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Structure-Guided Optimization of siRNA and Anti-miRNA Properties

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Handbook of Chemical Biology of Nucleic Acids
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Chemical modifications to therapeutic nucleic acids are used to modulate properties such as nuclease resistance, target engagement, enzymatic activity, and cell uptake. Therapeutic nucleic acids have different mechanisms of action and often engage nucleic acid binding proteins to elicit their effects. In some cases, high-resolution structures of important effector protein-RNA complexes are known and can be used to guide the design of chemical modifications of the therapeutic nucleic acid. This is the case for siRNAs and anti-miRNAs where crystal structures of RNA-bound complexes of the human effector protein Argonaute 2 (Ago2) have been reported along with structures of isolated domains of Ago2. In this chapter, examples of the use of these structures in the rational design of chemical modifications intended to improve siRNA or anti-miRNA properties are described.

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Correspondence to Peter A. Beal .

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© 2023 Springer Nature Singapore Pte Ltd.

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Pham, K.M., Beal, P.A. (2023). Structure-Guided Optimization of siRNA and Anti-miRNA Properties. In: Sugimoto, N. (eds) Handbook of Chemical Biology of Nucleic Acids. Springer, Singapore.

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-16-1313-5

  • Online ISBN: 978-981-16-1313-5

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