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Recent success of mRNA-based COVID-19 vaccines have bolstered the strength of nucleic acids as a therapeutic platform. The number of new clinical trial candidates is skyrocketing with the potential to address many unmet clinical needs. Despite advancements in other aspects, the systemic delivery of nucleic acids to target sites remains a major challenge. Thus, nucleic acid based therapy has yet to reach its full potential. In this review, we shed light on a select few prospective technologies that exhibit substantial potential over tradi