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. 2021 Aug 20;49(16):9026–9041. doi: 10.1093/nar/gkab718

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© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 1. — MsPA enhances the therapeutic index of PS gapmer ASOs. (A) Design of gapmers and gap-modifications that enhance therapeutic index. (B) Synthesis of PO, PS and MsPA ASOs. (C) Design, Tm, cytotoxicity and antisense activity of ASOs with full MsPA in gap and/or wings. (D) Dose-response curves for reducing CXCl12 mRNA in NIH 3T3 cells. (E) Design, Tm, cytotoxicity and antisense activity of ASOs with two MsPA walked across length of ASO. (F) Dose-response curves for reducing CXCl12 mRNA in NIH 3T3 cells. Blue letters indicate cEt, black DNA, subscript u = MsPA, s = PS, superscript m = 5-Me group on cytosine nucleobases.