Design and development of mRNA and self-amplifying mRNA vaccine nanoformulations

The rapid evolution of mRNA vaccines, highlighted by Pfizer-BioNTech and Moderna's COVID-19 vaccines, has transformed vaccine development and therapeutic approaches. Self-amplifying mRNA (saRNA) vaccines, a groundbreaking advancement in RNA-based vaccines, offer promising possibilities for disease prevention and treatment, including potential applications in cancer and neurodegenerative diseases. This review explores the complex design and development of these innovative vaccines, with a focus on their nanoscale formulations that utilize nanotechnology to improve their delivery and effectiveness. It articulates the fundamental principles of mRNA and saRNA vaccines, their mechanisms of action, and the role of synthetic mRNA in eliciting immune responses. The review further elaborates on various nanoscale delivery systems (e.g., lipid nanoparticles, polymeric nanoparticles and other nanocarriers), emphasizing their advantages in enhancing mRNA stability and cellular uptake. It addresses advanced nanoscale delivery techniques such as microfluidics and discusses the challenges in formulating mRNA and saRNA vaccines. By incorporating the latest technologies and current research, this review provides a thorough overview of recent mRNA and saRNA nanovaccines advancements, highlighting their potential to revolutionize vaccine technology and broaden clinical applications.