The N=1 Collaborative: advancing customized nucleic acid therapies through collaboration and data sharing

Developing customized gene-targeting therapies for the millions of individuals affected by ultra-rare diseases globally requires breaking new ground in therapeutic and regulatory innovation. To address this need, the N=1 Collaborative (N1C) was established to unite academia, industry, patients, and regulators, building an open, shared ecosystem for personalized medicines. Initially focusing on antisense oligonucleotides (ASOs) for rare, fatal neurodegenerative conditions, the N1C aims to develop frameworks that can rapidly extend to other treatment modalities and conditions. Progress in the advancement of personalized therapies has also propelled advancements in the nucleic acids field, offering critical insights into dosing, safety, and efficacy. In October 2024, the N1C convened scientific, regulatory, and advocacy leaders in ASO development for an inaugural meeting. This review report examines the current state of the scientific and clinical ecosystems enabling customized genetic therapies and explores the innovation, frameworks, and systems needed to deliver additional individualized medicines safely and at scale.