Current landscape of clinical trials for mRNA-based therapeutics

Beyond coronavirus disease 2019 (COVID-19) vaccines, messenger RNA (mRNA)-based therapeutics have increasingly demonstrated potential across other treatment areas. To summarize the clinical research landscape for such products and provide valuable references for researchers working in related fields, mRNA clinical trials registered on ClinicalTrials.gov (CTg) and the Chinese Clinical Trial Registry (ChiCTR) up to June 7, 2025, were analyzed. Twelve key items, including registration number, study title, target disease, interventions, blinding, sponsor, phases, enrollment, funder type, study type and start date, and locations, were analyzed to describe trial characteristics. A total of 557 clinical trials of mRNA-based therapeutics were identified. Most of these studies were conducted in phases 0-3 (n = 412, 73.97%), primarily focusing on infectious diseases (n = 410, 73.61%), and predominantly open-label designs (n = 338, 60.68%). Interventional studies accounted for 85.82% (n = 478) of all registered trials. Industry sponsors were the primary source of funding (n = 299, 53.68%). Approximately 45.06% of the projects (n = 251) aimed to enroll 0-100 participants. Most of the studies involved mRNA vaccines (n = 507, 91.02%). Further, 22 trials investigated mRNA-based therapeutics for rare diseases. Among the newly registered projects in 2024 and 2025, the proportion of phase 0-1 trials significantly increased, accounting for 61.67% and 78.13%, respectively. The top three regions that conducted mRNA clinical studies were North America (n = 186; primarily the United States [n = 178]), Asia (n = 184; China [n = 72]), and Europe (n = 90), based on studies registered in both CTg and ChiCTR. Most mRNA products remain in preapproval clinical trials. Further phase 3 clinical evidence will be essential to support its broader application.