U2 - 10.3390/molecules17021138

DO - 10.3390/molecules17021138

M3 - Article

C2 - 22274137

SN - 1420-3049

VL - 17

SP - 1138

EP - 1148

JO - Molecules

JF - Molecules

IS - 2

ER -

Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy

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