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  • Second generation of antisense agents with segments of modified phosphorothioate oligonucleotides. The most extensively studied and used agents contain 2\'-substituted modifications, such as 2\'-O-methyl. In animal models, such modifications were associated with improved in vivo stability, oral bioavailability, and markedly decreased concentration-related adverse events that were common for the first generation of oligonucleotides and have been attributed to sequence-independent and sequence-specific effects. (NCI)
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