Genetic suppressors as new therapeutic targets for Mendelian diseases
Claire Paltenghi-Peceva 1 , Sabine van Schie 2 , Erfan Heidari 1 , Stephen Friend 3 , Jolanda van Leeuwen 4
Affiliations
- PMID: 42392954
- DOI: 10.1016/j.tig.2026.06.003
Abstract
Most Mendelian diseases lack effective treatments, with current options often limited to symptomatic care rather than addressing the underlying genetic defect. In this opinion article, we argue that genetic suppressors, a specific class of modifier variants that can counteract the effects of disease-causing mutations, can identify promising new avenues for therapeutic intervention. We discuss the prevalence of potential suppressors across Mendelian diseases, describe approaches for their systematic identification, and consider their therapeutic relevance. As genome-wide screening technologies and machine learning methods continue to advance, we expect suppressor identification to accelerate in the near future. These suppressors present exciting opportunities for expanding our therapeutic arsenal and improving outcomes for individuals with inherited disorders.