Since its discovery, mRNA technology has faced a long and arduous journey—plagued by instability and immunogenicity for decades. It was not until the 21st century that breakthroughs in mRNA synthesis, modification, and delivery technologies largely resolved these challenges, reviving mRNA technology from its低谷.

Traditional small-molecule drugs can bind to target proteins to exert therapeutic effects, but the number of druggable protein targets is limited and targeting is often poor. Biologics—such as monoclonal antibodies—can target a broader range of proteins and offer improved affinity and reduced toxicity through protein engineering. However, antibodies are structurally more complex and costly to produce. More importantly, both classes of drugs typically require 10–15 years for R&D and have complex manufacturing processes. In emergencies like the COVID-19 pandemic, such timelines are simply untenable.

In contrast, nucleic acid-based drugs do not bind directly to target proteins. Instead, they regulate gene expression through base-pairing complementarity and are delivered into cells via appropriate delivery systems. They can modulate both intracellular and extracellular proteins. Once the target gene sequence is identified, nucleic acid drug design is relatively straightforward—they are rapidly translated into proteins, shortening R&D timelines to 4–7 years, with naturally metabolized products and high safety profiles. For example, the SARS-CoV-2 genome sequence was published in January 2020; by December 2020, mRNA vaccines had received Emergency Use Authorization in the U.K.

Early nucleic acid research focused primarily on DNA technology. With breakthroughs in delivery and sequence modification, mRNA has demonstrated advantages over DNA:

• Rich target selection: Many challenging or intracellular proteins can be encoded by mRNA and secreted extracellularly, targeting receptors or the circulatory system.
• High efficiency: mRNA does not need to enter the nucleus—it only needs to reach the cytoplasm to initiate protein translation, unlike DNA which must enter the nucleus and transcribe into mRNA.
• Safety: mRNA does not integrate into the genome; it only transiently expresses the encoded protein with no cumulative toxicity. DNA and viral vectors carry risks of exogenous infection.
• Cost-effective: mRNA is easily synthesized through in vitro transcription, with low production costs and high batch manufacturing efficiency.

With these significant advantages, it is now a reality that "all pharmaceutical companies are paying attention to mRNA."