Programmable RNA therapeutics: converging vaccination and on-demand disease treatment via self-adaptive RNA platforms

RNA technology, most prominently messenger RNA (mRNA), has transformed vaccine development by enabling rapid, sequence-specific antigen design, scalable manufacturing, and transient protein expression. Its long-term significance, however, extends beyond prophylactic vaccination. This Perspective argues that mRNA should be conceptualised as a programmable therapeutic platform capable of integrating vaccination, immune modulation, and on-demand disease treatment. Current mRNA vaccines deliver predefined antigenic instructions, whereas emerging RNA systems, including self-amplifying RNA (saRNA), circular RNA, sequence-engineered mRNA, and targeted lipid nanoparticles (LNPs), may support more adaptable therapeutic functions. Such platforms could prime immunity, replace deficient proteins, encode antibodies, reprogramme immune cells, or induce antigen-specific tolerance. The concept of self-adaptive RNA-based therapeutics remains at an early stage and should not be overstated; most existing systems are programmable at the design stage rather than biologically autonomous after administration. Nonetheless, this conceptual position is no longer purely speculative: the first regulatory approval of a self-amplifying RNA vaccine and controlled-trial evidence of clinical benefit from a personalised neoantigen mRNA therapeutic in resected melanoma indicate that programmable RNA platforms are beginning to move from concept to clinical validation across both the prophylactic and therapeutic ends of the spectrum. Key challenges include tissue-specific delivery, expression control, innate immune activation, repeat dosing, safety assessment, regulatory classification, and equitable access. A self-adaptive RNA-based framework does not replace existing vaccines or biologics but extends them towards responsive, personalised, and temporally controlled therapy.