Significance. Nucleic acid therapeutics (NATs) represent a transformative frontier in medicine, with numerous drugs already approved. This clinical success has been achieved through persistent technological innovation and successful adherence to two pivotal principles: understanding the molecular mechanisms of nucleic acid action and cellular interactions, and ensuring robust delivery systems. The clinical success of nucleic acid therapeutics in treating liver diseases is now a reality. The next frontiers in this field will emerge from several areas: advancements in chemistry and targeted delivery, exploration of novel mechanisms of therapeutic gene regulation, and the integration of informatics and AI-based design. Innovation. The diversity of nucleic acid molecular mechanisms—ranging from semi-permanent gene regulation and gene activation to readthrough codon skipping—profoundly enhances the possibilities for application and innovative treatments. Shared chemistry, fundamental delivery principles, and commonalities in intracellular interactions are consistent across various RNA-based drugs. While the potential of these emerging mechanisms is immense, there is a redundancy of learning within the community, necessitating a concerted effort to break these cycles. Thus, it is imperative to convene a diverse audience comprising experts in chemistry, cellular and molecular biology, and pharmacology to foster interdisciplinary exchange and cross-pollination of ideas. The overarching objective of the Keystone meeting is to catalyze such interactions, thereby providing the foundation for the next wave of transformative discoveries in the field. The co-organization with the precision genome editing session aims to further this agenda, recognizing the shared questions and solutions that transcend disciplinary boundaries. Together, we aim to chart a course towards a future where NATs realize their full potential in reshaping the landscape of medicine.