Nucleic acids are biological macromolecules, including DNA and RNA. These two kinds of molecules can be used for the prevention, diagnosis and treatment of diseases, which are nucleic acid drugs. Nucleic acid drugs include small interfering RNA(siRNA), small exciting RNA(saRNA), microRNA and messenger RNA(mRNA).
All kinds of common RNA and their functions
Source: Guotai Junan Securities Research
The appearance of small nucleic acid drugs makes it possible to actively design drug sequences to target silent disease genes. Compared with other drugs targeting proteins, small nucleic acid drugs have the advantages of short preclinical research and development cycle, rich candidate targets, high specificity, high efficiency and long-term effect.
The candidate targets are abundant and the indications are widely distributed.
Theoretically, any disease caused by over-expression of specific genes can be treated by small nucleic acid drugs, which provides rich candidate targets for the research and development of small nucleic acid drugs, including many targets that traditional drugs can’t become drugs.
Simple drug design and short research and development cycle.
Small nucleic acid drugs are the biggest benefit areas of genomics and functional genomics. The design of small nucleic acid drugs can realize the digital design of disease gene (mRNA) sequences directly, thus getting rid of the large-scale screening cycle of traditional drugs, enabling drug design to be carried out actively, and the success rate of research and development is relatively high.
Strong targeting specificity
Small nucleic acid drugs can regulate gene expression from the post-transcriptional level, can specifically act on the mRNA transcribed by the pathogenic gene, regulate the expression of the pathogenic gene from the upstream of the disease, and can achieve sequence specificity at the single base level, with the characteristics of "targeted" and "temporary solution". In addition, the continuous innovation of nucleic acid drug delivery system can effectively deliver nucleic acid drugs to target organs, and truly achieve targeted drug delivery.
Long-acting drug
On the whole, the effective action time of small nucleic acid drugs is longer than that of traditional small molecules and protein drugs. Taking siRNA drugs as an example, when the target mRNA is degraded, the RNA-induced silencing complex (RISC) can work circularly and participate in the next degradation of the target mRNA. In addition, the continuous innovation of chemical modification technology of nucleic acid drugs, including phosphate skeleton modification, glycosyl modification and base modification, can improve the stability and half-life of nucleic acid drugs, make the drug act longer, and greatly improve the compliance of patients with treatment. The long action cycle makes small nucleic acid drugs have competitive advantages in the fields of chronic diseases such as cardiovascular diseases.
At present, the main nucleic acid drugs listed in the world are antisense nucleic acid (ASO), small interfering RNA(siRNA) and nucleic acid aptamer. In addition to nucleic acid aptamers (which may exceed 30 nucleotides), nucleic acid drugs are usually oligonucleotides composed of 12~30 nucleotides, also known as oligonucleotide drugs. In addition, miRNA, ribozyme and deoxyribozyme also show great development value in the treatment of many diseases. Nucleic acid drugs have become one of the most promising fields in biomedical research and development.
Examples of approved nucleic acid drugs
Image source: Pharmaceutical Online
Compared with the existing small molecule and antibody drugs, small nucleic acid drugs have the advantages of fast target screening, high success rate of research and development, less drug resistance, wider therapeutic field and long-term effect, and have great development potential. Small nucleic acid drugs are expected to cover more indications, so their potential market scale is very broad. It is estimated that the global sales of small nucleic acid drugs will exceed 10 billion US dollars by 2025.
At present, a total of 14 small nucleic acid drugs have been approved for marketing in the world (three drugs were delisted in the early stage), including 9 ASO drugs, 4 siRNA drugs and 1 nucleic acid aptamer. After years of development, heavy products of small nucleic acid drugs have appeared, among which Nusinersen developed by Bojian and Ionis is the first drug used to treat spinal muscular atrophy in the world, and its global sales in 2021 reached US$ 1.951 billion, which is the highest-selling small nucleic acid drug at present. Inclisiran developed by Novartis and Alnylam is a long-acting lipid-lowering drug, which only needs to be injected twice a year, opening a new chapter in the application of small nucleic acid drugs to common chronic diseases. 
Shengnuo medicine The company has the exclusive delivery platform of polypeptide nanoparticles (PNP) in the world, and uses it to develop innovative biopharmaceutical drugs for a variety of disease indications, including oncology, fibrotic diseases and disorders, viral infections and metabolic diseases. At present, STP705, the core product, is the first candidate drug that has achieved positive clinical results in the field of oncology.
Aibo biology At present, the company’s pipeline covers the fields of infectious disease prevention and tumor immunity, among which the mRNA vaccine developed for COVID-19 has entered the international multi-center phase III clinical research and obtained the drug production license.
Agner biology The company has independent intellectual property rights of GalPET liver targeting RNAi and lipid nanoparticles (LNP) delivery core platform technology. In March, 2022, COVID-19 mRNA vaccine developed by Agner Bio and Ruibo Bio carried out Phase II clinical trial.
Ruibo biology Is a nucleic acid technology as the core, the company not only has a variety of chemically modified oligonucleotide drug production capacity and large-scale production base, but also can provide the whole industrial chain production and development services from plasmid manufacturing, raw materials and enzyme production, to mRNA production and LNP preparation and filling of mRNA vaccines.
Ruibo biology China is the main pioneer of small nucleic acid technology and small nucleic acid pharmacy, and four products are in the clinical research stage. According to the unsatisfied clinical needs, the pipeline of products under research is formed around many diseases such as liver disease, cardiovascular disease, metabolism, ophthalmology and rare diseases.
Shenxin biology Focus on the development of preventive and therapeutic mRNA vaccines and drugs. Nearly 5000 LNP libraries have been constructed, and LNP vectors suitable for different treatment scenarios have been screened, which has created excellent conditions for the continuous research and development of mRNA product pipelines. With its leading LNP delivery technology platform, we firmly believe that biology has built research and development pipelines in four major directions: infectious diseases, rare diseases, tumor therapeutic vaccines and tumor immunotherapy enhancers.
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