Dynamin 2 messenger RNA (DNM2 mRNA) (DNM2 mRNA)

Dynamin 2 (DNM2) mRNA encodes a ubiquitously expressed large GTPase that is essential for clathrin-mediated endocytosis, membrane remodeling, and cytoskeleton dynamics (Cowling et al., 2014). While DNM2 is vital for normal cellular processes, its overexpression or gain-of-function is a primary driver of pathology in several neuromuscular disorders, including centronuclear myopathies (CNM) and Charcot-Marie-Tooth disease (Tasfaout et al., 2017). In X-linked Myotubular Myopathy (XLMTM), the loss of MTM1 leads to an accumulation of DNM2, and reducing DNM2 levels has been shown to rescue the disease phenotype in various animal models (Buono et al., 2018). Consequently, DNM2 mRNA is targeted by antisense oligonucleotides (ASOs) designed to bind the transcript and trigger RNase H-mediated degradation, thereby lowering the concentration of the DNM2 protein. Although this approach showed promise in preclinical studies, clinical development has faced challenges regarding the benefit-risk profile and the potential for systemic toxicity associated with long-term DNM2 reduction (ClinicalTrials.gov, NCT04033159).

Other names

DNM2 transcriptDynamin-2 mRNADYN2 mRNA

Antisense oligonucleotide-mediated mRNA degradation