RNA therapeutic approaches for dystrophic epidermolysis bullosa: a scoping review

Introduction: Dystrophic epidermolysis bullosa (DEB) is a severe genodermatosis caused by mutations in COL7A1, leading to deficient type VII collagen (C7). RNA-based therapeutics offer promising, mutation-specific alternatives. We aimed to map the preclinical and early translational research landscape of RNA-based therapies for DEB. Materials and methods: A scoping review was conducted per PRISMA-ScR guidelines (January 2005 to July 2025). Studies investigating antisense oligonucleotides (ASOs), RNA interference (RNAi), RNA trans-splicing (RTMs), or related strategies for DEB were included. Data were systematically charted and synthesized. Results: Twenty-three studies were included. Most were preclinical (95.7%), focusing on recessive DEB (RDEB). Dominant strategies were RTMs (43.5%) and ASOs (39.1%); RNAi comprised 13.0% of approaches. Efficacy assessments confirmed partial C7 restoration in vitro and in vivo, with levels reaching up to 36–56% in some ASO studies. Delivery was predominantly nonviral, yet reliance on simple models was common. Critical translational assessments, including long-term safety, immunogenicity, and delivery to intact skin, were largely absent. The sole Phase 1/2 clinical trial (NCT03605069) was terminated early, underscoring the translational gap. Conclusions: RNA-based strategies show robust preclinical proof-of-concept for partial C7 restoration. However, a significant gap persists due to delivery challenges, reliance on early-stage models, and lack of clinical validation. Future development must prioritize advanced delivery systems, rigorous safety profiling, and innovative trial designs to realize the therapeutic potential for DEB.