Abstract
RNA interference mediated by small interfering RNA (siRNA) has been widely used as a procedure to knock down the expression of an intended target gene with perfect sequence complementarity. However, siRNA often exhibits off-target effects on genes with partial sequence complementarities. Such off-target effect is an undesirable adverse effect for knocking down a target gene specifically. Here we describe the powerful strategy to avoid off-target effects without affecting the RNAi activity by the introduction of DNA or 2′-O-methyl modifications in the siRNA seed region. These two types of chemical modifications repress off-target effects through different molecular mechanisms.
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Acknowledgment
This work was financially supported by the Grants-in-Aid for Scientific Research (B) (No. 15H04319) and on Innovative Areas (No. 26102713) from the Ministry of Education, Culture, Sports, Science and Technology and Japan Society for the Promotion of Science, and by the grant from the Suzuken Memorial Foundation to Kumiko Ui-Tei. We used figure data rearranged with original previous report [13].
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Kobayashi, Y., Miyamoto, K., Aida, M., Ui-Tei, K. (2021). Selection of Chemical Modifications in the siRNA Seed Region That Repress Off-Target Effect. In: Ditzel, H.J., Tuttolomondo, M., Kauppinen, S. (eds) Design and Delivery of SiRNA Therapeutics. Methods in Molecular Biology, vol 2282. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1298-9_2
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DOI: https://doi.org/10.1007/978-1-0716-1298-9_2
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