The evolution of therapeutics: A comparative review of small-molecule drugs and RNA-based medicines

Therapeutics, or medical treatments, encompass various approaches used to treat, control, or cure diseases and conditions. They can be categorized in many ways. Pharmacotherapy (also referred to as drug therapy) involves using chemical agents to treat diseases. Examples of drug therapies include small-molecule drugs and biologics. Biologics are large, complex molecules like vaccines, enzymes, and monoclonal antibodies. Advanced and targeted therapies are modern therapies with a high level of precision and target the actual cause of the disease at the genetic or molecular level. Gene therapy alters or replaces the genetic makeup of a patient's cells to correct the cause of a disease. Cellular therapy involves using the patient's cells, which are processed and reintroduced into the body. Examples include CAR-T cell therapy and stem cell therapy for regenerative medicine. Immunotherapy causes activation or suppression of the patient's immune system against diseases like cancer. RNA-based therapies can consist of antisense oligonucleotides, small single-stranded DNA, or RNA molecules capable of modulating gene expression and addressing disease-causing targets, such as transcription factors and other traditionally undruggable proteins, that lack a binding pocket accessible to small molecules. This review is about the comparison between small molecule drugs as a traditional yet effective approach and RNA therapeutics as an evolving and modern approach. Unlike prior reviews that treat these platforms largely in isolation, this work provides a direct, parameter-by-parameter comparison spanning mechanism, delivery, manufacturing, regulatory pathway, and cost, alongside a synthesis of documented late-stage failures and the patent landscape shaping clinical translation, with the aim of helping readers identify which modality, or combination of modalities, best fits a given disease context.