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

Nucleic Acids Research, vol. 53

Abstract

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.

Authors 8

1. Jillian Belgrad

   University of Massachusetts Chan Medical School

   Affiliation as printed

   N=1 Collaborative , Somerville , MA  02143,

   RNA Therapeutics Institute, University of Massachusetts Chan Medical School , Worcester , MA  01605,

2. Erin M. McConnell

   Carleton University

   Affiliation as printed

   Carleton University , Ottawa , ON, K1S 5B6, 

   N=1 Collaborative , Somerville , MA  02143,

3. Nicole Nolen
   Affiliation as printed

   N=1 Collaborative , Somerville , MA  02143,

4. Marlen C. Lauffer Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center Department of Human Genetics, , 2333 ZA  Leiden ,

   N=1 Collaborative , Somerville , MA  02143,

5. Jonathan K. Watts

   University of Massachusetts Chan Medical School

   Affiliation as printed

   N=1 Collaborative , Somerville , MA  02143,

   RNA Therapeutics Institute, University of Massachusetts Chan Medical School , Worcester , MA  01605,

6. Timothy W. Yu

   Boston Children's Hospital · Harvard University

   Affiliation as printed

   Division of Genetics and Genomics, Boston Children’s Hospital , Boston , MA 02115, 

   Harvard Medical School , Division of Medical Sciences,  Boston , MA, 02115,

   N=1 Collaborative , Somerville , MA  02143,

7. Winston X. Yan
   Affiliation as printed

   N=1 Collaborative , Somerville , MA  02143,

8. Annemieke M Aartsma-Rus corresponding Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center Department of Human Genetics, , 2333 ZA  Leiden ,

   N=1 Collaborative , Somerville , MA  02143,