In 2026, small nucleic acids will experience a comprehensive explosion from 1 to 100.

From rare diseases to broad indications, from long-acting drug delivery with "once-every-six-months injections" to successive breakthroughs in extrahepatic delivery, this field is no longer just an ideal vision for scientists, but has become the main battleground for industrial competition. Capital, transactions, and clinical data are all heating up simultaneously, with the number of global pipelines increasing by over 450% compared to seven years ago.

In this global competition, Chinese enterprises stand out prominently. Nearly 40% of the world's small nucleic acid pipelines originate from China. Local companies such as Bowang Pharmaceutical, Ruibo Biotech, Shengyin Biotech, Jingyin Biotech, and Frontier Biotech have frequently appeared at the deal table, becoming indispensable participants in this wave of going global.

As some domestic enterprises have made the leap from "following in technology" to "running alongside globally and exporting outward", the industry is increasingly convinced that small nucleic acids may be one of the most promising sub-sectors for Chinese innovative drugs to "overtake on the curve".

Recently, Tongxieyi interviewed Chang Yan, the president of InnoMed, who, as the helmsman of a preclinical CRO company, has clients covering innovative molecular forms such as antibodies, radiopharmaceuticals, small nucleic acids, ADCs, and cell and gene therapies. His perception of the popularity of these fields is almost the most direct.

In the interview, Chang Yan placed the sudden rise of small nucleic acids in a larger context - the overall accumulation of China's innovative drug industry system. In her view, this is not an isolated narrative of a single industry, but an inevitable explosion brought about by a mature system. "It is a very promising major track that has emerged under the already accumulated innovative drug industry system in China."

On this basis, she also deeply analyzed the underlying driving forces behind the rise and explosion of small nucleic acids in China, incorporating the unique mechanisms of drugs, differences in research and development paradigms, and the construction of an innovative ecosystem.

Chang Yan said that from the perspective of technological essence, small nucleic acid development involves nucleotide synthesis, chemical modification, and other links, and still belongs to the field of chemistry. China has already laid a solid foundation in this area. "China's speed advantage, innovation quality, and the foundation accumulated in the early stage of chemical pharmaceuticals can be well reflected in the race."

The explosion of a niche market never arises out of thin air, but rather marks the long-awaited homecoming moment after the industry has gone through a long period of preparation.

01、Breakthrough and Promising Future of Small Nucleic Acids

The unique feature of small nucleic acid drugs, known as "third-generation therapies," lies in their direct action on the source of disease: messenger RNA (mRNA). They can prevent the synthesis of pathogenic proteins at the post-transcriptional stage. This novel drug design logic has opened up the possibility of attacking many targets that were once considered "undruggable.".

Chang Yan pointed out that compared to traditional small molecules, small nucleic acids exert their effects based on the nucleic acid sequence, and the mechanism is very straightforward - as long as the nucleic acid sequence can be delivered to the target site, there is no need to worry too much about subsequent efficacy; whereas small molecule drugs tend to distribute widely, making it difficult to precisely concentrate on the lesion, and they are prone to off-target effects, interfering with non-target proteins.

Meanwhile, compared to antibody drugs, which are limited to extracellular targets and powerless against intracellular targets, small nucleic acids naturally act on intracellular nucleic acid sequences, precisely filling the technological gap. Once delivery is overcome, all diseases with clear targets and well-defined mechanisms have the potential to be druggable.

Liang Zicai, Chairman and CEO of Reebio, once used a clever analogy to summarize this generational leap: If small molecules and antibodies represent the "analog signal" era of modern pharmaceuticals based on "protein three-dimensional recognition", then small nucleic acid pharmaceuticals represent the "digital signal" era based on "mRNA sequence recognition".

However, this highly potential therapy has not been smooth sailing in the two decades since its inception. Since the discovery of RNA interference mechanism in 1998 and the awarding of the Nobel Prize in 2006, the field of small nucleic acids has experienced ups and downs, with MNCs coming and going. The core of the problem lies in delivery.
In the interview, Chang Yan traced the journey from modest beginnings to explosive growth: "The development of small nucleic acids took a long time in the early stages, and they didn't gain much popularity. It wasn't until the mature GalNac intrahepatic targeted delivery technology emerged, with the first product hitting the market, that things changed. During this process, the certainty and advantages of targeted technology were recognized, and the development of targets for various chronic and infectious diseases reached new heights. ”

However, the targets within the liver are ultimately limited. Therefore, while the pipeline within the liver continues to advance, a significant amount of research and development efforts have shifted to areas outside the liver. Fat, kidneys, central nervous system, muscles, myocardial tissue... Various companies have successively established targeted delivery technology platforms with core characteristics.

Regarding the core delivery issue that constrains the development of the industry, Chang Yan believes that with the advancement of biotechnology, delivery itself is increasingly becoming more of an "engineering problem" rather than an original scientific problem in the absolute sense.

The breakthrough in delivery technology has laid a fundamental foundation for the boom of small nucleic acids, while clinical data is also providing the strongest support for this boom - the long-acting administration of small nucleic acids with "one injection every six months" demonstrates excellent stability and compliance.

With technological advancements, the application scenarios of small nucleic acids are continuously expanding. Chang Yan mentioned that apart from single-target pipelines, small nucleic acid drugs targeting dual or even multiple targets are currently under development, capable of addressing more complex diseases and clinical needs.

The promising future of small nucleic acids is transitioning from an ideal blueprint to a practical construction plan.  

02、The Foundational Strength of China's Small Nucleic Acid Industry

If the boom of small nucleic acids is likened to a long-distance race, the collective acceleration of Chinese enterprises relies not only on the judgment of technological directions, but also on the solid foundation accumulated over many years in a mature industrial system.

Chang Yan admitted that she had not heard too many problems and complaints from the pharmaceutical side in the field of small nucleic acids. "There are situations where there are technologies and ideas, but solutions cannot be quickly delivered, which are relatively rare." She pointed out that compared to the various pains encountered during the transition from small molecule to large molecule antibody production in the past, the transformation in the field of small nucleic acids is much smoother.

This smoothness is rooted in China's solid foundation in the innovative drug research and development industry system.

From a technical perspective, small nucleic acids still largely fall within the scope of small molecule chemistry, with processes such as nucleotide synthesis and chemical modification being traditional strengths in the chemical field. China has already accumulated profound expertise in the improvement and innovation of production processes in chemical pharmaceuticals, antibodies, CGT, and other fields.

In the early research stage, the sequence of small nucleic acids is directly designed to target human genes and targets, which leads to differences in the early research and development logic compared to traditional innovative drugs.

Chang Yan pointed out that in the early research and development stage of small nucleic acids, the core work lies in the production verification of newly developed targeted delivery technologies, and screening among different technological paths. The logic is similar to the ligand research and development of ADCs and nuclear drugs.

Meanwhile, due to sequence differences and species issues, experimental monkeys must be used in the early stages of small nucleic acid research to address PCC selection and confirmation, whereas traditional drugs often only require rodents at this stage to meet requirements.

Chang Yan believes that the ecosystem for small nucleic acids in China is rapidly established. Unlike nuclear medicine, which requires solving complex issues such as the import of radionuclides and the construction of a hospital nuclear medicine system, each link of small nucleic acids—from early sequence design, non-clinical evaluation to later commercial production—can quickly build corresponding capabilities and response speed based on the direction of research and development enterprises.

"The industry can quickly find a series of solutions, so that new tracks and new molecular forms can also achieve efficient R&D support and advancement, just like mature tracks."

"Even if some new problems may arise, they can be quickly resolved." Regarding this, she specifically cited bioanalysis as an example. The bioanalysis requirements for small nucleic acids are extremely high, and initially it may take 4 to 6 weeks to complete. However, once the industry becomes familiar with a type of delivery molecule, it can be incorporated into conventional bioanalysis methods, significantly improving efficiency.

03、Overtakes on the curve, the future is now

The evolutionary history of the pharmaceutical industry is essentially a generational transition in drug forms.

Small molecule drugs marked the beginning of modern pharmaceuticals, precisely intervening in protein function through chemical means, yet they are constrained by target accessibility and selectivity. Antibody drugs expanded the treatment frontier to extracellular targets, marking the second act, yet the intracellular world remains an insurmountable territory.

Nowadays, small nucleic acids are unveiling the third act with the logic of "genetic sequence recognition" - it is not a mere repair of the previous two generations, but a fundamental paradigm shift.

The narrative of China's innovative drug industry resonates precisely with this generational change.

In the field of traditional chemical drugs, China started late and has limited accumulation. The construction of original chemical molecule libraries takes decades, making the cost of catching up extremely high. In the era of antibodies, China achieved parallel development with other countries by leveraging its engineering capabilities. And when it comes to the era of small nucleic acids, a type of "digital signal" drug, China started almost simultaneously with the rest of the world.

From sequence design and chemical modification to the engineering iteration of delivery systems, from early raw material supply to non-clinical and clinical research, China possesses complete industrial capabilities and accumulated experience in every aspect. Coupled with the advantage of monkey resources in non-clinical research, as well as patient and efficiency advantages in clinical settings, these various advantages are combining to form a synergistic force.

Based on this, Chang Yan's judgment is concise and powerful: "In emerging fields, our advantages will be even more prominent. When the industrial ecosystem is already mature and a brand-new molecular field emerges, and every link has experience and capability in China - under the same conditions of capability, China's advancement speed is unparalleled."

Meanwhile, she holds great expectations for the future of small nucleic acids. In her view, with the continuous breakthroughs in extrahepatic delivery technology, the disease spectrum originally limited to intrahepatic targeting will be significantly expanded, and more and more "undruggable" targets are expected to be overcome by nucleic acid drugs.

"Perhaps in ten or twenty years, nucleic acid drugs will largely replace traditional small molecule drugs in the commercial sector," Chang Yan predicted. "That will be the ultimate vision of the epoch-making commercialization wave of nucleic acid drugs."

At the inaugural Global Conference on Pharmaceutical Innovation for China (CPIC 2026), held from July 22nd to 24th, Chang Yan will collaborate with Dr. Liang Zicai, Chairman and CEO of Ruibo Biotech, and Li Hao, CMO of Kanglong Chemical, to organize the "Global Conference on Small Nucleic Acid Drug Innovation". This event will bring together international cutting-edge and domestic innovative forces to promote innovative research and development.

This is not just a technical exchange, but also a gathering of industry consensus - allowing capital to see the true potential of China's small nucleic acid industry. At the same time, leveraging the global high-level conference platform, we will candidly examine the remaining shortcomings in the research and development of nucleic acid drugs, and forge a consensus on policy and industry support. The ultimate goal is to accelerate the research and development process of nucleic acid drugs, and promote more Chinese original pipelines towards international transactions and cooperation.