Fig. 1

Translating small nucleic acid-based pharmacotherapy from bench to clinic and back. The development of small nucleic acid drugs begins with the design of potential nucleic acid sequences tailored to target specific diseases. Researchers then screen these sequences to identify the most effective candidates. Once optimal sequences are identified, they undergo chemical modifications to increase their stability and reduce their toxicity. These modifications optimize the drug’s pharmacokinetic properties, increasing the viability of the drug for therapeutic use. The modified small nucleic acid sequences are then encapsulated in delivery vectors. This step is crucial, as it further increases the drug’s stability in vivo and ensures that it reaches the specific target organ effectively. Extensive in vitro and in vivo evaluations have been conducted to assess the efficacy, safety, and pharmacodynamics of the drug. These evaluations help refine drug candidates before they proceed to clinical trials. Promising drug candidates then enter clinical trials, where many patients are recruited. Medical staff meticulously recorded the responses of different subjects to the candidate drugs, noting any therapeutic effects or adverse reactions. The clinical data obtained are analyzed by researchers, often with the assistance of artificial intelligence, to obtain deeper insights into the drug’s performance. This analysis helps researchers understand the drug’s efficacy, safety profile, and potential areas for improvement. The interpreted data are fed back to the laboratory for further optimization of the drug. Researchers may tweak the chemical structure, modify the delivery vector, or make other adjustments to enhance the drug’s performance. This iterative process continues, ensuring that each cycle brings the drug closer to its optimal form. This cycle of design, testing, feedback, and optimization is repeated until the drug meets the desired standards of efficacy and safety, ultimately leading to its approval and use in clinical settings