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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 2. — Controlling MsPA chirality is not beneficial for improving therapeutic index or nuclease stability. (A) Design of chiral MsPA gapmer ASOs evaluated. (B) Synthesis of chiral MsPA ASOs using OAP chemistry. (C) Design, Tm, cytotoxicity and antisense activity of ASOs with chiral MsPA linkages. Position of the MsPA linkages are shown while the rest of the ASO is stereorandom PS modified. (D) Dose-response curves for reducing CXCl12 mRNA in NIH3T3 cells. (E) Sequence and (F) evaluation of MsPA oligonucleotides for stability versus exonuclease digestion using snake venom phosphodiesterase (SVPD). Blue letters indicate cEt, black DNA, subscript pink u = MsPA, green u = Sp MsPA, red u = Rp MsPA, s = PS, o = PO, superscript m = 5-Me group on cytosine nucleobases.