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Issue 97, 2016
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Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro

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Abstract

Twisted intercalating nucleic acids (TINA)-modified oligonucleotides containing phenylethynylpyren-1-yl derivatives were reported to improve the thermal stability of the nucleic acid duplexes, triplexes and G-quadruplexes. In the present study, we have investigated the potential of TINA-modified antisense oligonucleotides (AOs) in splice modulation by induced exon-skipping in vitro. We used both para-TINA (p-TINA) and ortho-TINA (o-TINA)-modified 2′-O-methyl (2′-OMe) AOs on a phosphorothioate backbone (PS) designed to skip exon-23 in dystrophin pre-mRNA transcript in mdx mice myotubes. A fully-modified 2′-OMePS AO control was used in parallel. Our results showed that both p-TINA and o-TINA-modified AOs were able to induce exon-23 skipping. These results provide new insights on expanding the applicability of TINA-modified oligonucleotides.

Graphical abstract: Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro

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Publication details

The article was received on 07 Sep 2016, accepted on 23 Sep 2016 and first published on 27 Sep 2016


Article type: Communication
DOI: 10.1039/C6RA22346J
Citation: RSC Adv., 2016,6, 95169-95172
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    Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro

    B. T. Le, V. V. Filichev and R. N. Veedu, RSC Adv., 2016, 6, 95169
    DOI: 10.1039/C6RA22346J

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