Significance The RNA delivery field is mostly focused on lipid nanoparticles (LNPs). Although promising, LNPs have several limitations with respect to pharmacokinetics, biodistribution, and toxicity. The mechanism of RNA charge-altering releasable transporters (CART) delivery and release is unique. It proceeds dynamically with a controllable change in physical properties. Differing from all mRNA delivery systems, a key attribute of CARTs is a charge-altering degradation mechanism, which transforms the initial polycationic CART into neutral byproducts, thereby enabling endosomal escape, release, and subsequent translation of the polyanionic mRNA cargo. With this study, we introduce a potentially general approach to therapeutic vaccination enabled by a dynamic drug-delivery system (mRNA-CART) and demonstrate its utility in suppressing tumor formation and in eliminating established tumors.