Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1

The American Journal of Human Genetics 2026 Open access

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Authors: Irene González-Martínez, Estefanía Cerro-Herreros, Marc Carrascosa-Sàez, Andrea García-Rey, Diego Piqueras-Losilla, Anna Colom-Rodrigo, Nerea Moreno, Mouli Chakraborty, Aline Huguet-Lachon, Anchel González‐Barriga, Neia Naldaiz-Gastesi, Martxel Dehesa
+10 more Ana Díaz-Maqueda, Nuria Barquero, Miguel A. Varela, Adolfo López de Munain, ramon eritja, Geneviève Gourdon, Arturo López Castel, M. Pérez-Alonso, Beatriz Llamusí, Rubén Artero
DOI: 10.1016/j.ajhg.2026.01.016
Cited by: 3
References: 76

Abstract

and DMSXL mice and human myoblasts), increasing MBNL1 levels, correcting mis-splicing, improving muscle strength, and reducing myotonia. They also exhibited efficient biodistribution to skeletal muscle, a critical DM1-affected tissue. In vitro toxicology indicated a favorable safety profile with minimal immune or renal toxicity. The antimiR mechanism was conserved in rat and pig fibroblasts. Overall, two lead antimiRs emerged as promising therapeutic candidates for DM1, with improved pharmacokinetics, tissue targeting, and safety, supporting the potential of microRNA-based approaches to correct key molecular defects in this disorder.

Fields of Study & Subjects

Genetic Neurodegenerative Diseases Amyotrophic Lateral Sclerosis Research RNA Research and Splicing

Publication details

Journal / source
The American Journal of Human Genetics
Publisher
Elsevier BV
Volume
113
Issue
3
Pages
529–547
Publication date
20 February 2026
Language
EN