Gene-based therapies have begun to change the options and outcomes for patients with rare and ultra-rare genetic disorders. Availability of these therapies is limited by cost, risk of failure, challenges in manufacturing, and novel regulatory requirements. Furthermore, institutions differ widely in the resources, expertise, and risk tolerance they can apply to providing patients with such individualized therapies. NINDS seeks to create a mechanism that enables wider development and deployment of gene-based therapies. In April 2019, a workshop entitled “Advancing Gene-Targeted Therapies for Central Nervous System Disorders” was held by the National Academy of Medicine. In September 2019, a workshop entitled “Next Generation Strategies for Gene-Targeted Therapies of Central Nervous System Disorders” was held by NINDS to convene thought leaders and experts in diverse aspects of gene therapy, including target gene regulation of expression, target distribution, development of preclinical assays and models, choice of viral vector or delivery system, manufacture and scale-up, clinical trial challenges, collaborative network models, and regulatory requirements and standards. Finally, in December 2019, a meeting entitled “Facilitating Access to Gene Therapy for Rare Diseases: Opportunities for Collaboration” was held by the Foundation for NIH (FNIH) to bring together experts from the government, academia, industry, and nonprofit advocacy sectors to prioritize challenges, such as preclinical scientific, technical, regulatory, and quality of life, for study and solution. FNIH has since launched an effort to create an atlas of adeno-associated viral vector platforms; NCATS has also initiated platform strategies with which to begin performance of gene therapy trials for systemic and neuromuscular junction disorders. The culmination of our efforts results in the ongoing formation of the Ultra-Rare Gene-based Therapy (URGenT) network - an NINDS late-stage therapy development program that aims to speed the delivery of state-of-the-art gene-based therapies to patients with ultra-rare diseases of the nervous system, standardize and harmonize best practices, and encourage innovation in clinical trials. URGenT was approved by the NINDS Council in February 2020. The network will provide, on a competitive basis, both grant funding and access to in-kind resources for planning and execution of therapeutic agent optimization, scale up and manufacture, IND-enabling studies, regulatory affairs support including IND preparation and submission, and clinical trial performance. The first requests for applications are anticipated to be issued in 2021.