Why oligonucleotide drugs?
Synthetic oligonucleotides are the key factor in almost all molecular biological methodologies. They are used in PCR, reverse transcription, sequencing, gene editing, synthetic biology, cloning, single nucleotide polymorphism analysis, microarray, electrophoretic mobility analysis, and small RNA studies. Most of these technological advances require synthesized oligonucleotides of high quality, completeness, and purity.
The currently marketed oligonucleotide drugs are mainly chemically modified to improve the metabolic stability of nucleotide structure and reduce adverse reactions, for instance, the modification of phosphodiester bonds, ribose, nucleotide bases, or ribose-phosphate backbones. Compared with the traditional drug development model, the new generation oligonucleotide drugs have obvious advantages. Conventional small-molecule drug development requires a great deal of screening and optimization process while oligonucleotide drug candidates can be quickly screened based on the primary gene sequence, and then high-specificity lead compounds can be designed. In addition, the unique function mechanism of nucleotide drugs allows them to modulate target activities that are not recognized by small molecules, thus providing a wider range of clinical applications.
Classifications of oligonucleotide drugs
Antisense oligonucleotide (ASO), small interfering ribonucleic acid (siRNA), ribozyme, deoxyribozyme, etc. are all concluded as nucleotide drugs. Oligonucleotides can regulate gene expression through a series of processes such as RNA interference, ribonuclease-mediated degradation, splicing regulation, non-coding RNA inhibition, gene activation, and programmed genome editing. ASO and siRNA are recognized as the most commonly used gene regulation tools, which are widely used and have been developed as gene therapy drugs.
FDA approval
Over 20 years of research and clinical trials, 14 small nucleic acid-based drugs have entered the market by 2021. The FDA-approved oligonucleotide drugs are listed in the table below.
| Name | Category | Approval Date | Indications |
| Fomivirsen ( Vitravene） | ASO | 1998.08 | Cytomegalovirus Retinitis |
| Pegaptanib (Macugen) | aptamer | 2004.12 | Age-Related Macular Degeneration |
| Mipomersen (Kynamro） | ASO | 2013.01 | Homozygous Familial Hypercholesterolemia |
| Defibrotide (Defitelio) | Mixture of ss-DNA and ds-DNA | 2016.03 | Hepatic Veno-Occlusive Disease |
| Eleplinsen (ExondlysSI) | ASO | 2016.09 | Duchenne Muscular Dystrophy |
| Musinersen (Spinraza) | ASO | 2016.12 | Spinal Muscular Atrophy |
| Patisiran ( Onpattro) | siRNA | 2018.08 | Heterotrophic Transthyretin Amyloidosis |
| Nolersen ( Tegsedi) | ASO | 2018.01 | Hereditary Transthyretin Amyloidosis, Polyneuropathy |
| Givosiran (Givlaari) | siRNA | 2019.11 | Acute Hepatic Porphyrias |
| Golodirsen ( Vyondlys 53) | ASO | 2019.12 | Duchenne Muscular Dystrophy |
| Viltolarsen ( Viltepso） | ASO | 2020.08 | Duchenne Muscular Dystrophy |
| Umasiran (Oxluno） | siRNA | 2020.11 | Primary Hyperoxaluria Type 1 (PH1) |
| Inelisiran (LeqvioTM) | siRNA | 2021.12 | Hypercholesterolemia |
| Casimersen ( Amondys 45) | ASO | 2021.02 | Duchenne Muscular Dystrophy |
The above drugs are mostly used for genetic and rare diseases. At present, there are still a large number of oligonucleotide drugs in the research and clinical stage, indicating great prospects for future development.
BOC Sciences perspective
BOC Sciences also deems that oligonucleotide drugs have a broad market prospect. As a new category of gene therapy drugs, oligonucleotide drugs have been rapidly developed, providing hope for many rare or incurable diseases. However, the process of oligonucleotide drugs is complicated and it’s difficult to carry out impurity analysis. BOC Sciences will quicken its pace of innovation, aiming to provide high-quality nucleotide materials and custom synthesis support.
Reference:
1. Guo, C.F.; et al. Research progress of oligonucleotide analysis methods. Journal of Chinese Pharmaceutical Sciences. 2022, 57(11): 869-873.
Related Products:
| Name | CAS | Molecular Weight | Description |
| Fomivirsen Sodium | 160369-77-7 | 7122.04 | Fomivirsen sodium, an antisense 21 mer phosphorothioate oligonucleotide, is an antiviral drug used in cytomegalovirus retinitis (CMV) studies, including AIDS. |
| Pegaptanib Sodium | 222716-86-1 | 535.5 | Pegaptanib sodium is an RNA aptamer directed against vascular endothelial growth factor (VEGF)-165. |
Related Service:
| Services | Description | ||
| Custom Synthesis | BOC Sciences’ scientists are skilled in the latest methods in synthetic organic chemistry. |