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This review article from Mohammad Chehelgerdi and Matin Chehelgerdi, in Molecular Cancer, focuses on the use of RNA-based treatments in the field of cancer immunotherapy. It begins by explaining the mechanisms of action and potential applications of mRNA vaccines, including their advantages over traditional vaccine techniques. The review examines the current state of mRNA vaccine technology and highlights future directions for its development. It then discusses the optimization of mRNA translation and stability, including the use of lipid nanoparticles and other delivery systems. The article analyzes the immunogenicity of mRNA and its paradoxical effects in cancer immunotherapy, emphasizing the importance of properly activating the innate immune system. Finally, the review explores the potential of self-amplifying mRNA vaccines for cancer immunotherapy and concludes with a comprehensive overview of clinical trials and future perspectives on the development of RNA-based treatments in cancer immunotherapy.