Abstract

Advanced nucleic-acid based therapeutics (NATs) e.g. antisense oligonucleotides (ASOs), siRNAs and modified in vitro transcribed mRNAs, can provide promising treatments ranging from mRNAs vaccines against COVID19 and cancers, to therapeutic ASOs to treat life-limiting genetic disorders. However, each therapy presents its own unique safety assessment challenges and preclinical studies have identified a range of toxicities for ASOs and siRNAs that are now observed in clinical trials. Understanding how NATs interact with and impact on the cellular machinery is key to preventing off-target effects and to improve the safety profiles of these new medicine platforms and this research is particularly important as we progress from using these new agents to treat rare to common diseases.

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