Considerations for assessment of reproductive and developmental toxicity of oligonucleotide-based therapeutics.

This white paper summarizes the current consensus of the Reproductive Subcommittee of the Oligonucleotide Safety Working Group on strategies to assess potential reproductive and/or developmental toxicities of therapeutic oligonucleotides (ONs). The unique product characteristics of ONs require considerations when planning developmental and reproductive toxicology studies, including (a) chemical characteristics, (b) assessment of intended and unintended mechanism of action, and (c) the optimal exposure, including dosing regimen. Because experience across the various classes of ONs as defined by their chemical backbone is relatively limited, best practices cannot be defined. Rather, points to consider are provided to help in the design of science-based reproductive safety evaluation programs based upon product attributes.