Based on its rapid expression, simple sequence composition, low immunogenicity, and flexible modification possibilities, in vitro synthesized mRNA has demonstrated strong potential as a candidate for gene therapy. Many efforts have been made to enhance its therapeutic efficacy and safety. Profiting from the development in pathogenesis and materials science, much progress has been achieved in mRNA-based therapy studies. Many mRNA-derived therapeutics including vaccines, antibodies, cytokines, and growth factors have emerged for the treatment of diverse diseases that have multiple modes of action. Novel delivery vectors with enhanced capacity, safety, and properties have been developed to meet the demands of mRNA delivery. Advanced strategies like library screening, environment interaction, and bio-inspiration materials have been used in the investigation process and produced valuable results. In this review, we summarize and discuss recent advances in mRNA-based gene therapy studies.