In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed. We discuss why the traditional drug development and reimbursement pathway is not fit for purpose in this field, and outline the pragmatic, regulatory and ethical challenges this poses for future access to N-of-1 therapies. Finally, we provide a roadmap for N-of-1 individualized therapy development.

近年来，少数由独特基因变异引起的罕见病患者接受了专门为他们开发的疗法。这一遗传 N-of-1 疗法的开创性领域正在迅速发展，为非常罕见疾病患者的个体化治疗带来了希望。在这篇综述中，我们概述了 N-of-1 个体化疗法的概念，重点是基因疗法，并使用已成功开发疗法的案例来说明该领域的进步和挑战。我们讨论了为什么传统的药物开发和报销途径不适合该领域的目的，并概述了这对未来获得 N-of-1 疗法构成的实用、监管和伦理挑战。最后，我们提供了 N-of-1 个体化疗法开发的路线图。