Individualized Antisense Oligonucleotide Therapies: How to Approach the Challenge of Manufacturing These Oligos from a Chemistry, Manufacturing, and Control-Regulatory Standpoint.

With the development of antisense oligonucleotides over more than 30 years and the increasing number of identified unique severely debilitating or life-threatening diseases affecting only 1 person in the world-now referred to as N-of-1 diseases-it is more and more appealing to use antisense technology to treat N-of-1 diseases when they are caused by well-identified mutations in single genes. N-of-1 patients present unique challenges to the health care system because the patient may be, and often is, the single patient in the world with the specific mutation in question, thus requiring an approach particular to that patient. Yet, we now know that there are millions of such patients, requiring scalable solutions. This article offers suggestions on how a specific and very regulated area of the new drug development process, chemistry, manufacturing, and control, could be addressed for N-of-1 oligonucleotides from a regulatory standpoint.