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This includes a better understanding of the Janus-faced effects of various chemical modifications, such as phosphorothioate 8 , locked nucleic acid (LNA) 12 and 2-Fluoro (F) 13 , that, on the one hand, improve efficacy but, on the other hand, can cause toxicity, limiting their application in the clinic 1,8

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A structured dosing protocol helps balance effectiveness with tolerability