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

Le, B.T., Filichev, V.V. and Veedu, R.N. (2016) Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro. RSC Advances, 6 (97). pp. 95169-95172.

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.

Item Type:	Journal Article
Murdoch Affiliation(s):	Centre for Comparative Genomics
Publisher:	Royal Society of Chemistry
Copyright:	© 2016 Royal Society of Chemistry
URI:	http://researchrepository.murdoch.edu.au/id/eprint/34205

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