Safety assessment oligonucleotides

Levin AA, Geary RS, Leeds JM, Monteith DK, Yu RZ,Templin MV, Henry SPThe pharmacokinetics and toxicity of phosphorothioate oligonucleotides. In Thomas JA, ed. Biotechnology and Safety Assessment. Philadelphia Taylor and Francis, 1998 151—75. 

For detailed information on safety assessment of vaccines (prophylactic and therapeutic), readers are referred to reviews on this topic (Lebron et al. 2005 Sun et al. 2012 Matsumoto et al. 2014). SP for bacterial- or mammalian cell-derived oligonucleotides is typically evaluated during repeat-dose toxicity studies (Dixit et al. 2010 Kim et al. 2014) however, recommendations and strategies that can be used to assess these unique agents have been developed by the SP subcommittee of the Oligonucleotide Safety Working Group (Schubert et al. 2012 Berman et al. 2014). 

Assessing the Safety Pharmacology of Oligonucleotide Therapeutic Agents The battery of safety pharmacology studies for oligonucleotide compounds can be ascertained from the ICFI guidance on the topic. 

There are other complex issues with regard to the assessment of safety pharmacology studies. With the oligonucleotide therapeutics that modulate the translation of mRNA to proteins, like antisense/siRNA, there is a lag between administration of the drug and the pharmacologic activity that is mediated by reduction in protein levels. This lag is related to the mechanism of action and how long it takes for a reduction in protein synthesis to be reflected in reduced protein levels. Because of this lag it is probably better to... 

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