In recent years, oligonucleotides have emerged as a novel class of molecules that provide drug development researchers with a wide array of opportunities to develop therapeutic drugs to treat a broad range of diseases. Oligonucleotide therapeutics are synthesized chemically using approaches such as solid-phase synthesis and phosphoramidite synthesis. These molecules have shown high target specificity and pharmacokinetics profile, due to which oligonucleotides have been used in therapy production. The oligonucleotide synthesis using advanced technology made it possible to generate genetic modifications, including gene-editing treatments, gene therapies, and tissue-specific nucleic acid bio-conjugates. Owing to the high target specificity, several oligonucleotide-based therapies have been approved by the FDA to treat a wide array of diseases. Despite therapeutic significance, the oligonucleotide synthesis market is fraught with challenges, such as a lack of purification and analytical clinicians. To overcome these challenges, several oligonucleotide synthesis market players are actively exploring technologies to modify oligonucleotides for use in different applications.
Recently Approved Oligonucleotides-Based Therapeutic Drugs
Currently, several clinical studies have shown that oligonucleotides are an effective and safe treatment modality due to their unique characteristics, such as high pharmacokinetic profile and high target specificity. Owing to its characteristics, more than 14 oligonucleotide-based therapies have been approved by the FDA to date. Oligonucleotide-based therapeutic drugs are available in different forms, including antisense oligonucleotides, anti-micro RNAs (anti-miRNAs), small hairpin RNAs (shRNA), and small interfering RNAs (siRNA).
Therapeutic Significances of Oligonucleotides
Over the last few decades, oligonucleotides have been employed for therapeutic properties. In most cases, oligonucleotides have been used for the inhibition of genes or protein expression. Some of the potential areas where oligonucleotides have been used as a therapeutic agent include:
▪ Cancer Treatment
Antisense oligonucleotides that specifically bind to mRNA and inhibit gene translation have become a novel therapeutic strategy for the treatment of several kinds of cancer. However, the effective transport and non-specific protein binding seem to be the main obstacles to their application in cancer therapy.
▪ Neurodegenerative Disorders
Huntington's disease (HD) is an autosomal illness caused by a mutation in a single allele. Oligonucleotides can be employed as an effective therapy to treat this disease condition. These therapeutic molecules can inhibit the production of the causative protein Huntington by targeting the altered messenger RNA (mRNA). Amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, and spinal muscular atrophy (SMA) can all be treated using oligonucleotide-based therapeutic drugs.
▪ Respiratory Disorders
Treatment for asthma and chronic obstructive pulmonary disease can involve the inhalation of oligonucleotides. These oligonucleotide-based drugs are specifically aimed at the lungs, and because of this, they have fewer adverse effects. Additionally, the duration of action extends since their absorption is often improved at the target region.
Current Challenges of Oligonucleotide Therapies
Oligonucleotide-based drugs have garnered significant attention as a potential therapeutic agent to treat diseases. However, the development of oligonucleotides poses several challenges that have to be overcome to use them at a wide scale. Some of the challenges that are faced during the development of oligonucleotide therapies development are as follows:
▪ Instability Issues
Oligonucleotide is highly unstable and easily degrades with enzymatic reactions and instant renal clearance. In an attempt to bring stability, several strategies have been developed by oligonucleotide synthesis market players to reduce unwanted bioactivity issues.
▪ Target Specificity
The unnecessary modification of the oligonucleotides, sugar motifs, and phosphate backbone may result in toxicity, resulting in low target specificity. Attaining high target specificity without affecting nearby proteins or non-targeted genes is challenging. The unintended off-target effects may limit the therapeutic potential of the oligonucleotides.
▪ High Production Cost
The production cost of oligonucleotide-based therapies is high and hinders the accessibility of the therapies to the population. Technological advances are required to reduce the cost of oligonucleotide-based drug development.
▪ Regulatory Concerns
In order to develop these novel therapies, oligonucleotide synthesis market players have to meet standard regulatory compliances. The complex regulatory compliance may create challenges for researchers in developing oligonucleotide-based therapies. However, regulatory authorities are paying attention to establishing flexibility in guidelines to accelerate the approval of these novel therapies.
With the challenges above, it is anticipated that as related technologies continue to advance and develop, oligonucleotide therapies—that are exemplified by small interfering RNA and antisense oligonucleotides—will undoubtedly spark a new wave in the pharmaceutical sector. Furthermore, it is poised to play a pivotal role in the third-generation pharmaceutical industry revolution, driven by the control of gene expression.
Top Market Players in Oligonucleotide Synthesis Market
The top oligonucleotide synthesis manufacturers are actively researching to overcome the challenges above and come up with advanced solutions. Some of the top market players that are actively finding ways to synthesize oligonucleotides are:
⬝ Agilent Technologies
⬝ Ajinomoto Bio-Pharma Services
⬝ Biosearch Technologies
⬝ CordenPharma
⬝ Integrated DNA Technologies
⬝ LGC
⬝ Lonza
⬝ Kaneka Eurogentec
⬝ Microsynth
⬝ Nitto Denko Avecia
⬝ Sigma Aldrich
⬝ STA Pharmaceutical.
⬝ Sumitomo Chemical
⬝ Thermo Fisher Scientific
⬝ TriLink Biotechnologies
Recent Milestones in the Oligonucleotide Synthesis Market
Oligonucleotides have become an indispensable backbone of the pharmaceutical industry for the development of advanced therapeutic drugs. To meet the growing demand for drugs, several oligonucleotide synthesis market players are actively enrolling in the industry to develop novel oligonucleotide synthesis solutions. Some of the recent developments that have taken place in the oligonucleotide synthesis market include the following:
⬝ In March 2023, AstraZeneca, Centre for Process Innovation, Novartis, and The University of Manchester entered into a strategic collaboration to facilitate large-scale manufacturing of oligonucleotides for a considerable investment of EUR 2.77 million.
⬝ In March 2023, Ansa Biotechnologies announced the successful de novo synthesis of the longest DNA oligonucleotide at 1,005 bases in a single synthesis.
Concluding Remarks
Oligonucleotides serve a vital role in the production of gene therapies that help to treat genetic disorders, chronic disorders, and cancer. The field of oligonucleotides is constantly changing, providing enormous opportunities to explore therapeutic applications. With the active participation of oligonucleotide synthesis market players and technological advances, researchers are able to bring intriguing theories associated with oligonucleotides into novel drugs that are specifically designed to treat diseases. In the future, these oligonucleotide delivery technologies might be used for the generation of broad applicable genetic therapies and vaccine development. Considering the upcoming advances to overcome challenges, the oligonucleotide synthesis market is anticipated to grow in the future.
