Abstract

THE MRNA VACCINE: A COMPREHENSIVE REVIEW OF DEVELOPMENT, ADVANCED TECHNOLOGIES, THERAPEUTIC APPLICATIONS, AND SAFETY CONSIDERATIONS

Bhumil Varmora, Harsh Parmar, Vedant Patel, Advait Kushwah, Janki Patel*

Abstract

Messenger RNA (mRNA)-based therapeutics constitute a rapidly advancing and promising medical platform, recognized for its outstanding safety profile and non-integrative characteristics within the host genome. Exogenous mRNA is generally synthesized through In Vitro Transcription (IVT), a process that is both highly scalable and swift; however, issues related to purity, stability, and cellular delivery (for instance, through Lipid Nanoparticles (LNPs)) continue to pose challenges. The efficacy of the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 vaccines has validated this platform, showcasing an efficacy rate exceeding 90%. mRNA vaccines function by being encapsulated within LNPs for targeted delivery to antigen-presenting cells (APCs). Once inside the cytoplasm, the mRNA—which includes a 5' Cap, UTRs, and a Poly(A) Tail—is translated into the target antigen. This antigen is subsequently presented on MHC molecules, which activates CD8+ cytotoxic T cells and CD4+ helper T cells, thereby establishing longterm immunological memory. In addition to infectious diseases (such as COVID-19, HIV, and Influenza), the therapeutic applications are expanding to include cancer vaccines (for example, AML and melanoma), gene replacement therapies (such as those for cystic fibrosis), and gene editing delivery systems (like CRISPR-Cas9). Future advancements are anticipated to focus on next-generation RNA technologies—such as self-regulating mRNA constructs that utilize riboswitches and UTR engineering—to facilitate precise, dose-dependent control over protein expression and to address existing limitations.

Keywords: mRNA-based therapeutics, Lipid nanoparticles (LNPs), In vitro transcription (IVT), mRNA vaccines, Gene therapy / Gene editing.