A lifetime with RNA: John J. Rossi and the questions that science revisits

Abstract

Dr. John J. Rossi's scientific career has unfolded alongside the transformation of RNA from a biological intermediary into a programmable therapeutic modality. Beginning with catalytic RNA and anti-HIV ribozymes, his work progressed through RNA interference, expressed siRNA and shRNA, combinatorial RNA gene therapy, and aptamer-guided delivery. This Editorial uses that trajectory to examine a broader feature of modern biomedicine: discovery and delivery must advance together, and scientific progress often depends on returning to unexplained observations with better tools. Rossi's roles at City of Hope and in building the oligonucleotide therapeutics community further show that continuity is sustained not only by experiments, but also by institutions, mentorship, and collaboration. His 2026 reflection on revisiting long-standing biological questions therefore offers a timely vantage on a career spent expanding what RNA can do. The resulting history links changing concepts of RNA with persistent questions of specificity, control, delivery, safety, and clinical translation across biomedicine.