Fig. 4

Development and modification strategies for mRNA-LNP cancer vaccines. A Neoantigens can be identified and validated by whole genome sequencing, RNA sequencing or protein expression from normal and tumor tissues. Validated neoantigens can be utilized for the design of mRNA therapeutics, which may be delivered using LNPs. B The different neoantigen mRNAs could be linked tandemly to be synthesized and incorporated into LNPs for delivery as a personalized cancer vaccine. Co-stimulatory molecules, such as IL-12 and IL-27, may be co-delivered to activate immune cells. Other co-stimulatory molecules could include tumor suppressor genes like PTEN and p53 to induce cancer death, adjuvants like STING^V155M and glycolipid to activate CD8⁺ cells or invariant Natural Killer T (iNKT) cells, or macrophage polarization factors like IRF5 and IKKβ to induce M1 cell polarization. Surface modifications can be made to the LNPs, such as the addition of polysaccharides to induce immune response or the inclusion of endosome escape molecules to enhance mRNA release into the cytosol for expression