Research shows RNAi technology can now treat genetic diseases and cancer as well as various medical conditions through advanced biotechnology. Scientists use siRNA drugs as innovative treatments because they target specific diseases well while helping patients stay safe.
Market Prospects of siRNA Drugs
The medical system uses authorized siRNA drugs mainly to treat diseases that result from genetic and metabolic issues. The number of siRNA drugs progressing through clinical validation has grown to cover multiple disease areas including cancer and cardiovascular diseases as well as neurological and immune system disorders. The market for siRNA drugs increases at a fast rate. A market research report from QYResearch shows that the global siRNA drug market earned USD 1.59651 billion in 2023 with expected revenue of USD 12.89237 billion in 2030 at a 31.94% annual growth rate.
Applications of siRNA Drugs
Genetic Diseases: siRNA drugs hold immense potential in treating genetic disorders such as spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD).
Cancer: siRNA drugs have broad applications in cancer treatment, such as targeting tumor-associated genes to inhibit tumor cell proliferation and invasion.
Cardiovascular Diseases: siRNA drugs can regulate the expression of relevant genes to reduce lipid levels and improve vascular function, thereby preventing cardiovascular diseases.
Immune Diseases: siRNA drugs can modulate immune cell functions, alleviating autoimmune diseases such as rheumatoid arthritis and psoriasis.
Challenges in the development of siRNA drugs
siRNA molecules are inherently unstable, pro-inflammatory, unevenly distributed, and difficult to absorb, posing numerous challenges for drug development.
Delivery Systems: Due to their molecular structure and negative charge, siRNA molecules struggle to penetrate cell membranes and enter cells. Designing efficient delivery systems is one of the critical hurdles in siRNA drug development.
Delivery Efficiency and Specificity: Ensuring siRNA is efficiently delivered to target cells while acting only on specific cell types or tissues is essential for enhancing drug efficacy and reducing side effects.
Stability and Bioactivity of siRNA Molecules: siRNA molecules are prone to degradation, requiring them to maintain stability and activity within the body. Their degradation and inactivation can significantly impact therapeutic outcomes.
Immunogenicity and Toxicity: As foreign substances, siRNA molecules may trigger immune responses, leading to adverse effects. Balancing drug activity while minimizing immunogenicity and toxicity is a major area of research.
Drug Metabolism and Distribution: The metabolism and distribution characteristics of siRNA drugs require thorough investigation to ensure proper distribution and therapeutic effects within the body.
Clinical Translation: Transitioning from laboratory research to clinical application is a complex process involving extensive clinical trials and regulatory approvals, requiring solutions to numerous practical challenges.
Cost Issues: The manufacturing costs of siRNA drugs are relatively high. Reducing production costs is necessary to enable large-scale production and market accessibility.
Developability of siRNA Drugs
Improving the developability of siRNA drugs is a complex process involving optimization and innovation across multiple aspects, including immunogenicity, stability, efficacy, manufacturing, and biodistribution.
Immunogenicity
Chemical Modifications: Chemical modifications of siRNA nucleotides, ribose, and phosphate backbone, such as 2’OMe and 2′-F, can reduce the immunogenicity of siRNA.
Optimized Sequence Design: Selecting or designing sequences with lower immunogenicity and avoiding sequences similar to known immunogenic ones can minimize immune responses.
Novel Delivery Systems: New delivery technologies like GalNAc can lower the immunogenicity of siRNA while enhancing its targeting specificity.
Stability
Chemical Modifications: Chemical modifications such as 2’OMe and thiolation can improve siRNA’s stability and half-life in the body.
Delivery Systems: Delivery systems like lipid nanoparticles (LNPs) can protect siRNA from degradation by enzymes in the body, improving stability.
Efficacy
Optimized siRNA Sequences: Selecting or designing more effective siRNA sequences ensures precise targeting and silencing of the target gene.
Delivery Systems: Improving delivery systems to enhance siRNA’s ability to reach target cells can boost its efficacy.
Manufacturing
Optimized Production Processes: Developing more efficient production methods, such as large-scale synthesis techniques, can lower costs and increase yield.
Improved Purification Methods: More effective purification techniques can reduce losses during production and improve the purity and quality of siRNA.
Biodistribution
Targeted Delivery Systems: Targeted delivery systems, such as LNPs, can precisely deliver siRNA to specific tissues and organs, minimizing exposure to non-target tissues.
Bioengineering Adjustments: Bioengineering techniques can modify LNPs’ biodistribution, enabling organ-specific gene regulation.
In summary, these approaches can effectively enhance the developability of siRNA drugs, enabling them to realize greater potential in treating various diseases. However, optimization in each aspect requires careful consideration of multiple factors and thorough validation in preclinical and clinical trials.
| Challenge | siRNA | BOC Sciences Services |
| Immunogenicity | 2’OMe2’FTerminal overhang(s) | DNA/RNA Modification |
| Stability | 2’F/2’OMe patternPhosphorothioate5’-VinylphosphonateaexNAa | Oligonucleotide Conjugation Services |
| Potency | 2’F/2’OMe patternAsymmetric strand selection5’-VinylphosphonateDivalent siRNA | RNA Interference (RNAi) Services |
| Manufacturability | Solid-phase synthesisBiocatalytic synthesis | Oligonucleotides Services |
| Biodistribution | LNPGalNAcC16 or fatty acidsNovel conjugates | RNA Drug Delivery System |
Reference
Androsavich, John R. “Frameworks for transformational breakthroughs in RNA-based medicines.” Nature Reviews Drug Discovery (2024): 1-24.