SafeSense: An open-access safety atlas for antisense oligonucleotides adverse events in human

Antisense oligonucleotides (ASOs) therapeutics are a powerful class of RNA-targeted therapy, with applications ranging from traditional development pipelines to individualized drugs. ASO therapeutics share common chemical architecture, including modifications and structure, thus enabling cross-program safety analyses, which provide insights into class-specific safety liabilities. Here, we present SafeSense, a safety atlas specifically dedicated to ASOs, integrating adverse event (AE) in human, encompassing data for 112 ASOs, curated in collaboration with the preclinical working group of the N = 1 collaborative (N1C). This resource was curated by aggregation and harmonization of data from clinical trials, regulatory documents, post-marketing data, and more. The data were used for internal analyses, and is now available as an open-access resource, available for public inquiries. Using advanced analyses, we identify several detriments of ASO safety, including structural configuration, sugar chemistries, administration route, and backbone compositions. Collectively, our findings provide a systematic overview of clinical ASO safety and reveal chemical architecture as a primary determinant of tolerability. By integrating heterogeneous safety data into a publicly available and analysis-ready framework, SafeSense provides a valuable resource for guiding ASO design, safety benchmarking, and clinical monitoring strategies, particularly useful for emerging personalized oligonucleotide therapies.