The National Center for Advancing Translational Sciences (NCATS) is seeking input from the scientific and research community on the development of advanced tools to predict the toxicity of oligonucleotide therapeutics, a critical step toward accelerating the safe and ethical advancement of these promising treatments. Oligonucleotide therapeutics (e.g., ASOs, siRNAs, miRNA mimics) hold major potential for treating rare genetic diseases, infectious diseases, and cancer. However, current toxicity assessments rely heavily on animal studies, which are costly, time-consuming, and increasingly being phased out by FDA guidance.
Information requested
The National Institutes of Health seeks responses from interested individuals to the following questions:
- For which tissues/organs/cell types is toxicity of most concern for oligo therapeutics development ?
- What publicly available datasets could be used to predict the toxicity of oligo therapeutics? What additional, currently unavailable datasets would be most useful? What datasets that do not exist currently would have the most value to predict the toxicity of oligo therapeutics?
- What would be the most effective way to assess the toxicity of chemical modifications to oligos in the context of different sequences (chemical modification X sequence interaction)?
- What approaches are currently being used to predict the toxicity of oligo therapeutics other than animal testing or human cell-based systems (micro physiological systems/organoids)?
- What would be the most effective way to assess the validity, accuracy, and robustness of predictive models for the toxicity of oligo therapeutics?
- What types of collaborative, team-science based approaches would be most effective for developing predictive models for the toxicity of oligo therapeutics?
Submit a response
All comments should be submitted via email at ncatsoligotox@mail.nih.gov. Deadline for responding: July 30, 2025, with a page limit of 5 pages.
More information available at the following link: https://grants.nih.gov/grants/guide/notice-files/NOT-TR-25-011.html