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- W2097576232 abstract "Abstract Background Antisense oligonucleotides are promising medicines for treating various diseases, although their efficiency still requires high doses. Their delivery in the cytosol and nucleus to reach their mRNA targets would increase their efficiency at the same time as reducing the dose. Methods We conjugated the histidine‐rich peptide H5WYG (GLFHAIAHFIHGGWHGLIHGWYG) at the 5'‐end of the RNase H‐incompetent antisense 2'‐ O ‐methyl‐phosphodiester oligonucleotide (2'‐Ome RNA705) targeting aberrant splicing of luciferase pre‐mRNA in HeLa pLuc705 cells. H5WYG was also conjugated with 2'‐Ome‐RNA705 labelled by fluorescein at the 3'‐end. Then, H5WYG‐2'‐Ome‐RNA705 conjugate and 2'‐Ome‐RNA705 were formulated with lipofectamine to favor their uptake in HeLa pLuc705 cells. Results Confocal microscopy showed that, after 4 h and overnight incubation, the presence of fluorescein‐labelled 2'‐Ome‐RNA705 in the cytosol and nucleus was enhanced when the oligonucleotide was conjugated with H5WYG. We found that H5WYG‐2'‐Ome‐RNA705 increased the splicing redirection and restoration of a functional luciferase mRNA. Luciferase activity and luciferase mRNA levels in these cells were 6.6‐ and two‐fold higher, respectively, with H5WYG‐2'‐Ome‐RNA705 than with 2'‐Ome‐RNA705. Conclusions The results of the present study show that the conjugation of 2'‐Ome antisense RNA to peptide H5WYG is a good strategy for improving its cytosol delivery, accumulation in the nucleus and antisense activity. Copyright © 2014 John Wiley & Sons, Ltd." @default.
- W2097576232 created "2016-06-24" @default.
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- W2097576232 date "2014-07-01" @default.
- W2097576232 modified "2023-10-06" @default.
- W2097576232 title "Improved nuclear delivery of antisense 2′-Ome RNA by conjugation with the histidine-rich peptide H5WYG" @default.
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- W2097576232 doi "https://doi.org/10.1002/jgm.2773" @default.
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