Thanks to the advent of genomic sequencing and numerous personalized medicine initiatives in various medical centers, it is now known that there are many patients who have heretofore never been diagnosed who have mutations that are unique to them and them only and others that may be members of an extremely rare mutation (<30 patients in the world). Although each mutation may be unique it is now estimated that there are millions of these unique or vanishingly small patient groups. Patients with diseases caused by ultra-rare mutations present challenges to the health care system that are as unique as their mutation. n-Lorem was founded to take advantage of the antisense technology that we created at Ionis to discover and develop personalized antisense oligonucleotides (ASOs) one patient at a time and provide those experimental ASO treatments for free for life. In our first 18 months of operation, we have demonstrated this goal is achievable and worked with the FDA to develop guidance for ASO treatment of patients with ultra-rare diseases. In this article, I define the problem, discuss the ASO solution, and our progress at n-Lorem to date. I then focus on important steps that we have taken to assure that these complex risk/benefit judgments are made with high quality and that each patient receives the highest quality ASO possible. I then describe the processes we have created to assure that the opportunity to learn from each patient and our aggregate experience are maximized and shared with all stakeholders.

中文翻译：

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一次满足一名患者的超罕见突变患者的需求：n-Lorem 方法

由于基因组测序的出现和各个医疗中心的众多个性化医疗计划，现在已知有许多迄今为止从未被诊断出的患者具有他们独有的突变，并且只有他们和其他可能是一种极其罕见的突变（世界上<30名患者）。尽管每个突变都可能是独特的，但现在估计有数百万个这些独特的或微乎其微的患者群体。患有由超罕见突变引起的疾病的患者对医疗保健系统提出了与他们的突变一样独特的挑战。n-Lorem 的成立是为了利用我们在 Ionis 创建的反义技术，一次发现和开发一个患者的个性化反义寡核苷酸 (ASO)，并终生免费提供这些实验性 ASO 治疗。在我们运营的前 18 个月中，我们证明了这一目标是可以实现的，并与 FDA 合作制定了 ASO 治疗超罕见疾病患者的指南。在本文中，我定义了问题，讨论了 ASO 解决方案，以及迄今为止我们在 n-Lorem 上的进展。然后，我将重点介绍我们已采取哪些重要步骤，以确保这些复杂的风险/收益判断是高质量的，并且每个患者都可能获得最高质量的 ASO。