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. 2017 Oct 2;7:12532. doi: 10.1038/s41598-017-12844-z

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Comprehensive results of in vitro activity of gapmers designed to APP RNA 717 target (APP London variant). (A) Target APP mRNA sequence containing site of G-to-A (RNA717) SNP and designed to it antisense gapmers. SNP in RNA strand is bolded and underlined, codon in which it occurs is marked by red frame. Modified nucleotides within gapmers are marked by colours: blue-LNA, green-2′-O-MeRNA, bolded black- DNA, red-mismatched nucleotides, underlined-SNP site. (B) RNase H in vitro assay results for APP RNA717 target, showing the influence of arrangements of mismatched nucleotides in 13 nt-long RNA/ASO duplexes on RNase H cleavage. Blue frames mark gapmers which cause preferential cleavage of Mut RNA. Red frames mark gapmer which cause preferential cleavage of WT RNA. (C) Thermodynamic parameters of APP 717 wild type and mutant RNA/gapmer duplexes containing mismatches. Oligonucleotides, which differentiated two alleles cleavage yields in RNase H assay were only measured. Parameters for more stable duplex of the two (wild type/ASO or mutant/ASO) are bolded.