FDA Approved Oligonucleotide Drugs

September 30, 2022

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 approved oligonucleotide drugs

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.

Oligonucleotides at BOC Sciences

Name	Category	CAT	MW
Nusinersen	ASO	1258984-36-9	7501.0
eteplirsen	ASO	1173755-55-9	10305.738
Trabedersen	ASO		5768.7
ISIS 329993	ASO
Inclisiran sodium	siRNAs	B1370-057828	17,284.72 Da
Lumasiran	siRNAs	1834610-13-7	16,340 Da
Cemdisiran	siRNAs	1639264-46-2	16782.53
Manusiran	siRNAs	2646704-10-9	14058.53
AS 1411	Aptamers	301636-59-9	8272.31
Emapticap pegol	Aptamers	1390630-22-4	472.5
ADR58	Aptamers
Egaptivon pegol	Aptamers	934868-74-3

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.