The April issue of 𝘕𝘈𝘙 𝘔𝘰𝘭𝘦𝘤𝘶𝘭𝘢𝘳 𝘔𝘦𝘥𝘪𝘤𝘪𝘯𝘦 features the article “CAG-targeting artificial miRNA with reduced off-target risk for efficient lowering of pathogenic polyglutamine proteins” authored by M. Pewińska-Kołodziejczak, A.Kotowska-Zimmer, Ł. Przybył, D. Wronka, A. Karlik, M. Smuszkiewicz, J. Balcerek, J. Suszyńska-Zajczyk, A. Piaszyk-Borychowska, M. Urbanek-Trzeciak, G. Sablok, E. Kozłowska, J. Podkowiński, A. Fiszer, P. Kozłowski, L. Handschuh, and M. Olejniczak.

In this study, the team developed highly selective CAG-targeting artificial miRNAs (amiRNAs) characterized by a significantly reduced risk of off-target effects. The lead therapeutic candidate, amiR136-13A, effectively lowered levels of mutant huntingtin in both cellular and animal models while demonstrating a very favorable safety profile. In addition, the therapy reduced levels of the short, pathological form of the huntingtin protein (HTT1a), which is considered an important factor in disease progression.

The results indicate that amiR136-13A may represent a promising therapeutic strategy not only for Huntington’s disease but also for other polyQ diseases. The authors emphasize that the applied approach enables selective silencing of the mutant allele with minimal impact on normal genes, thereby increasing the clinical potential of this gene therapy.

Congratulations to the entire team! 

Link to the publication: https://doi.org/10.1093/narmme/ugag023