Qamar Abuhassan
1* 
, Ahmed Aldulaimi
2, O. S. Waleed
3, Subbulakshmi Ganesan
4, V. Kavitha
5, Laxmidhar Maharana
6, Renu Sharma
7, Mutabar Latipova
8,9, Nazira Madatova
10, Doniyor Jumanazarov
11, Aseel Smerat
12,131 Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Jordan, Amman, 11942, Jordan
2 Department of Pharmacy, Al-Zahrawi University, Karbala, Iraq
3 Medical Laboratory Technique College, The Islamic University, Najaf, Iraq
4 Department of Chemistry and Biochemistry, JAIN (Deemed-to-be University), Bangalore, Karnataka, India
5 Department of Chemistry, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
6 Department of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
7 Department of Chemistry, University Institute of Sciences, Chandigarh University, Mohali, Punjab, India
8 University of Tashkent for Applied Sciences, Str. Gavhar 1, Tashkent 100149, Uzbekistan
9 National Research University TIIAME, Kori Niyoziy 39, Tashkent 100000, Uzbekistan
10 The Department of Pharmaceutical and Chemistry, Alfraganus University, Tashkent, 100190, Uzbekistan
11 Urgench State University, Kh. Alimdjan str. 14, Urgench 220100, Uzbekistan
12 Faculty of Educational Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
13 Centre for Research Impact and Outcome, Chitkara University, Punjab, India
Abstract
RNA vaccines represent a major advance in prophylactic and therapeutic vaccinology, largely due to the success of nucleoside-modified mRNA vaccines encapsulated in lipid nanoparticles (LNPs) during the COVID-19 pandemic. These platforms build on long-standing progress in RNA chemistry, immunology, and nanotechnology. This review concentrates primarily on molecular design (codon/sequence optimization, chemical modifications, and data-driven antigen selection) and delivery optimization (LNPs and emerging alternatives like virus-like particles, extracellular vesicles, and ligand-targeted systems). Clinical progress is highlighted through examples from oncology, including personalized neoantigen approaches, combination therapies, and immunopeptidomics-guided validation, as well as early preclinical work on tolerance induction and localized protein replacement. Overall, continued refinement of RNA sequence engineering and delivery systems positions these platforms as flexible tools for rapid-response vaccination and therapy, especially where fast antigen adaptation and scalable production are required.