Publication date: Sep 09, 2025

Therapeutic nucleic acids, including small interfering RNA (siRNA), and antisense oligonucleotides (ASOs), targeting RNA viruses such as influenza A virus (IAV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV), play a crucial role in contemporary medicine. The primary goal of short oligonucleotide-based antivirals is to precisely inhibit viral mechanisms by interacting with viral RNA, thereby opening new avenues for infection treatment. RNA recently was also used to invent mRNA vaccine for different illness prevention. Therapeutic nucleic acids and mRNA vaccine attracted considerable attention during the COVID-19 pandemic due to the pressing necessity to develop an effective strategy to address this global threat. In addition to the advancement of therapeutic nucleic acids aimed at targeting respiratory viruses, the effective delivery of these molecules to infected cells is of paramount importance. Similarly, mRNA vaccine’s effectiveness also depends on effective delivery. This article offers a comprehensive summary and analysis of various delivery strategies, along with the challenges encountered in their development. Representative studies conducted in cellular models, model organisms, and human are presented for examination. Furthermore, the article explores future perspectives regarding the delivery of therapeutic nucleic acids and mRNA vaccines aimed at combating IAV, SARS-CoV-2, and RSV.

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