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. 2024 Sep 5;52(18):10754–10774. doi: 10.1093/nar/gkae741

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© The Author(s) 2024. 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. — Off-target effect caused by the seed match sequence. (A) Mechanism of on- and off-target effects. Target gene suppression is caused by a full-match siRNA guide strand. Seed-match siRNA guide strands bind to non-target mRNA only in the seed region and cause off-target effects. (B) Effect of introducing chemical modifications in the seed region. Full-match siRNA guide strands can cause target gene suppression even if chemical modification is introduced into the seed region. Seed-matched siRNA guide strands cannot bind non-target mRNA because of chemical modification, and the off-target effect is suppressed.