Oligonucleotide Toxicity (OligoTox) Open Data Challenge

The Oligonucleotide Toxicity (OligoTox) Open Data Challenge is a two-phase competition administered by the National Center for Advancing Translational Sciences (NCATS), a center within the U.S. National Institutes of Health (NIH). The initiative is established under the authority of the America COMPETES Reauthorization Act of 2010 [15 U.S.C. § 3719]. This challenge is designed to promote the generation and public sharing of high-quality datasets that can improve predictive models of toxicity in oligonucleotide therapeutics. Oligonucleotides, often referred to as “oligos,” are short nucleic acid sequences that are chemically modified for therapeutic use, particularly in treating rare genetic conditions. With 17 FDA-approved oligo therapeutics currently on the market and more in development, concerns around toxicity—whether sequence-specific or not—remain a significant barrier to broader clinical adoption. Traditional methods of evaluating oligo toxicity rely heavily on animal studies, which are time-consuming, expensive, and increasingly seen as limited in relevance to human biology. Reflecting a broader shift in preclinical evaluation paradigms, both the FDA and NIH are encouraging the development of non-animal-based testing platforms. These include microphysiological systems, 3D human organoids, and advanced computational models, all of which promise improved predictive accuracy for human outcomes. However, a major limitation in the field is the lack of publicly accessible, high-quality datasets that can be used to train these in silico tools. Most existing toxicology datasets are proprietary and derived from animal models, creating a bottleneck in the development of more human-relevant predictive platforms. The OligoTox Challenge aims to address this data gap by incentivizing participants to generate and share datasets derived from in vitro human-based systems. These datasets should support the development of predictive models for various forms of oligo toxicity, such as hepatotoxicity, nephrotoxicity, immunotoxicity, thrombocytopenia, and coagulopathy, among others. Priority will be given to data that target underrepresented toxicity types, as large datasets for certain categories like acute neurotoxicity are already available. The challenge encourages the integration of both human-based and supplemental animal or in vitro data to strengthen the utility of the generated datasets. Phase 1, known as the Ideation Phase, is focused on gathering proposals for the types of datasets that could be generated. Proposals must define the toxicity indicators, predictor variables, sources, collection methods, and validation strategies, as well as include plans for dataset openness, use of positive and negative controls, and proposed model systems. Submissions are limited to 10 pages, not including references. Successful Phase 1 participants will be awarded cash prizes and will be encouraged to continue to Phase 2, though participation in Phase 1 is not required for entry into Phase 2. The second phase, the Data Generation Phase, will run for nine months and requires participants to create a fully accessible dataset aligned with FAIR data principles. The Phase 2 submission must include a narrative, a methodology document, a data file or access protocol, and a Public Access and Dissemination Plan (PADP). These materials must explain how the data were generated, describe the experimental design and variables, and define licensing and sharing terms. Submissions must include full metadata, oligo sequences, modification locations, and purity data. While optional, code documentation and tutorials are encouraged to facilitate broader usability. Applications for Phase 1 will open on December 17, 2025, and close on February 28, 2026. Judging will take place from March 1 to April 17, 2026, with winners announced on April 30, 2026. Phase 2 will begin on May 1, 2026, with submissions due by December 31, 2026. Judging for Phase 2 will occur from January 8 to February 28, 2027, with winners announced in March 2027. Technical assistance webinars are scheduled for both phases, providing potential applicants with opportunities to ask questions. For additional inquiries, participants may contact [email protected].