Small nucleic acid drugs are a class of short-chain nucleic acid molecules composed of a dozen to several dozen nucleotides, which interfere with messenger RNA.RNA（mRNA) expression, regulating the production of pathogenic proteins at the source. Unlike traditional small-molecule drugs and antibody drugs that directly target proteins, small nucleic acid drugs act more like modifications.“Production Drawings”, precise intervention at the post-gene transcription stage brings three disruptive advantages: First, the range of targets is greatly expanded. Theoretically, any known sequence of pathogenic genes can become drug targets, overcoming many traditional“Undruggable”Targets; secondly, the efficacy is long-lasting, allowing for administration once every six months or even once a year, significantly improving patient compliance; thirdly, the R&D pathway is more straightforward, as designing drugs based on known gene sequences is more predictable than analyzing complex protein structures.

According to the mechanism of action and structure,Small nucleic acid drugs include RNAi drugs (siRNA), antisense oligonucleotides (ASO), microRNA (miRNA), small activating RNA (saRNA), and nucleic acid aptamers, among other types. Among them,ASOAndsiRNAAre currently the two most technically mature and widely applied categories.

As of2025Year12Month, globally there are already29A small nucleic acid drug has been approved for marketing (counted by generic name). Its development process was not achieved overnight, but rather throughRare Genetic DisordersAs a breakthrough, after verifying the technical feasibility and significant clinical value, and with the maturity of key technologies such as delivery systems, it gradually moves towards a large patient base.Chronic Disease FieldForging ahead with great momentum, achieving a revolutionary expansion in the field of treatment.

• Phase One: Rare Disease Breakthrough, Verifying Platform Feasibility and Clinical Value
  
  

The early development of small nucleic acid drugs wisely chose the field of rare genetic diseases, where the pathogenic genes are well-defined and unmet medical needs are urgent. These diseases are usually caused by a single gene defect, making them suitable for small nucleic acid drugs.“One-on-One”Provides an ideal scenario for precise intervention. At the same time, drugs targeting rare diseases enjoy policy benefits such as orphan drug designation, which can accelerate the listing process and enable companies to quickly validate their technology platforms.

At this stage, a number of milestone drugs emerged. For instance,Nusinersen (Nusinersen）As the world's first treatment for spinal muscular atrophy (SMA) ofASODrugs, through ingenious regulationSMN2Gene Splicing, Enhancing FunctionalitySMNThe expression of the protein has completely transformed the treatment landscape of this fatal genetic disease and once set a sales record, demonstrating the extraordinary commercial potential of small nucleic acid drugs. Similarly, the treatment of Duchenne Muscular Dystrophy (DMD) ofEteplirsen（Eteplirsen）Although the efficacy of these drugs is controversial, they have confirmed the possibility of achieving targeted therapy in the human body through an exon-skipping strategy.

These successes in the field of rare diseases have not only brought hope to patients but also completed the preliminary validation of the mechanism of action, safety, and production system of small nucleic acid drugs, laying a solid scientific and industrial foundation for subsequent expansion.

• Phase Two: Technical Inflection Point——Liver-Targeted Delivery Matures, Opening the Door to Chronic Diseases
  

The biggest bottleneck for small nucleic acid drugs expanding to common diseases lies inDelivery. How to safely and efficiently deliver fragile macromolecular nucleic acids to target tissue cells? The breakthrough in solving this difficult problem began withN-N-Acetylgalactosamine (GalNAc) Coupling TechnologyMaturity and Application.GalNAcCan bind to the highly expressed surface of liver cellsASGPRReceptor-specific binding, achievingsiRNAEfficient and precise liver-targeted delivery.

This technological inflection point is highly significant, as it will impact the liver——This metabolic and synthetic hub——Has become the first common disease that small nucleic acid drugs can systematically overcome“Main Battlefield”The success of liver targeting has directly led to a series of blockbuster drugs in the cardiovascular metabolism field.

• Phase Three: Advancing into Core Chronic Diseases, Demonstrating Disruptive Treatment Advantages
  

InGalNAcWith technology as the engine, small nucleic acid drugs have quickly emerged in the field of cardiovascular metabolism, the largest chronic disease area, showcasing their core advantages.“Long-acting”Displayed to the fullest extent.

Inclisiran (Inclisiran）It is the most brilliant star among them, as the first to target a common chronic disease (hypercholesterolemia).siRNADrug, it targetsPCSK9Genes, can achieveOnly twice subcutaneous injection per year, it can persistently and effectively reduce low-density lipoprotein cholesterol (LDL-C). This breaks the traditional pattern of daily medication or biweekly antibody injections, achieving chronic disease management.“Ultra-long-acting”Paradigm shift, patient compliance has made a qualitative leap. (Two Shots a Year, Ultra-Long-Acting Lipid-Lowering Drug "Inclisiran": A Brilliant New Star in Small Nucleic Acid DrugsStar）

Closely following, targetedAPOC3ThePulesran(Four times a year) andAoleize Sheng, it has demonstrated the same target for severe hypertriglyceridemia,siRNAAndASODifferentiated exploration of different technical pathways. In other chronic disease fields, such asHypertension、Anticoagulation、Progress has also been made in metabolic diseases.

As delivery systems and chemical modification technologies continue to mature, the research and development of small nucleic acid drugs is fiercely competing around four core tracks.

Cardiovascular Field：This is currently the most commercially mature track, focusing on directions such as lipid-lowering, blood pressure reduction, and anticoagulation. Companies in China, such as Ribo Life Science and Hegia Bio, have pipelines that have entered the mid-to-late stages of clinical trials, among which...“One Shot Once a Year”The ultra-long-acting lipid-lowering drugs have become a target for competitive breakthroughs.

Weight Loss and Metabolism Field：InGLP-1After the drug craze, small nucleic acid drugs are seeking to become“Efficient Partner”Or develop a completely new mechanism. For example, targetingINHBEIsogenicsiRNAThe therapy aims to achieve more precise fat reduction, in conjunction withGLP-1Combined use may bring synergistic therapeutic effects.

Kidney and Complement Diseases：In view of the large patient population and the highly unmet clinical needs, this field is regarded as2026Potential Explosion Point in the Coming Years. Multiple companies in and outside of China have laid out plans for drugs targeting key points in the complement pathway, with critical clinical data readings imminent.

Neurological Diseases and Extrahepatic Delivery：This is the frontier with the highest technical barriers and also the most imaginative one. Breaking through the blood-brain barrier and achieving effective delivery to the central nervous system is the key to treating neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, and will also determine the ultimate ceiling of the small nucleic acid market.

Against the backdrop of increasingly robust policy support and industrial chain integration, a group of domestic innovative companies in China have rapidly emerged, establishing differentiated technology platforms and pipeline layouts.

InRibo Life ScienceFor example, it independently constructed liver-targetingRiboGalSTAR™, Extrahepatic TargetingRiboPepSTAR™And other delivery platforms, with pipelines covering multiple fields such as cardiovascular, metabolic, and renal diseases, have reached cooperation with international pharmaceutical companies to advance global development.Sino BiopharmWith itsLEAD™Extrahepatic Targeting Platform: Focusing on Precision Delivery to Fat, Muscle, and Other Tissues, with a Strategic Layout in Metabolic and Immune Diseases.Bowang PharmaceuticalsThen with itsRADS™Platform technology, developing with stronger activity and persistenceRNAMolecules, and reached a significant strategic cooperation with Novartis to jointly develop cardiovascularsiRNATherapy.

In addition, such asHedgehog BioMulti-platform delivery technology (MVIP、DDP）、RiboSinoFocusedRNAActivation (RNAa) Therapy,Antorna Life ScienceThe Bifunctional Gene Regulation PlatformDARGER™etc., have showcased the diverse innovations of companies in China in delivery technologies and mechanisms of action. These companies are not only focusing on liver-targeted therapies but also actively challenging themselves to deliver to extrahepatic tissues such as the central nervous system, kidneys, and muscles, gradually engaging in cutting-edge global competition.